Targeting nuclear factor-kappa B to overcome resistance to chemotherapy

Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge in the treatment of cancer patients. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation, and evasion of apoptosis. Pre-clinical models have demonstrated that many chemotherapy drugs, such as platinum-based agents, antracyclines, and taxanes, promote the activation of the NF-κB pathway. NF-κB is a key transcription factor, playing a role in the development and progression of cancer and chemoresistance through the activation of a multitude of mediators including anti-apoptotic genes. Consequently, NF-κB has emerged as a promising anti-cancer target. Here, we describe the role of NF-κB in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signaling by pharmacological intervention will be addressed.

Elements of Better Assessment for the Improvement of Learning

Building a community of shared practice at the classroom level calls for clarity about the important assessment capabilities and dispositions of teachers, especially when teachers are expected to take a direct focus on learning. In this chapter, we present new ways of thinking about teachers’ assessment literacies, offering a formulation of better assessment for the improvement of learning, including three elements, namely (i) assessment criteria and standards; (ii) the teacher’s professional judgment; and (iii) social moderation. The potential of the first element lies in teachers’ classroom practices that deliberately embed assessment criteria and standards in pedagogy in productive ways. The second element involves the engagement of teachers and students in judgment practice, that develops the understanding that judgment involves more than the application of explicit or stated criteria. More fundamental is the matter of how teachers bring to bear stated features of quality and other intellectual and experiential resources in arriving at judgment. That is to say, they range across and orient to explicit (stated), tacit (unstated) and meta-criteria in judgment making. These insights have direct relevance to teachers’ efforts to develop students’ own evaluative experience, especially as this involves students working with stated features of quality for self-assessment and peer-assessment purposes. Further, practices for social moderation are discussed, giving examples of good practice in moderation, how teachers experience moderation and the potential benefits of various types.

The Fukushima nuclear power plant disaster and percetions of health risk communication : a case study

This case study was conducted to explore the perceptions of health risk messages sent by the Japanese Government following the Fukushima nuclear power plant disaster. The content of health risk messages from the Japanese Government and the Japanese national broadcaster (NHK) were analysed and semi-structured interviews were conducted with a sample of Tokyo residents. Initially, participants trusted these messages but as the crisis unfolded they became sceptical about the messages. Participants felt the messages did not communicate health risk information effectively because the messages were; not supported by evidence, inconsistent, delayed and changed over time. Despite widespread access to the internet, social media and mobile telephones, most participants relied on television news for information about the health risks. The Japanese Government urgently needs to re-build trust by engaging the community in the planning and development phases of health risk communication strategies.

Considering the economic value of natural design elements at city scale

With increasing signs of climate change and the influence of national and international carbon-related laws and agreements, governments all over the world are grappling with how to rapidly transition to low-carbon living. This includes adapting to the impacts of climate change that are very likely to be experienced due to current emission levels (including extreme weather and sea level changes), and mitigating against further growth in greenhouse gas emissions that are likely to result in further impacts. Internationally, the concept of ‘Biophilic Urbanism’, a term coined by Professors Tim Beatley and Peter Newman to refer to the use of natural elements as design features in urban landscapes, is emerging as a key component in addressing such climate change challenges in rapidly growing urban contexts. However, the economics of incorporating such options is not well understood and requires further attention to underpin a mainstreaming of biophilic urbanism. Indeed, there appears to be an ad hoc, reactionary approach to creating economic arguments for or against the design, installation or maintenance of natural elements such as green walls, green roofs, streetscapes, and parklands. With this issue in mind, this paper will overview research as part of an industry collaborative research project that considers the potential for using a number of environmental economic valuation techniques that have evolved over the last several decades in agricultural and resource economics, to systematically value the economic value of biophilic elements in the urban context. Considering existing literature on environmental economic valuation techniques, the paper highlights opportunities for creating a standardised language for valuing biophilic elements. The conclusions have implications for expanding the field of environmental economic value to support the economic evaluations and planning of the greater use of natural elements in cities. Insights are also noted for the more mature fields of agricultural and resource economics.

An exploration into retrofitting cities with natural design elements - learning from the city of Berlin, Germany

Natural design features in the built environment or biophilic elements are emerging as a potential response to the challenges of climate change, urbanisation and population pressures which have invited issues such as rising urban heat island effect, rising pollution, increased congestion, among others. This concept of living cities was made popular by Professor Tim Beatley in his book titled ‘Biophilic Urbanism’. Evidence of biophilic urbanism can be seen in some cities from around the globe since decoupling environmental pressures from future development is a priority on many agendas. Berlin is an example of a modern economy that has adopted an ecological sustainable development approach to reduce environmental degradation while driving innovation and employment.

