949 resultados para Genes, Immunoglobulin Heavy Chain
Resumo:
The Commonwealth Department of Industry, Science and Resources is identifying best practice case study examples of supply chain management within the building and construction industry to illustrate the concepts, innovations and initiatives that are at work. The projects provide individual enterprises with examples of how to improve their performance, and the competitiveness of the industry as a whole.
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Objective: We hypothesize that chondrocytes from distinct zones of articular cartilage respond differently to compressive loading, and that zonal chondrocytes from osteoarthritis (OA) patients can benefit from optimized compressive stimulation. Therefore, we aimed to determine the transcriptional response of superficial (S) and middle/deep (MD) zone chondrocytes to varying dynamic compressive strain and loading duration. To confirm effects of compressive stimulation on overall matrix production, we subjected zonal chondrocytes to compression for 2 weeks. Design: Human S and MD chondrocytes from osteoarthritic joints were encapsulated in 2% alginate, pre-cultured, and subjected to compression with varying dynamic strain (5, 15, 50% at 1 Hz) and loading duration (1, 3, 12 h). Temporal changes in cartilage-specific, zonal, and dedifferentiation genes following compression were evaluated using quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The benefits of long-term compression (50% strain, 3 h/day, for 2 weeks) were assessed by measuring construct glycosaminoglycan (GAG) content and compressive moduli, as well as immunostaining. Results: Compressive stimulation significantly induced aggrecan (ACAN), COL2A1, COL1A1, proteoglycan 4 (PRG4), and COL10A1 gene expression after 2 h of unloading, in a zone-dependent manner (P < 0.05). ACAN and PRG4 mRNA levels depended on strain and load duration, with 50% and 3 h loading resulting in highest levels (P < 0.05). Long-term compression increased collagen type II and ACAN immunostaining and total GAG (P < 0.05), but only S constructs showed more PRG4 stain, retained more GAG (P < 0.01), and developed higher compressive moduli than non-loaded controls. Conclusions: The biosynthetic activity of zonal chondrocytes from osteoarthritis joints can be enhanced with selected compression regimes, indicating the potential for cartilage tissue engineering applications. © 2012 Osteoarthritis Research Society International.
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In the context of cultural and/or differential ‘normalisation’ of certain forms of drug use, this article describes two case-studies of heavy recreational drug users. The daily lives of these users blur the line between the legal and the illegal; their drug trading is generally as a consumer and ‘friend of a friend’ small dealer in the low-level market. In the first case, problems with management of employment, time and financial budgeting are described; in the second case, such management is accomplished. Discussion refers to: differences between the two in relation to resources and vulnerability to risks, and to leisure/pleasure cultures of hedonism. The research agenda should pay more attention to users who seek to maintain a legitimate lifestyle but who develop problems managing work and their drug-related leisure. Understanding the consumer demand and dealing activity of such users is important in trying to develop a fuller understanding of drug markets.
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The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.
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Carotenoids occur in all photosynthetic organisms where they protect photosystems from auto-oxidation, participate in photosynthetic energy-transfer and are secondary metabolites. Of the more than 600 known plant carotenoids, few can be converted into vitamin A by humans and so these pro-vitamin A carotenoids (pVAC) are important in human nutrition. Phytoene synthase (PSY) is a key enzyme in the biosynthetic pathway of pVACs and plays a central role in regulating pVAC accumulation in the edible portion of crop plants. Bananas are a major commercial crop and serve as a staple crop for more than 30 million people. There is natural variation in fruit pVAC content across different banana cultivars, but this is not well understood. Therefore, we isolated PSY genes from banana cultivars with relatively high (cv. Asupina) and low (cv. Cavendish) pVAC content. We provide evidence that PSY in banana is encoded by two paralogs (PSY1 and PSY2), each with a similar gene structure to homologous genes in other monocots. Further, we demonstrate that PSY2 is more highly expressed in fruit pulp compared to leaf. Functional analysis of PSY1 and PSY2 in rice callus and E. coli demonstrate that both genes encode functional enzymes, and that Asupina PSYs have approximately twice the enzymatic activity of the corresponding Cavendish PSYs. These results suggest that differences in PSY enzyme activity contribute significantly to the differences in Asupina and Cavendish fruit pVAC content. Importantly, Asupina PSY genes could potentially be used to generate new cisgenic or intragenic banana cultivars with enhanced pVAC content.
