Nitrogen and phosphorus transformations in fixed-film biofilters subjected to aeration/no-aeration cycles

Despite recent developments in fixed-film combined biological nutrients removal (BNR) technology; fixed-film systems (i.e., biofilters), are still at the early stages of development and their application has been limited to a few laboratory-scale experiments. Achieving enhanced biological phosphorus removal in fixed-film systems requires exposing the micro-organisms and the waste stream to alternating anaerobic/aerobic or anaerobic/anoxic conditions in cycles. The concept of cycle duration (CD) as a process control parameter is unique to fixed-film BNR systems, has not been previously investigated, and can be used to optimise the performance of such systems. The CD refers to the elapsed time before the biomass is re-exposed to the same environmental conditions in cycles. Fixed-film systems offer many advantages over suspended growth systems such as reduced operating costs, simplicity of operation, absence of sludge recycling problems, and compactness. The control of nutrient discharges to water bodies, improves water quality, fish production, and allow water reuse. The main objective of this study was to develop a fundamental understanding of the effect of CD on the transformations of nutrients in fixed-film biofilter systems subjected to alternating aeration I no-aeration cycles A fixed-film biofilter system consisting of three up-flow biofilters connected in series was developed and tested. The first and third biofilters were operated in a cyclic mode in which the biomass was subjected to aeration/no-aeration cycles. The influent wastewater was simulated aquaculture whose composition was based on actual water quality parameters of aquacuture wastewater from a prawn grow-out facility. The influent contained 8.5 - 9:3 mg!L a111monia-N, 8.5- 8.7 mg/L phosphate-P, and 45- 50 mg!L acetate. Two independent studies were conducted at two biofiltration rates to evaluate and confirm the effect of CD on nutrient transformations in the biofilter system for application in aquaculture: A third study was conducted to enhance denitrification in the system using an external carbon- source at a rate varying from 0-24 ml/min. The CD was varied in the range of0.25- 120 hours for the first two studies and fixed at 12 hours for the third study. This study identified the CD as an important process control parameter that can be used to optimise the performance of full-scale fixed-film systems for BNR which represents a novel contribution in this field of research. The CD resulted in environmental conditions that inhibited or enhanced nutrient transformations. The effect of CD on BNR in fixed-film systems in terms of phosphorus biomass saturation and depletion has been established. Short CDs did not permit the establishment of anaerobic activity in the un-aerated biofilter and, thus, inhibited phosphorus release. Long CDs resulted in extended anaerobic activity and, thus, resulted in active phosphorus release. Long CDs, however, resulted in depleting the biomass phosphorus reservoir in the releasing biofilter and saturating the biomass phosphorus reservoir in the up-taking biofilter in the cycle. This phosphorus biomass saturation/depletion phenomenon imposes a practical limit on how short or long the CD can be. The length of the CD should be somewhere just before saturation or depletion occur and for the system tested, the optimal CD was 12 hours for the biofiltration rates tested. The system achieved limited net phosphorus removal due to the limited sludge wasting and lack of external carbon supply during phosphorus uptake. The phosphorus saturation and depletion reflected the need to extract phosphorus from the phosphorus-rich micro-organisms, for example, through back-washing. The major challenges of achieving phosphorus removal in the system included: (I) overcoming the deterioration in the performance of the system during the transition period following the start of each new cycle; and (2) wasting excess phosphorus-saturated biomass following the aeration cycle. Denitrification occurred in poorly aerated sections of the third biofilter and generally declined as the CD increased and as the time progressed in the individual cycle. Denitrification and phosphorus uptake were supplied by an internal organic carbon source, and the addition of an external carbon source (acetate) to the third biofilter resulted in improved denitrification efficiency in the system from 18.4 without supplemental carbon to 88.7% when the carbon dose reached 24 mL/min The removal of TOC and nitrification improved as the CD increased, as a result of the reduction in the frequency of transition periods between the cycles. A conceptual design of an effective fixed-film BNR biofilter system for the treatment of the influent simulated aquaculture wastewater was proposed based on the findings of the study.

