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.

Super-resolved faces for improved face recognition from surveillance video advances in biometrics

Characteristics of surveillance video generally include low resolution and poor quality due to environmental, storage and processing limitations. It is extremely difficult for computers and human operators to identify individuals from these videos. To overcome this problem, super-resolution can be used in conjunction with an automated face recognition system to enhance the spatial resolution of video frames containing the subject and narrow down the number of manual verifications performed by the human operator by presenting a list of most likely candidates from the database. As the super-resolution reconstruction process is ill-posed, visual artifacts are often generated as a result. These artifacts can be visually distracting to humans and/or affect machine recognition algorithms. While it is intuitive that higher resolution should lead to improved recognition accuracy, the effects of super-resolution and such artifacts on face recognition performance have not been systematically studied. This paper aims to address this gap while illustrating that super-resolution allows more accurate identification of individuals from low-resolution surveillance footage. The proposed optical flow-based super-resolution method is benchmarked against Baker et al.’s hallucination and Schultz et al.’s super-resolution techniques on images from the Terrascope and XM2VTS databases. Ground truth and interpolated images were also tested to provide a baseline for comparison. Results show that a suitable super-resolution system can improve the discriminability of surveillance video and enhance face recognition accuracy. The experiments also show that Schultz et al.’s method fails when dealing surveillance footage due to its assumption of rigid objects in the scene. The hallucination and optical flow-based methods performed comparably, with the optical flow-based method producing less visually distracting artifacts that interfered with human recognition.

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.

A Taxonomy for Homework Used by Mental Health Case Managers When Working with Individuals Diagnosed with Severe Mental Illness

A survey was completed by 122 case managers describing the types of homework assignments commonly used with individuals diagnosed with severe mental illness (SMI). Homework types were categorized using a 12-item homework description taxonomy and in relation to the 22 domains of the Camberwell Assessment of Need (CAN). Case managers predominately reported using behaviourally based homework tasks such as scheduling activities and the development of personal hygiene skills. Homework focused on CAN areas of need in relation to Company, Psychological Distress, Psychotic Symptoms and Daytime Activities. The applications of the taxonomy for both researchers and case managers are discussed.

Re-conceptualising and re-positioning Australian library and information science education for the 21st century [Final Report 2011]

How can Australian library and information science (LIS) education produce, in a sustainable manner, the diverse supply of graduates with the appropriate attributes to develop and maintain high quality professional practice in the rapidly changing 21st century? This report presents the key findings of a project that has examined this question through research into future directions for LIS education in Australia. Titled Re-conceptualising and re-positioning Australian library and information science education for the twenty-first century, the purpose of the project was to establish a consolidated and holistic picture of the Australian LIS profession, and identify how its future education and training can be mediated in a cohesive and sustainable manner. The project was undertaken with a team of 12 university and vocational LIS educators from 11 institutions around Australia between November 2009 and December 2010. Collectively, these eleven institutions represented the broad spectrum and diversity of LIS education in Australia, and enabled the project to examine education for the information profession in a holistic and synergistic manner. Participating institutions in the project included Queensland University of Technology (Project Leader), Charles Sturt University, Curtin University of Technology, Edith Cowan University, Monash University, RMIT University, University of Canberra, University of South Australia, University of Tasmania, University of Technology Sydney and Victoria University. The inception and need for the project was motivated by a range of factors. From a broad perspective several of these factors relate to concerns raised at national and international levels regarding problems with education for LIS. In addition, the motivation and need for the project also related to some unique challenges that LIS education faces in the Australian tertiary education landscape. Over recent years a range of responses to explore the various issues confronting LIS education in Australia have emerged at local and national levels however this project represented the first significant investment of funding for national research in this area. In this way, the inception of the project offered a unique opportunity and powerful mechanism through which to bring together key stakeholders and inspire discourse concerning future education for the profession. Therefore as the first national project of its kind, its intent has been to provide foundation research that will inform and guide future directions for LIS education and training in Australia. The primary objective of the project was to develop a Framework for the Education of the Information Professions in Australia. The purpose of this framework was to provide evidence based strategic recommendations that would guide Australia’s future education for the information professions. Recognising the three major and equal players in the education process the project was framed around three areas of consideration: LIS students, the LIS workforce and LIS educators. Each area of consideration aligned to a research substudy in the project. The three research substudies were titled Student Considerations, Workforce Planning Considerations and Tertiary Education Considerations. The Students substudy provided a profile of LIS students and an analysis of their choices, experiences and expectations in regard to LIS education and their graduate destinations. The Workforce substudy provided an overview and analysis of the nature of the current LIS workforce, including a focus on employer expectations and employment opportunities and comment on the core and elective skill, knowledge and attitudes of current and future LIS professionals. Finally the Tertiary Education substudy provided a profile of LIS educators and an analysis of their characteristics and experiences including the key issues and challenges. In addition it also explored current national and international trends and priorities impacting on LIS education. The project utilised a Community Based Participatory Research (CBPR) approach. This approach involves all members of the community in all aspects of the project. It recognised the unique strengths and perspectives that community members bring to the process. For this project ‘community’ comprised of all individuals who have a role in, or a vested interest in, LIS education and included LIS educators, professionals, employers, students and professional associations. Individuals from these sub-groups were invited to participate in a range of aspects of the project from design through to implementation and evaluation. A range of research methodologies were used to consider the many different perspectives of LIS education, including employers and recruiters, professional associations, students, graduates and LIS teaching staff. Data collection involved a mixed method approach of questionnaires, focus groups, semi-structured interviews and environmental scans. An array of approaches was selected to ensure that broadest possible access to different facets of the information profession would be achieved. The main findings and observations from each substudy have highlighted a range of challenges for LIS education that need to be addressed. These findings and observations have grounded the development of the Framework for the Education of the Information Professions in Australia. The framework presents eleven recommendations to progress the national approach to LIS education and guide Australia’s future education for the information professions. The framework will be used by the LIS profession, most notably its educators, as strategic directions for the future of LIS education in Australia. Framework for the Education of the Information Professions in Australia: Recommendation 1: It is recommended that a broader and more inclusive vocabulary be adopted that both recognises and celebrates the expanding landscape of the field, for example ‘information profession’, ‘information sector’, ‘information discipline’ and ‘information education’. Recommendation 2: It is recommended that a self-directed body composed of information educators be established to promote, support and lead excellence in teaching and research within the information discipline. Recommendation 3: It is recommended that Australia’s information discipline continue to develop excellence in information research that will raise the discipline’s profile and contribute to its prominence within the national and international arena. Recommendation 4: It is recommended that further research examining the nature and context of Australia’s information education programs be undertaken to ensure a sustainable and relevant future for the discipline. Recommendation 5: It is recommended that further research examining the pathways and qualifications available for entry into the Australian information sector be undertaken to ensure relevance, attractiveness, accessibility and transparency. Recommendation 6: It is recommended that strategies are developed and implemented to ensure the sustainability of the workforce of information educators. Recommendation 7: It is recommended that a national approach to promoting and marketing the information profession and thereby attracting more students to the field is developed. Recommendation 8: It is recommended that Australia’s information discipline continues to support a culture of quality teaching and learning, especially given the need to accommodate a focus on the broader information landscape and more flexible delivery options. Recommendation 9: It is recommended that strategies are developed that will support and encourage collaboration between information education within the higher education and VET sectors. Recommendation 10: It is recommended that strategies and forums are developed that will support the information sector working together to conceptualise and articulate their professional identity and educational needs. Recommendation 11: It is recommended that a research agenda be established that will identify and prioritise areas in which further development or work is needed to continue advancing information education in Australia. The key findings from this project confirm that a number of pressing issues are confronting LIS education in Australia. Left unaddressed these issues will have significant implications for the future of LIS education as well as the broader LIS profession. Consequently creating a sustainable and cohesive future can only be realised through cooperation and collaboration among all stakeholders including those with the capacity to enact radical change in university and vocational institutions. Indeed the impending adoption and implementation of the project’s recommendations will fundamentally determine whether Australian LIS education is assured both for the present day and into the future.