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Rapid urbanisation and resulting continuous increase in traffic has been recognised as key factors in the contribution of increased pollutant loads to urban stormwater and in turn to receiving waters. Urbanisation primarily increases anthropogenic activities and the percentage of impervious surfaces in urban areas. These processes are collectively responsible for urban stormwater pollution. In this regard, urban traffic and land use related activities have been recognised as the primary pollutant sources. This is primarily due to the generation of a range of key pollutants such as solids, heavy metals and PAHs. Appropriate treatment system design is the most viable approach to mitigate stormwater pollution. However, limited understanding of the pollutant process and transport pathways constrains effective treatment design. This highlights necessity for the detailed understanding of traffic and other land use related pollutants processes and pathways in relation to urban stormwater pollution. This study has created new knowledge in relation to pollutant processes and transport pathways encompassing atmospheric pollutants, atmospheric deposition and build-up on ground surfaces of traffic generated key pollutants. The research study was primarily based on in-depth experimental investigations. This thesis describes the extensive knowledge created relating to the processes of atmospheric pollutant build-up, atmospheric deposition and road surface build-up and establishing their relationships as a chain of processes. The analysis of atmospheric deposition revealed that both traffic and land use related sources contribute total suspended particulate matter (TSP) to the atmosphere. Traffic sources become dominant during weekdays whereas land use related sources become dominant during weekends due to the reduction in traffic sources. The analysis further concluded that atmospheric TSP, polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) concentrations are highly influenced by total average daily heavy duty traffic, traffic congestion and the fraction of commercial and industrial land uses. A set of mathematical equation were developed to predict TSP, PAHs and HMs concentrations in the atmosphere based on the influential traffic and land use related parameters. Dry deposition samples were collected for different antecedent dry days and wet deposition samples were collected immediately after rainfall events. The dry deposition was found to increase with the antecedent dry days and consisted of relatively coarser particles (greater than 1.4 ìm) when compared to wet deposition. The wet deposition showed a strong affinity to rainfall depth, but was not related to the antecedent dry period. It was also found that smaller size particles (less than 1.4 ìm) travel much longer distances from the source and deposit mainly with the wet deposition. Pollutants in wet deposition are less sensitive to the source characteristics compared to dry deposition. Atmospheric deposition of HMs is not directly influenced by land use but rather by proximity to high emission sources such as highways. Therefore, it is important to consider atmospheric deposition as a key pollutant source to urban stormwater in the vicinity of these types of sources. Build-up was analysed for five different particle size fractions, namely, <1 ìm, 1-75 ìm, 75-150 ìm, 150-300 ìm and >300 ìm for solids, PAHs and HMs. The outcomes of the study indicated that PAHs and HMs in the <75 ìm size fraction are generated mainly by traffic related activities whereas the > 150 ìm size fraction is generated by both traffic and land use related sources. Atmospheric deposition is an important source for HMs build-up on roads, whereas the contribution of PAHs from atmospheric sources is limited. A comprehensive approach was developed to predict traffic and other land use related pollutants in urban stormwater based on traffic and other land use characteristics. This approach primarily included the development of a set of mathematical equations to predict traffic generated pollutants by linking traffic and land use characteristics to stormwater quality through mathematical modelling. The outcomes of this research will contribute to the design of appropriate treatment systems to safeguard urban receiving water quality for future traffic growth scenarios. The „real world. application of knowledge generated was demonstrated through mathematical modelling of solids in urban stormwater, accounting for the variability in traffic and land use characteristics.