Generalised self-efficacy in relation to the life transitions of adult learners in a university setting : towards a narrative constructivist model of self-regulation

This paper demonstrates a model of self-regulation based on a qualitative research project with adult learners undertaking an undergraduate degree. The narrative about the participant’s life transitions, co-constructed with the researcher, yielded data about their generalised self-efficacy and resulted in a unique self-efficacy narrative for each participant. A model of self-regulation is proposed with potential applications for coaching, counselling and psychotherapy. A narrative method was employed to construct narratives about an individual’s self-efficacy in relation to their experience of learning and life transitions. The method involved a cyclical and iterative process using qualitative interviews to collect life history data from participants. In addition, research participants completed reflective homework tasks, and this data was included in the participant’s narratives. A highly collaborative method entailed narratives being co-constructed by researcher and research participants as the participants were guided in reflecting on their experience in relation to learning and life transitions; the reflection focused on behaviour, cognitions and emotions that constitute a sense of self-efficacy. The analytic process used was narrative analysis, in which life is viewed as constructed and experienced through the telling and retelling of stories and hence the analysis is the creation of a coherent and resonant story. The method of constructing self-efficacy narratives was applied to a sample of mature aged students starting an undergraduate degree. The research outcomes confirmed a three-factor model of self-efficacy, comprising three interrelated stages: initiating action, applying effort, and persistence in overcoming difficulties. Evaluation of the research process by participants suggested that they had gained an enhanced understanding of self-efficacy from their participation in the research process, and would be able to apply this understanding to their studies and other endeavours in the future. A model of self-regulation is proposed as a means for coaches, counsellors and psychotherapists working from a narrative constructivist perspective to assist clients facing life transitions by helping them generate selfefficacious cognitions, emotions and behaviour.

Towards a method of constructing self-efficacy narratives.

This paper outlines a method of constructing narratives about an individual’s self-efficacy. Self-efficacy is defined as “people’s judgments of their capabilities to organise and execute courses of action required to attain designated types of performances” (Bandura, 1986, p. 391), and as such represents a useful construct for thinking about personal agency. Social cognitive theory provides the theoretical framework for understanding the sources of self-efficacy, that is, the elements that contribute to a sense of self-efficacy. The narrative approach adopted offers an alternative to traditional, positivist psychology, characterised by a preoccupation with measuring psychological constructs (like self-efficacy) by means of questionnaires and scales. It is argued that these instruments yield scores which are somewhat removed from the lived experience of the person—respondent or subject—associated with the score. The method involves a cyclical and iterative process using qualitative interviews to collect data from participants – four mature aged university students. The method builds on a three-interview procedure designed for life history research (Dolbeare & Schuman, cited in Seidman, 1998). This is achieved by introducing reflective homework tasks, as well as written data generated by research participants, as they are guided in reflecting on those experiences (including behaviours, cognitions and emotions) that constitute a sense of self-efficacy, in narrative and by narrative. The method illustrates how narrative analysis is used “to produce stories as the outcome of the research” (Polkinghorne, 1995, p.15), with detail and depth contributing to an appreciation of the ‘lived experience’ of the participants. The method is highly collaborative, with narratives co-constructed by researcher and research participants. The research outcomes suggest an enhanced understanding of self-efficacy contributes to motivation, application of effort and persistence in overcoming difficulties. The paper concludes with an evaluation of the research process by the students who participated in the author’s doctoral study.

Sustainable urban development : formulation of indicator-based residential sustainability assessment framework for local level

Purpose–The purpose of this paper is to formulate a conceptual framework for urban sustainability indicators selection. This framework will be used to develop an indicator-based evaluation method for assessing the sustainability levels of residential neighbourhood developments in Malaysia. Design/methodology/approach–We provide a brief overview of existing evaluation frameworks for sustainable development assessment. We then develop a conceptual Sustainable Residential Neighbourhood Assessment (SNA) framework utilising a four-pillar sustainability framework (environmental, social, economic and institutional) and a combination of domain-based and goal-based general frameworks. This merger offers the advantages of both individual frameworks, while also overcoming some of their weaknesses when used to develop the urban sustainability evaluation method for assessing residential neighbourhoods. Originality/value–This approach puts in evidence that many of the existing frameworks for evaluating urban sustainability do not extend their frameworks to include assessing housing sustainability at a local level. Practical implications–It is expected that the use of the indicator-based Sustainable Neighbourhood Assessment framework will present a potential mechanism for planners and developers to evaluate and monitor the sustainability performance of residential neighbourhood developments.