The Six Core Elements of Business Process Management

The previous chapters gave an insightful introduction into the various facets of Business Process Management. We now share a rich understanding of the essential ideas behind designing and managing processes for organizational purposes. We have also learned about the various streams of research and development that have influenced contemporary BPM. As a matter of fact, BPM has become a holistic management discipline. As such, it requires that a plethora of facets needs to be addressed for its successful und sustainable application. This chapter provides a framework that consolidates and structures the essential factors that constitute BPM as a whole. Drawing from research in the field of maturity models, we suggest six core elements of BPM: strategic alignment, governance, methods, information technology, people, and culture. These six elements serve as the structure for this BPM Handbook.

H2-O2 porous fuel injection in a radical farming scramjet

This paper reports on the experimental testing of oxygen compatible ceramic matrix composite porous injectors in a nominally two-dimensional hydrogen fuelled and oxygen enriched radical farming scramjet in the T4 shock tunnel facility. All experiments were performed at a dynamic pressure of 146 kPa, an equivalent flight Mach number of 9.7, a stagnation pressure and enthalpy of 40MPa and 4.3 MJ/kg respectively and at a fuelling condition that resulted in an average equivalence ratio of 0.472. Oxygen was pre-mixed with the fuel prior to injection to achieve enrichment percentages of approximately 13%, 15% and 17%. These levels ensured that the hydrogen-oxidiser mix injected into the engine always remained too fuel rich to sustain a flame without any additional mixing with the captured air. Addition of pre-mixed oxygen with the fuel was found to significantly alter the performance of the engine; enhancing both combustion and ignition and converting a previously observed limited combustion condition into one with sustained and noticeable combustion induced pressure rise. Increases in the enrichment percentage lead to further increases in combustion levels and acted to reduce ignition lengths within the engine. Suppressed combustion runs, where a nitrogen test gas was used, confirmed that the pressure rise observed in these experiments as attributed to the oxygen enrichment and not associated with the increased mass injected.

Biophilic urbanism : harnessing natural elements to enhance the performance of constructed assets

Creating climate resilient, low-carbon urban environments and assets is a policy goal of many governments and city planners today, and an important issue for constructed asset owners. Stakeholders and decision makers in urban environments are also responding to growing evidence that cities need to increase their densities to reduce their footprint in the face of growing urban populations. Meanwhile, research is highlighting the importance of balancing such density with urban nature, to provide a range of health and wellbeing benefits to residents as well as to mitigate the environmental and economic impacts of heavily built up, impervious urban areas. Concurrently achieving this suite of objectives requires the coordination and cooperation of multiple stakeholder groups, with urban development and investment increasingly involving many private and public actors. Strategies are needed that can provide ‘win-win’ outcomes to benefit these multiple stakeholders, and provide immediate benefits while also addressing the emerging challenges of climate change, resource shortages and urban population growth. Within this context, ‘biophilic urbanism’ is emerging as an important design principle for buildings and urban areas. Through the use of a suite of natural design elements, biophilic urbanism has the potential to address multiple pressures related to climate change, increasing urban populations, finite resources and human’s inherent need for contact with nature. The principle directs the creation of urban environments that are conducive to life, delivering a range of benefits to stakeholders including building owners, occupiers and the surrounding community. This paper introduces the principle of biophilic urbanism and discusses opportunities for improved building occupant experience and performance of constructed assets, as well as addressing other sustainability objectives including climate change mitigation and adaptation. The paper presents an emerging process for considering biophilic design opportunities at different scales and highlights implications for the built environment industry. This process draws on findings of a study of leading cities internationally and learnings related to economic and policy considerations. This included literature review, two stakeholder workshops, and extensive industry consultation, funded by the Sustainable Built Environment National Research Centre through core project partners Western Australian Department of Finance, Parsons Brinckerhoff, Townsville City Council CitySolar Program, Green Roofs Australasia, and PlantUp.

Technoeconomic analysis of renewable aviation fuel from microalgae,Pongamia pinnata, and sugarcane

Technoeconomic analysis of renewable aviatin fuels has not been widely considered, despite the increasing global attention that the field has received. We present three process models for production of aviation fuel from microalgae, Pongamia pinnata, and sugarcane molasses. The models and assumptions have been deposited on a wiki (http://qsafi.aibn.uq.edu.au) and are open and accessible to the community. Based on currently available long-term reputable technological data, this analysis indicates that the biorefinieries processing the microalgae, Pongamia seeds, and sugarcane feedstocks would be competitive with crude oil at $1343, $374, and $301/bbl, respectively. Sensitivity analyses of the major economic drivers suggest technological and market developments that would bring the corresponding figures down to $385, $255, and $168/bbl. The dynamic nature of the freely accessible models will allow the community to track progress toward economic competitiveness of aviation fuels from these renewable feedstocks.

