877 resultados para Diffusion of Innovation (DOI)
Resumo:
The timing of widespread continental emergence is generally considered to have had a dramatic effect on the hydrological cycle, atmospheric conditions, and climate. New secondary ion mass spectrometry (SIMS) oxygen and laser-ablation–multicollector–inductively coupled plasma–mass spectrometry (LA-MC-ICP-MS) Lu-Hf isotopic results from dated zircon grains in the granitic Neoarchean Rum Jungle Complex provide a minimum time constraint on the emergence of continental crust above sea level for the North Australian craton. A 2535 ± 7 Ma monzogranite is characterized by magmatic zircon with slightly elevated δ18O (6.0‰–7.5‰ relative to Vienna standard mean ocean water [VSMOW]), consistent with some contribution to the magma from reworked supracrustal material. A supracrustal contribution to magma genesis is supported by the presence of metasedimentary rock enclaves, a large population of inherited zircon grains, and subchondritic zircon Hf (εHf = −6.6 to −4.1). A separate, distinct crustal source to the same magma is indicated by inherited zircon grains that are dominated by low δ18O values (2.5‰–4.8‰, n = 9 of 15) across a range of ages (3536–2598 Ma; εHf = −18.2 to +0.4). The low δ18O grains may be the product of one of two processes: (1) grain-scale diffusion of oxygen in zircon by exchange with a low δ18O magma or (2) several episodes of magmatic reworking of a Mesoarchean or older low δ18O source. Both scenarios require shallow crustal magmatism in emergent crust, to allow interaction with rocks altered by hydrothermal meteoric water in order to generate the low δ18O zircon. In the first scenario, assimilation of these altered rocks during Neoarchean magmatism generated low δ18O magma with which residual detrital zircons were able to exchange oxygen, while preserving their U-Pb systematics. In the second scenario, wholesale melting of the altered rocks occurred in several distinct events through the Mesoarchean, generating low δ18O magma from which zircon crystallized. Ultimately, in either scenario, the low δ18O zircons were entrained as inherited grains in a Neoarchean granite. The data suggest operation of a modern hydrological cycle by the Neoarchean and add to evidence for the increased emergence of continents by this time
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Animal and human studies have demonstrated that early pain experiences can produce alterations in the nociceptive systems later in life including increased sensitivity to mechanical, thermal, and chemical stimuli. However, less is known about the impact of neonatal immune challenge on future responses to noxious stimuli and the reactivity of neural substrates involved in analgesia. Here we demonstrate that rats exposed to Lipopolysaccharide (LPS; 0.05 mg/kg IP, Salmonella enteritidis) during postnatal day (PND) 3 and 5 displayed enhanced formalin-induced flinching but not licking following formalin injection at PND 22. This LPS-induced hyperalgesia was accompanied by distinct recruitment of supra-spinal regions involved in analgesia as indicated by significantly attenuated Fos-protein induction in the rostral dorsal periaqueductal grey (DPAG) as well as rostral and caudal axes of the ventrolateral PAG (VLPAG). Formalin injections were associated with increased Fos-protein labelling in lateral habenula (LHb) as compared to medial habenula (MHb), however the intensity of this labelling did not differ as a result of neonatal immune challenge. These data highlight the importance of neonatal immune priming in programming inflammatory pain sensitivity later in development and highlight the PAG as a possible mediator of this process
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The applicability of ELISA kits was evaluated as an alternative to monitor bensulfuron-methyl and simetryn behavior in paddy water under intermittent (Plot 1) and continuous (Plot 2) irrigation schemes. Simetryn concentrations in both plots decreased exponentially from the peak of the first day. However, the simetryn kit systematically underestimated by a factor of 0.79 as compared to the GC method. Bensulfuron-methyl concentrations exhibited similar dissipation kinetics in paddy water and the drainage water. The bensulfuron-methyl kit was capable of distinguishing spatial variations of concentrations in the paddy field. The ELISA kits clearly indicated differences in the loss of both herbicides between the two plots and therefore may be useful for evaluating the water management practice of pesticide runoff control in paddy fields.