Turbulent measurements in a small subtropical estuary with semidiurnal tides

Since predictions of scalar dispersion in small estuaries can rarely be predicted accurately, new field measurements were conducted continuously at relatively high frequency for up to 50 h (per investigation) in a small subtropical estuary with semidiurnal tides. The bulk flow parameters varied in time with periods comparable to tidal cycles and other large-scale processes. The turbulence properties depended upon the instantaneous local flow properties. They were little affected by the flow history, but their structure and temporal variability were influenced by a variety of parameters including the tidal conditions and bathymetry. A striking feature of the data sets was the large fluctuations in all turbulence characteristics during the tidal cycle, and basic differences between neap and spring tide turbulence.

Process mining manifesto

Process mining techniques are able to extract knowledge from event logs commonly available in today’s information systems. These techniques provide new means to discover, monitor, and improve processes in a variety of application domains. There are two main drivers for the growing interest in process mining. On the one hand, more and more events are being recorded, thus, providing detailed information about the history of processes. On the other hand, there is a need to improve and support business processes in competitive and rapidly changing environments. This manifesto is created by the IEEE Task Force on Process Mining and aims to promote the topic of process mining. Moreover, by defining a set of guiding principles and listing important challenges, this manifesto hopes to serve as a guide for software developers, scientists, consultants, business managers, and end-users. The goal is to increase the maturity of process mining as a new tool to improve the (re)design, control, and support of operational business processes.

Mixed convection laminar flow along a horizontal plate subject to streamwise sinusoidal surface temperature

Mixed convection of a two-dimensional laminar incompressible flow along a horizontal flat plate with streamwise sinusoidal surface temperature has been numerically investigated for different values of Rayleigh number and Reynolds number for constant values of Prandtl number, amplitude and frequency of periodic temperature. The numerical scheme is based on the finite element method adapted to rectangular non-uniform mesh elements by a non-linear parametric solution algorithm. The fluid considered in this study is air. The results are obtained for the Rayleigh number and Reynolds number ranging from 102 to 104 and 1 to 100, respectively, with constant physical properties for the fluid medium considered. Velocity and temperature profiles, streamlines, isotherms, and average Nusselt numbers are presented to observe the effect of the investigating parameters on fluid flow and heat transfer characteristics. The present results show that the convective phenomena are greatly influenced by the variation of Rayleigh numbers and Reynolds number.