Dynamics of pattern writing and erasure in photorefractive lithium niobate for data storage applications

The present rate of technological advance continues to place significant demands on data storage devices. The sheer amount of digital data being generated each year along with consumer expectations, fuels these demands. At present, most digital data is stored magnetically, in the form of hard disk drives or on magnetic tape. The increase in areal density (AD) of magnetic hard disk drives over the past 50 years has been of the order of 100 million times, and current devices are storing data at ADs of the order of hundreds of gigabits per square inch. However, it has been known for some time that the progress in this form of data storage is approaching fundamental limits. The main limitation relates to the lower size limit that an individual bit can have for stable storage. Various techniques for overcoming these fundamental limits are currently the focus of considerable research effort. Most attempt to improve current data storage methods, or modify these slightly for higher density storage. Alternatively, three dimensional optical data storage is a promising field for the information storage needs of the future, offering very high density, high speed memory. There are two ways in which data may be recorded in a three dimensional optical medium; either bit-by-bit (similar in principle to an optical disc medium such as CD or DVD) or by using pages of bit data. Bit-by-bit techniques for three dimensional storage offer high density but are inherently slow due to the serial nature of data access. Page-based techniques, where a two-dimensional page of data bits is written in one write operation, can offer significantly higher data rates, due to their parallel nature. Holographic Data Storage (HDS) is one such page-oriented optical memory technique. This field of research has been active for several decades, but with few commercial products presently available. Another page-oriented optical memory technique involves recording pages of data as phase masks in a photorefractive medium. A photorefractive material is one by which the refractive index can be modified by light of the appropriate wavelength and intensity, and this property can be used to store information in these materials. In phase mask storage, two dimensional pages of data are recorded into a photorefractive crystal, as refractive index changes in the medium. A low-intensity readout beam propagating through the medium will have its intensity profile modified by these refractive index changes and a CCD camera can be used to monitor the readout beam, and thus read the stored data. The main aim of this research was to investigate data storage using phase masks in the photorefractive crystal, lithium niobate (LiNbO3). Firstly the experimental methods for storing the two dimensional pages of data (a set of vertical stripes of varying lengths) in the medium are presented. The laser beam used for writing, whose intensity profile is modified by an amplitudemask which contains a pattern of the information to be stored, illuminates the lithium niobate crystal and the photorefractive effect causes the patterns to be stored as refractive index changes in the medium. These patterns are read out non-destructively using a low intensity probe beam and a CCD camera. A common complication of information storage in photorefractive crystals is the issue of destructive readout. This is a problem particularly for holographic data storage, where the readout beam should be at the same wavelength as the beam used for writing. Since the charge carriers in the medium are still sensitive to the read light field, the readout beam erases the stored information. A method to avoid this is by using thermal fixing. Here the photorefractive medium is heated to temperatures above 150�C; this process forms an ionic grating in the medium. This ionic grating is insensitive to the readout beam and therefore the information is not erased during readout. A non-contact method for determining temperature change in a lithium niobate crystal is presented in this thesis. The temperature-dependent birefringent properties of the medium cause intensity oscillations to be observed for a beam propagating through the medium during a change in temperature. It is shown that each oscillation corresponds to a particular temperature change, and by counting the number of oscillations observed, the temperature change of the medium can be deduced. The presented technique for measuring temperature change could easily be applied to a situation where thermal fixing of data in a photorefractive medium is required. Furthermore, by using an expanded beam and monitoring the intensity oscillations over a wide region, it is shown that the temperature in various locations of the crystal can be monitored simultaneously. This technique could be used to deduce temperature gradients in the medium. It is shown that the three dimensional nature of the recording medium causes interesting degradation effects to occur when the patterns are written for a longer-than-optimal time. This degradation results in the splitting of the vertical stripes in the data pattern, and for long writing exposure times this process can result in the complete deterioration of the information in the medium. It is shown in that simply by using incoherent illumination, the original pattern can be recovered from the degraded state. The reason for the recovery is that the refractive index changes causing the degradation are of a smaller magnitude since they are induced by the write field components scattered from the written structures. During incoherent erasure, the lower magnitude refractive index changes are neutralised first, allowing the original pattern to be recovered. The degradation process is shown to be reversed during the recovery process, and a simple relationship is found relating the time at which particular features appear during degradation and recovery. A further outcome of this work is that the minimum stripe width of 30 ìm is required for accurate storage and recovery of the information in the medium, any size smaller than this results in incomplete recovery. The degradation and recovery process could be applied to an application in image scrambling or cryptography for optical information storage. A two dimensional numerical model based on the finite-difference beam propagation method (FD-BPM) is presented and used to gain insight into the pattern storage process. The model shows that the degradation of the patterns is due to the complicated path taken by the write beam as it propagates through the crystal, and in particular the scattering of this beam from the induced refractive index structures in the medium. The model indicates that the highest quality pattern storage would be achieved with a thin 0.5 mm medium; however this type of medium would also remove the degradation property of the patterns and the subsequent recovery process. To overcome the simplistic treatment of the refractive index change in the FD-BPM model, a fully three dimensional photorefractive model developed by Devaux is presented. This model shows significant insight into the pattern storage, particularly for the degradation and recovery process, and confirms the theory that the recovery of the degraded patterns is possible since the refractive index changes responsible for the degradation are of a smaller magnitude. Finally, detailed analysis of the pattern formation and degradation dynamics for periodic patterns of various periodicities is presented. It is shown that stripe widths in the write beam of greater than 150 ìm result in the formation of different types of refractive index changes, compared with the stripes of smaller widths. As a result, it is shown that the pattern storage method discussed in this thesis has an upper feature size limit of 150 ìm, for accurate and reliable pattern storage.