Resumo:
Thymine DNA glycosylase (TDG) functions in base excision repair, a DNA repair pathway that acts in a lesion-specific manner to correct individual damaged or altered bases. TDG preferentially catalyzes the removal of thymine and uracil paired with guanine, and is also active on 5-fluorouracil (5-FU) paired with adenine or guanine. The rs4135113 single nucleotide polymorphism (SNP) of TDG is found in 10% of the global population. This coding SNP results in the alteration of Gly199 to Ser. Gly199 is part of a loop responsible for stabilizing the flipped abasic nucleotide in the active site pocket. Biochemical analyses indicate that G199S exhibits tighter binding to both its substrate and abasic product. The persistent accumulation of abasic sites in cells expressing G199S leads to the induction of double-strand breaks (DSBs). Cells expressing the G199S variant also activate a DNA damage response. When expressed in cells, G199S induces genomic instability and cellular transformation. Together, these results suggest that individuals harboring the G199S variant may have increased risk for developing cancer.
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Most genome-wide association studies to date have been performed in populations of European descent, but there is increasing interest in expanding these studies to other populations. The performance of genotyping chips in Asian populations is not well established. Therefore, we sought to test the performance of widely used fixed-marker, genome-wide association studies chips in the Han Chinese population. Non-HapMap Chinese samples (n = 396) were genotyped using the Illumina OmniExpress and Affymetrix 6.0 platforms, whereas a subset also were genotyped using the Immunochip. Genotyped markers from the Affymetrix 6.0 and Illumina OmniExpress were used for full genome imputation based on the HapMap 2 JPT+CHB (Japanese from Tokyo, Japan and Chinese from Beijing, China) reference panel. The concordance between markers genotypes for the three platforms was very high whether directly genotyped or genotyped and imputed single nucleotide polymorphisms (SNPs; .99.8% for directly genotyped and .99.5% for genotyped and imputed SNPs, respectively) were compared. The OmniExpress chip data enabled more SNPs to be imputed, particularly SNPs with minor allele frequency .5%. The OmniExpress chip achieved better coverage of HapMap SNPs than the Affymetrix 6.0 chip (73.6% vs. 65.9%, respectively, for minor allele frequency .5%). The Affymetrix 6.0 and Illumina OmniExpress chip have similar genotyping accuracy and provide similar accuracy of imputed SNPs. The OmniExpress chip however provides better coverage of Asian HapMap SNPs, although its coverage of HapMap SNPs is moderate. © 2013 Jiang et al.
Resumo:
The values that gave rise to the ethos of public service broadcasting (PSB) almost a century ago, and which have provided the rationale for PSBs around the world across that time, are under question. This article argues that the process of reinvention of PSBs is enhanced through repositioning the innovation rationale for public service media (PSM). It is organized around a differentiation which is part of the standard repertoire of innovation studies – that between product, process and organizational innovation – as they are being practised by the two Australian PSBs, the Australian Broadcasting Corporation (ABC) and the Special Broadcasting Service (SBS). The article then considers the general problematics of innovation for PSBs through an analysis of the operations of the public value test in the context of European PSM, and its, to this stage, non-application in Australia. The innovation rationale is argued to be a distinctive via media between complementary and comprehensive roles for PSM, which in turn suggests an international, policy-relevant research agenda focusing on international circumstances in which the public broadcaster is not market dominant.
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Endoplasmatic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in trimming of peptides to an optimal length for presentation by major histocompatibility complex (MHC) class I molecules. Polymorphisms in ERAP1 have been associated with chronic inflammatory diseases, including ankylosing spondylitis (AS) and psoriasis, and subsequent in vitro enzyme studies suggest distinct catalytic properties of ERAP1 variants. To understand structure-activity relationships of this enzyme we determined crystal structures in open and closed states of human ERAP1, which provide the first snapshots along a catalytic path. ERAP1 is a zinc-metallopeptidase with typical H-E-X-X-H-(X)18-E zinc binding and G-A-M-E-N motifs characteristic for members of the gluzincin protease family. The structures reveal extensive domain movements, including an active site closure as well as three different open conformations, thus providing insights into the catalytic cycle. A K 528R mutant strongly associated with AS in GWAS studies shows significantly altered peptide processing characteristics, which are possibly related to impaired interdomain interactions.