Sweet sorghum : opportunities for a new, renewable fuel and food industry in Australia

Sweet sorghum is receiving significant global interest as an agro-industrial crop because of its capacity to co-produce energy, food, and feed products in integrated biorefineries. This report assesses the opportunities to develop a sweet sorghum industry in Australia, reports on research demonstrating the production of energy, food, and feed products, and assesses the potential economic and sustainability benefits of sweet sorghum biorefineries in the Australian context.

Mini-scale method for nuclear run-on transcription assay in plants

We present a mini-scale method for nuclear run-on transcription assay. In our method, all the centrifuge steps can be carried out by using micro-tubes for short time (5 min each) throughout the process, including isolation of transcriptionally active nuclei and purification of labeled RNA after synthesis of RNA in isolated nuclei. The assay can be performed using a small amount of plant tissue, which enables analysis of developmental changes in transcriptional status of given genes in a single individual plant. Successful results were obtained using the tissues of flower and leaf of petunia and embryo of pea, suggesting that the method is potentially applicable to a variety of plant tissues.

Developmentally and transgene regulated nuclear processing of primary transcripts of chalcone synthase A in petunia

The introduction of chalcone synthase A transgenes into petunia plants can result in degradation of chalcone synthase A RNAs and loss of chalcone synthase, a process called cosuppression or post-transcriptional gene silencing. Here we show that the RNA degradation is associated with changes in premRNA processing, i.e. loss of tissue specificity in transcript cleavage patterns, accumulation of unspliced molecules, and use of template-specific secondary poly(A) sites. These changes can also be observed at a lower level in leaves but not flowers of nontransgenic petunias. Based on this, a model is presented of how transgenes may disturb the carefully evolved, developmentally controlled post-transcriptional regulation of chalcone synthase gene expression by influencing the survival rate of the endogenous and their own mRNA.

The binding of nuclear factors to the as-1 element in the CaMV 35S promoter is affected by cytosine methylation in vitro

Transcriptional gene silencing (TCS) is often associated with an increased level of cytosine methylation in the affected promoters. The effect of methylation of the cauliflower mosaic virus (CaMV) 35S promoter sequence on its binding to factors present in the nuclei was analyzed by electrophoretic mobility shift assays using extracts of petunia flowers. Specific DNA-protein interactions were detected in the region of the CaMV 35S promoter that contains the as-1 element and the region between -345 and -208. The binding of protein factor(s) to the as-1 element was influenced by cytosine methylation, whereas the binding to the region between -345 and -208 was unaffected. The results suggest that cytosine methylation of the as-1 element potentially affects the activity of the CaMV 35S promoter. © Georg Thieme Verlag KG Stuttgart.

The construction of social identity in newly recruited nuclear engineering staff : a longitudinal study

This study examines the process by which newly recruited nuclear engineering and technical staff came to understand, define, think, feel and behave within a distinct group that has a direct contribution to the organization's overall emphasis on a culture of reliability and system safety. In the field of organizational behavior the interactive model of social identity formation has been recently proposed to explain the process by which the internalization of shared norms and values occurs, an element critical in identity formation. Using this rich model of organizational behavior we analyzed multiple sources of data from nine new hires over a period of three years. This was done from the time they were employed to investigate the construction of social identity by new entrants entering into a complex organizational setting reflected in the context of a nuclear facility. Informed by our data analyses, we found support for the interactive model of social identity development and report the unexpected finding that a newly appointed member's age and level of experience appears to influence the manner in which they adapt, and assimilate into their surroundings. This study represents an important contribution to the safety and reliability literature as it provides a rich insight into the way newly recruited employees enact the process by which their identities are formed and hence act, particularly under conditions of duress or significant organizational disruption in complex organizational settings.

Flying supercapacitors as power smoothing elements in wind generation

This paper presents a capacitor-clamped three-level inverter-based supercapacitor direct integration scheme for wind energy conversion systems. The idea is to increase the capacitance of clamping capacitors with the use of supercapacitors and allow their voltage to vary within a defined range. Even though this unique approach eliminates the need of interfacing dc-dc converters for supercapacitors, the variable voltage operation brings about several challenges. The uneven distribution of space vectors is the major modulation challenge. A space vector modulation method is proposed in this paper to address this issue and to generate undistorted currents even in the presence of dynamic changes in supercapacitor voltages. A supercapacitor voltage equalization algorithm is also presented. Moreover, control strategies of the proposed system are discussed in detail. Simulation and experimental results are presented to verify the efficacy of the proposed system in suppressing short-term wind power fluctuations.