Longitudinal evaluations of student satisfaction with a postgraduate unit using importance-performance analysis

The Australian tourism tertiary education sector operates in a competitive and dynamic environment, which necessitates a market orientation to be successful. Academic staff and management in the sector must regularly assess the perceptions of prospective and current students and monitor the satisfaction levels of current students. This study is concerned with the setting and monitoring of satisfaction levels of current students, reporting the results of three longitudinal investigations of student satisfaction in a postgraduate unit. The study also addresses a limitation of a university’s generic teaching evaluation instrument. Importance-Performance Analysis (IPA) has been recommended as a simple but effective tool for overcoming the deficiencies of many student evaluation studies, which have generally measured only attribute performance at the end of a semester. IPA was used to compare student expectations of the unit at the beginning of a semester with their perceptions of performance 10 weeks later. The first stage documented key benchmarks for which amendments to the unit based on student feedback could be evaluated during subsequent teaching periods.

‘You’re a bad driver but I just made a mistake’ : attribution differences between the ‘victims’ and ‘perpetrators’ of scenario-based aggressive driving incidents

Driver aggression is an increasing concern for motorists, with some research suggesting that drivers who behave aggressively perceive their actions as justified by the poor driving of others. Thus attributions may play an important role in understanding driver aggression. A convenience sample of 193 drivers (aged 17-36) randomly assigned to two separate roles (‘perpetrators’ and ‘victims’) responded to eight scenarios of driver aggression. Drivers also completed the Aggression Questionnaire and Driving Anger Scale. Consistent with the actor-observer bias, ‘victims’ (or recipients) in this study were significantly more likely than ‘perpetrators’ (or instigators) to endorse inadequacies in the instigator’s driving skills as the cause of driver aggression. Instigators were significantly more likely attribute the depicted behaviours to external but temporary causes (lapses in judgement or errors) rather than stable causes. This suggests that instigators recognised drivers as responsible for driving aggressively but downplayed this somewhat in comparison to ‘victims’/recipients. Recipients and instigators agreed that the behaviours were examples of aggressive driving but instigators appeared to focus on the degree of intentionality of the driver in making their assessments while recipients appeared to focus on the safety implications. Contrary to expectations, instigators gave mean ratings of the emotional impact of driving aggression on recipients that were higher in all cases than the mean ratings given by the recipients. Drivers appear to perceive aggressive behaviours as modifiable, with the implication that interventions could appeal to drivers’ sense of self-efficacy to suggest strategies for overcoming plausible and modifiable attributions (e.g. lapses in judgement; errors) underpinning behaviours perceived as aggressive.