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Introduction: Emergency department nurse practitioner services are one of the most frequently implemented service delivery models in Australian hospitals. This research examined factors influencing sustainability of this innovative service delivery model and offers some recommendations for future service integration. Background Many health service innovations have been implemented in an attempt to meet the growing demand for efficient, cost effective health care however, sustainability of many of these innovations has not been evaluated and is poorly understood. Aim The aim of the research was to identify factors that influence sustainability of emergency department nurse practitioner services and to operationalise a theoretical framework for evaluating innovation sustainability. Methodology The research used case study methodology. The case was emergency nurse practitioner services, and units of analysis were emergency department staff, emergency nurse practitioners and documents relating to nurse practitioner services. The data collection methods included, survey, one-on-one interviews, document analysis and telephone survey. Results This research shows that emergency nurse practitioner services partially comply with the factors of sustainability as described in the Sustainability of Innovation theoretical framework: Political, Organisational, Workforce, Financial and Innovation specific factors. Where services do not entirely meet the factors the existing benefits of the service may outweigh the barriers and other means of working around shortfalls are also implemented by staff to ensure patient safety. Conclusion The rapidly expanding emergency nurse practitioner service has been examined using case study methodology to find that certain factors may be threatening the sustainability of this health service innovation. Potentially an innovation may be sustained when only some factors are met in the short term, however, long term sustainability may be challenged if factors are not addressed and supported.
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The aim of this study was to evaluate the mechanical triggers that may cause plaque rupture. Wall shear stress (WSS) and pressure gradient are the direct mechanical forces acting on the plaque in a stenotic artery. Their influence on plaque stability is thought to be controversial. This study used a physiologically realistic, pulsatile flow, two-dimensional, cine phase-contrast MRI sequence in a patient with a 70% carotid stenosis. Instead of considering the full patient-specific carotid bifurcation derived from MRI, only the plaque region has been modelled by means of the idealised flow model. WSS reached a local maximum just distal to the stenosis followed by a negative local minimum. A pressure drop across the stenosis was found which varied significantly during systole and diastole. The ratio of the relative importance of WSS and pressure was assessed and was found to be less than 0.07% for all time phases, even at the throat of the stenosis. In conclusion, although the local high WSS at the stenosis may damage the endothelium and fissure plaque, the magnitude of WSS is small compared with the overall loading on plaque. Therefore, pressure may be the main mechanical trigger for plaque rupture and risk stratification using stress analysis of plaque stability may only need to consider the pressure effect.
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Rupture of atherosclerotic plaque is a major cause of mortality. Plaque stress analysis, based on patient-specific multisequence in vivo MRI, can provide critical information for the understanding of plaque rupture and could eventually lead to plaque rupture prediction. However, the direct link between stress and plaque rupture is not fully understood. In the present study, the plaque from a patient who recently experienced a transient ischaemic attack (TIA) was studied using a fluid-structure interaction method to quantify stress distribution in the plaque region based on in vivo MR images. The results showed that wall shear stress is generally low in the artery with a slight increase at the plaque throat owing to minor luminal narrowing. The oscillatory shear index is much higher in the proximal part of the plaque. Both local wall stress concentrations and the relative stress variation distribution during a cardiac cycle indicate that the actual plaque rupture site is collocated with the highest rupture risk region in the studied patient.
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Fluidised bed-heat pump drying technology offers distinctive advantages over the existing drying technology employed in the Australian food industry. However, as is the case with many other examples of innovations that have had clear relative advantages, the rates of adoption and diffusion of this technology have been very slow. "Why does this happen?" is the theme of this research study that has been undertaken with an objective to analyse a range of issues related to the market acceptance of technological innovations. The research methodology included the development of an integrated conceptual model based on an extensive review of literature in the areas of innovation diffusion, technology transfer and industrial marketing. Three major determinants associated with the market acceptance of innovations were identified as the characteristics of the innovation, adopter information processing capability and the influence of the innovation supplier on the adoption process. This was followed by a study involving more than 30 small and medium enterprises identified as potential adopters of fluidised bed-heat pump drying technology in the Australian food industry. The findings revealed that judgment was the key evaluation strategy employed by potential adopters in the particular industry sector. Further, it was evidenced that the innovations were evaluated against a predetermined criteria covering a range of aspects with emphasis on a selected set of attributes of the innovation. Implication of these findings on the commercialisation of fluidised bed-heat pump drying technology was established, and a series of recommendations was made to the innovation supplier (DPI/FT) enabling it to develop an effective commercialisation strategy.