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Organizations adopt a Supply Chain Management System (SCMS) expecting benefits to the organization and its functions. However, organizations are facing mounting challenges to realizing benefits through SCMS. Studies suggest a growing dissatisfaction among client organizations due to an increasing gap between expectations and realization of SCMS benefits. Further, reflecting the Enterprise System studies such as Seddon et al. (2010), SCMS benefits are also expected to flow to the organization throughout its lifecycle rather than being realized all at once. This research therefore proposes to derive a lifecycle-wide understanding of SCMS benefits and realization to derive a benefit expectation management framework to attain the full potential of an SCMS. The primary research question of this study is: How can client organizations better manage their benefit expectations of SCM systems? The specific research goals of the current study include: (1) to better understand the misalignment of received and expected benefits of SCM systems; (2) to identify the key factors influencing SCM system expectations and to develop a framework to manage SCMS benefits; (3) to explore how organizational satisfaction is influenced by the lack of SCMS benefit confirmation; and (4) to explore how to improve the realization of SCM system benefits. Expectation-Confirmation Theory (ECT) provides the theoretical underpinning for this study. ECT has been widely used in the consumer behavior literature to study customer satisfaction, post-purchase behavior and service marketing in general. Recently, ECT has been extended into Information Systems (IS) research focusing on individual user satisfaction and IS continuance. However, only a handful of studies have employed ECT to study organizational satisfaction on large-scale IS. The current study will enrich the research stream by extending ECT into organizational-level analysis and verifying the preliminary findings of relevant works by Staples et al. (2002), Nevo and Chan (2007) and Nevo and Wade (2007). Moreover, this study will go further trying to operationalize the constructs of ECT into the context of SCMS. The empirical findings of the study commence with a content analysis, through which 41 vendor reports and academic reports are analyzed yielding sixty expected benefits of SCMS. Then, the expected benefits are compared with the benefits realized at a case organization in the Fast Moving Consumer Goods industry sector that had implemented a SAP Supply Chain Management System seven years earlier. The study develops an SCMS Benefit Expectation Management (SCMS-BEM) Framework. The comparison of benefit expectations and confirmations highlights that, while certain benefits are realized earlier in the lifecycle, other benefits could take almost a decade to realize. Further analysis and discussion on how the developed SCMS-BEM Framework influences ECT when applied in SCMS was also conducted. It is recommended that when establishing their expectations of the SCMS, clients should remember that confirmation of these expectations will have a long lifecycle, as shown in the different time periods in the SCMS-BEM Framework. Moreover, the SCMS-BEM Framework will allow organizations to maintain high levels of satisfaction through careful mitigation and confirming expectations based on the lifecycle phase. In addition, the study reveals that different stakeholder groups have different expectations of the same SCMS. The perspective of multiple stakeholders has significant implications for the application of ECT in the SCMS context. When forming expectations of the SCMS, the collection of organizational benefits of SCMS should represent the perceptions of all stakeholder groups. The same mechanism should be employed in the measurements of received SCMS benefits. Moreover, for SCMS, there exists interdependence of the satisfaction among the various stakeholders. The satisfaction of decision-makers or the authorized staff is not only driven by their own expectation confirmation level, it is also influenced by the confirmation level of other stakeholders‘ expectations in the organization. Satisfaction from any one particular stakeholder group can not reflect the true satisfaction of the client organization. Furthermore, it is inferred from the SCMS-BEM Framework that organizations should place emphasis on the viewpoints of the operational and management staff when evaluating the benefits of SCMS in the short and middle term. At the same time, organizations should be placing more attention on the perspectives of strategic staff when evaluating the performance of the SCMS in the long term.
Influence of organic matter in road deposited particulates in heavy metal accumulation and transport
Resumo:
The research study discussed in the paper investigated the influence of organic matter on heavy metal adsorption for different particle size ranges of build-up solids. Samples collected from road surfaces were assessed for organic matter content, mineral composition, particle size distribution and effective cation exchange capacity. It was found that the organic matter plays a key role in >75µm particles in the adsorption of Zinc, Lead, Nickel and Copper, which are generated by traffic activities. Clay forming minerals and metal oxides of Iron, Aluminium and Manganese was found to be important for heavy metal adsorption to <75µm particles. It was also found that heavy metals adsorbed to organic matter are strongly bound to particles and these metal ions will not be bio-available if the chemical quality of the media remains stable.
Resumo:
Rationale Emerging evidence suggests that the α4β2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR α4β2 subunit partial agonist varenicline (Chantix™), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518–12523, 2007) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655–663, 2011; McKee et al., Biol Psychiatry 66:185–190 2009). Objectives We present a randomized, double-blind, 16-week study in heavy-drinking smokers (n = 64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens. Results Varenicline significantly decreases alcohol consumption (χ 2 = 35.32, p < 0.0001) in smokers. Although varenicline has previously been associated with suicidality and depression, side effects were low in this study and declined over time in the varenicline treatment group. Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.