Preface : rethinking sustainable development : urban management, engineering, and design

In an atmosphere where civilization is progressing and becoming more aware of the consequences of careless development decisions, rethinking sustainable development - particularly sustainable urban and infrastructure development - has become an inevitable necessity. ------ ----- Rethinking Sustainable Development: Urban Management, Engineering, and Design considers the role of urban, regional and infrastructure planning in achieving sustainable urban and infrastructure development, providing insights into overcoming the consequences of unsustainable development. This companion volume to Sustainable Urban and Regional Infrastructure: Technology, Planning and Management, overviews all aspects of sustainable urban and infrastructure development.

Preface

In an atmosphere where civilization is progressing and becoming more aware of the consequences of careless development decisions, rethinking sustainable development–particularly sustainable urban and infrastructure development–has become an inevitable necessity. Rethinking Sustainable Development: Urban Management, Engineering, and Design considers the role of urban, regional and infrastructure planning in achieving sustainable urban and infrastructure development, providing insights into overcoming the consequences of unsustainable development. This companion volume to Sustainable Urban and Regional Infrastructure: Technology, Planning and Management, overviews all aspects of sustainable urban and infrastructure development.

The identification of Malaysian contractor satisfaction dimensions : a strategy for continuous improvement

The unique characteristics of the construction industry - such as the fragmentation of its processes, varied scope of works and diversity of its participants - are contributory factors to poor project performance. Several issues are unresolved due to the lack of a comprehensive technique to measure project outcomes including: inefficient decision making, insufficient communication, uncertain site conditions, a continuously changing environment, inharmonious working relationships, mismatched objectives within the project team and a blame culture. One approach to overcoming these problems appears to be to measure performance by gauging contractor satisfaction (Co-S) levels, but this has not been widely investigated as yet. Additionally, the key Co-S dimensions at the project level are still not fully identified. ----- ----- This paper concerns a study of satisfaction dimensions, primarily by a postal questionnaire survey of construction contractors registered by the Malaysian Construction Industry Development Board (CIDB). Eight satisfaction dimensions are identified that are significantly and substantially relate to these contractors - comprising: project cost performance, schedule performance, product performance, design satisfaction, site safety, project profitability, business performance and relationships between participants. -Each of these dimensions is accorded different priority levels of satisfaction by different contractors. ----- ----- The output of this study will be useful in raising the awareness and understanding of project teams regarding contractors’ needs, mutual objectives and open communication to help to deliver a successful project.

Mooting and technology : to what extent does using technology improve the mooting experience for students?

It is generally acknowledged that mooting is an effective way to enhance the teaching of practical skills in legal education as well as to provide an authentic learning experience with links to the real world. However, there are a number of impediments to students participating in mooting; in particular being located off-campus, inexperience and lack of time. It has been suggested that technology may be a means of overcoming these impediments. However the use of technology in mooting has not been tested. This paper will report on a trial of the use of Second Life and Elluminate and videoconferencing as platforms for the conduct of moots. The trials identified limitations in the use of technology for mooting in particularly in relation to the development of advocacy skills. The paper will conclude that these limitations can be overcome by careful consideration of the appropriate technology to be used depending on the context and the objectives to be achieved by the moot. It will also suggest that in order to provide an authentic use of online communication technology in a court setting, the best available technology should be used for the conduct of moot competitions.

Building support for learning within a Doctor of Education programme

Professional doctorates were introduced in the 1990s for practitioners to research ‘real-world’ problems relevant to their respective workplace communities and contexts. An array of difficulties faces professional doctoral students as they transition from professionals to practitioner researchers. This study sought to understand the learning journey of a cohort of students at an Australian university and to assess whether the cohort approach provided the necessary support for students to reach their scholarly destinations. Throughout the first 18 months of the programme, focus group interviews and surveys were conducted to gauge students’ experiences and to evaluate developments for support within the programme. Utilising a socio-cultural perspective helped identify and explain the importance of shared practice in fostering learning, the development of academic and researcher identities, and the role of communities of practice. Challenges of managing time and overcoming the professional and academe divide were facilitated by the evolving developments of the programme.