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This study addresses four issues concerning technological product innovations. First, the nature of the very early phases or "embryonic stages" of technological innovation is addressed. Second, this study analyzes why and by what means people initiate innovation processes outside the technological community and the field of expertise of the established industry. In other words, this study addresses the initiation of innovation that occurs without the expertise of established organizations, such as technology firms, professional societies and research institutes operating in the technological field under consideration. Third, the significance of interorganizational learning processes for technological innovation is dealt with. Fourth, this consideration is supplemented by considering how network collaboration and learning change when formalized product development work and the commercialization of innovation advance. These issues are addressed through the empirical analysis of the following three product innovations: Benecol margarine, the Nordic Mobile Telephone system (NMT) and the ProWellness Diabetes Management System (PDMS). This study utilizes the theoretical insights of cultural-historical activity theory on the development of human activities and learning. Activity-theoretical conceptualizations are used in the critical assessment and advancement of the concept of networks of learning. This concept was originally proposed by the research group of organizational scientist Walter Powell. A network of learning refers to the interorganizational collaboration that pools resources, ideas and know-how without market-based or hierarchical relations. The concept of an activity system is used in defining the nodes of the networks of learning. Network collaboration and learning are analyzed with regard to the shared object of development work. According to this study, enduring dilemmas and tensions in activity explain the participants' motives for carrying out actions that lead to novel product concepts in the early phases of technological innovation. These actions comprise the initiation of development work outside the relevant fields of expertise and collaboration and learning across fields of expertise in the absence of market-based or hierarchical relations. These networks of learning are fragile and impermanent. This study suggests that the significance of networks of learning across fields of expertise becomes more and more crucial for innovation activities.
Packed bed bioreactor for the isolation and expansion of placental-derived Mesenchymal Stromal Cells
Resumo:
Large numbers of Mesenchymal stem/stromal cells (MSCs) are required for clinical relevant doses to treat a number of diseases. To economically manufacture these MSCs, an automated bioreactor system will be required. Herein we describe the development of a scalable closed-system, packed bed bioreactor suitable for large-scale MSCs expansion. The packed bed was formed from fused polystyrene pellets that were air plasma treated to endow them with a surface chemistry similar to traditional tissue culture plastic. The packed bed was encased within a gas permeable shell to decouple the medium nutrient supply and gas exchange. This enabled a significant reduction in medium flow rates, thus reducing shear and even facilitating single pass medium exchange. The system was optimised in a small-scale bioreactor format (160 cm2) with murine-derived green fluorescent protein-expressing MSCs, and then scaled-up to a 2800 cm2 format. We demonstrated that placental derived MSCs could be isolated directly within the bioreactor and subsequently expanded. Our results demonstrate that the closed system large-scale packed bed bioreactor is an effective and scalable tool for large-scale isolation and expansion of MSCs.
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Innovation is understood as the combination of existing ideas or the generation of new ideas into new processes, products and services, and widely viewed as the main driver of growth in contemporary economies. In the age of the knowledge economy, successful economic development is intimately linked to a country’s capacity to generate, acquire, absorb, disseminate, and apply innovation towards advanced technology products and services. This development approach is labelled as knowledge-based economic development and highly associated with a capacity embodied in a country’s national innovation ecosystem. The research reported in this paper aims to critically review the Australian innovation ecosystem in order to provide a better understanding on the potential impacts of policy and support mechanisms on the innovation and knowledge generation capacity. The investigation places Australia’s innovation system and national-level innovation support mechanisms under the microscope. The methodology of the study is twofold. Firstly, it undertakes a critical review of the literature and government policy documents to better understand the innovation policy and support mechanisms in the country. It, then, conducts a survey to capture Australian innovation companies’ perceptions on the role and effectiveness of the existing innovation incentive programs. The paper concludes with a discussion on the key insights and findings and potential policy and support directions of the country to achieve a flourishing knowledge economy.
Resumo:
A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) approximately 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for approximately 2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.