Photocatalytic hydrogen production with iron oxide under solar irradiation

As solar hydrogen is a sustainable and environmental friendly energy carrier, it is considered to take the place of fossil fuels in the near future. Solar hydrogen can be generated by splitting of water under solar light illumination. In this study, the use of nanostructured hematite thin-film electrodes in photocatalytic water splitting was investigated. Hematite (á-Fe2O3) has a narrow band-gap of 2.2 eV, which is able to utilise approximately 40% of solar radiation. However, poor photoelectrochemical performance is observed for hematite due to low electrical conductivity and a high rate of electron-hole recombination. An extensive review of useful measures taken to overcoming the disadvantages of hematite so as to enhance its performance was presented including thin-film structure, nanostructuring, doping, etc. Since semiconductoring materials which exhibit an inverse opal structure are expected to have a high surface-volume ratio, unique optical characteristics and a shorter distance for photogenerated holes to travel to the electrode/electrolyte interface, inverse opals of hematite thin films deposited on FTO glass substrate were successfully prepared by doctor blading using PMMA as a template. However, due to the poor adhesion of the films, an acidic medium (i.e., 2 M HCl) was employed to significantly enhance the adhesion of the films, which completely destroyed the inverse opal structure. Therefore, undoped, Ti and Zn-doped hematite thin films deposied on FTO glass substrate without an inverse opal structure were prepared by doctor blading and spray pyrolysis and characterised using SEM, EDX, XRD, TGA, UV-Vis spectroscopy and photoelectrochemical measurements. Regarding the doped hematite thin films prepared by doctor blading, the photoelectrochemical activity of the hematite photoelectrodes was improved by incorporation of Ti, most likely owing to the increased electrical conductivity of the films, the stabilisation of oxygen vacancies by Ti4+ ions and the increased electric field of the space charge layer. A highest photoresponse was recorded in case of 2.5 at.% Ti which seemed to be an optimal concentration. The effect of doping content, thickness, and calcination temperature on the performance of the Ti-doped photoelectrodes was investigated. Also, the photoactivity of the 2.5 at.% Ti-doped samples was examined in two different types of electrochemical cells. Zn doping did not enhance the photoactivity of the hematite thin films though Zn seemed to enhance the hole transport due to the slow hole mobility of hematite which could not be overcome by the enhancement. The poor performance was also obtained for the Ti-doped samples prepared by spray pyrolysis, which appeared to be a result of introduction of impurities from the metallic parts of the spray gun in an acidic medium. Further characterisation of the thin-film electrodes is required to explain the mechanism by which enhanced performance was obtained for Ti-doped electrodes (doctor blading) and poor photoactivity for Zn and Ti-doped samples which were synthesised by doctor blading and spray pyrolysis, respectively. Ti-doped hematite thin films will be synthesised in another way, such as dip coating so as to maintain an inverse opal structure as well as well adhesion. Also, a comparative study of the films will be carried out.

Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells

Patients with metastatic melanoma or multiple myeloma have a dismal prognosis because these aggressive malignancies resist conventional treatment. A promising new oncologic approach uses molecularly targeted therapeutics that overcomes apoptotic resistance and, at the same time, achieves tumor selectivity. The unexpected selectivity of proteasome inhibition for inducing apoptosis in cancer cells, but not in normal cells, prompted us to define the mechanism of action for this class of drugs, including Food and Drug Administration-approved bortezomib. In this report, five melanoma cell lines and a myeloma cell line are treated with three different proteasome inhibitors (MG-132, lactacystin, and bortezomib), and the mechanism underlying the apoptotic pathway is defined. Following exposure to proteasome inhibitors, effective killing of human melanoma and myeloma cells, but not of normal proliferating melanocytes, was shown to involve p53-independent induction of the BH3-only protein NOXA. Induction of NOXA at the protein level was preceded by enhanced transcription of NOXA mRNA. Engagement of mitochondrial-based apoptotic pathway involved release of cytochrome c, second mitochondria-derived activator of caspases, and apoptosis-inducing factor, accompanied by a proteolytic cascade with processing of caspases 9, 3, and 8 and poly(ADP)-ribose polymerase. Blocking NOXA induction using an antisense (but not control) oligonucleotide reduced the apoptotic response by 30% to 50%, indicating a NOXA-dependent component in the overall killing of melanoma cells. These results provide a novel mechanism for overcoming the apoptotic resistance of tumor cells, and validate agents triggering NOXA induction as potential selective cancer therapeutics for life-threatening malignancies such as melanoma and multiple myeloma.

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.