Chronic myeloid leukemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal

Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is deregulated in CML, with altered expression and response to the BMP ligands shown to impact on LSC expansion and behaviour. In this study, we determined whether alterations in the BMP pathway gene signature had any predictive value for therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2 trial and correlating the data to treatment response using the 18-month follow-up data. There was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response. Therapeutic targeting of CML cells using BMP receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI), indicate a synergistic mode of action. Furthermore, dual treatment resulted in altered cell cycle gene transcription and irreversible cell cycle arrest, along with increased apoptosis compared to single agents. Targeting CML CD34+ cells with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34+ cells and colony formation when compared to normal donor CD34+ cells, both in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC) model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso-endodermal differentiation. These findings indicate that transformed stem cells may be more reliant on BMP signalling than normal stem cells. These changes offer a therapeutic window in CML, with intervention using BMP inhibitors in combination with TKI having the potential to target LSC self-renewal and improve long-term outcome for patients

Diatoms of Northeastern Iowa Fens

Analysis of water samples from 10 fens in NE Iowa, collected 13-14 November 1987, revealed a gradient from acid, low conductivity water conditions (pH 5.6, alkalinity 30 mg/I HCO, conductivity 65 μmho, total hardness 30 mg/I Ca) to circumneutral, moderately conductive conditions (pH 7 .2, alkalinity 390 mg/I, conductivity 705 μmho, total hardness 380 mg/I Ca). Three sites along this gradient were sampled 15 May 1988 and 3 September 1988 to evaluate seasonal variation in water conditions. Examination of composite diatom samples collected concurrently with the water samples yielded 150 taxa, of which 14 are new Iowa distributional records and 6 remain unidentified. Previous investigators have reported 102 of these taxa from other Iowa fens, bogs, or prairie swales. Only 58 have been reported from the Cedar River basin, where most of these fens are located. This evidence suggests these scattered small wetlands resemble similar areas some distance away more than the surrounding surface waters. Distributional patterns of diatoms along the environmental gradient appear sufficiently distinct to permit delineation of species autecology

Supportive leadership and co-worker support for nomophobia reduction: Considering affective commitment and HRM practices

Given the wide range of mobile and communication devices in everyday life and the day-to-day work of most individuals, people often become dependent on their smartphones - this dependency creates a modern phobia. The discomfort or anxiety caused by being unable to use a smartphone is referred to as “Nomophobia.” This paper outlines our approach to survey the impact of supportive leadership and co-worker support on nomophobia, in terms of the role of affective commitment and human resource management (HRM) practices. This study employs structural equation modelling (SEM) based on data obtained from a questionnaire into organizations, with a view to revealing comprehensive findings concerning nomophobia. Additionally, some measures to control nomophobia will be suggested

A prototypical Skin Cancer Information System

Skin cancer is a common problem in Australia and indeed around the world. Within the domain of eHealth, there appears to be no satisfactory clinical software that follows the flow of a normal skin cancer examination. This paper introduces a system that was specifically designed, coded and implemented to store patient health records as a means of registering the diagnoses of skin cancer along with the treatment. The information system was intended to be web-based, and connect to remote database servers. The implemented system was designed to incorporate features such as inserting procedural details, generating forms and reports with interactive interfaces, yet be relatively unsophisticated to use. We expect the system once fully implemented and on line, will aid in Australia’s eHealth industry, delivering more accurate information to doctors and patients in an effort to combat issues involving skin cancer. Other parameters discussed are the need for data encryption of medical records and the role such a system can play in medical information

Innovation through process automation: Factors for success

This paper identifies critical success factors and inhibitors in process improvement initiatives, such as process automation and application integration. Business processes are considered vital organizational assets and key differentiator in a global competitive environment (Seethamraju, 2010). Several business process methodologies were considered to understand the efficacy of process improvement to realise desired benefits. A combined research methodology is used to deep dive into these factors. A pragmatic analysis of the phenomenology of an end-to-end study abroad application process of an Australian university after enabling automation and application integration is presented. In addition, a supplementary analysis of case studies on how different process improvement frameworks influence or inhibit success of process improvement initiatives. Factors in the BPM capability framework were mapped to identify these critical success factors and inhibitors. The outcome of this research will introduce a model to support organisations in continuous improvement initiatives

IT Education vs. Employability Mismatch

We live in a digitized era with rapidly evolving technology; consequently, educational curricula need to be adapted to meet the skills and demands of society. This paper analyses current trends within Australian undergraduate Information Technology (IT) curricula to better understand the education-employability mismatch. Secondary data collection from publicly available unit guides and primary data from interviews with IT employers were gathered to identify the strengths and weaknesses of current IT undergraduate curricula through a matrix. The matrix based on the information literacy framework, coupled with the Australian Qualifications Framework (AQF), will improve the tertiary education curriculum, with a view towards increasing employability rates post-graduation

The Theory and Application of Optical Diagnostic Techniques in the Combustion Chamber of a Diesel Engine

Die Entwicklung moderner Dieselbrennverfahren hinsichtlich minimierter Abgasemissionen und der gleichzeitigen Beibehaltung guter Wirkungsgrade erfordert weitere Kenntnisse über die im Brennraum ablaufenden Prozesse. Gegenstand dieser Arbeit ist die Umsetzung ausgewählter optischer Messtechniken in einem neuen, optisch zugänglichen Heavy Duty Dieselmotor und die Analyse der am Prüfstand gewonnenen Ergebnisse vor dem Hintergrund des heutigen Wissenstands

Australian Undergraduate IT Curricula: Employer Perspectives

This research paper outlines our research approach relating to analysing current trends within Australian undergraduate BIT curricula. With a variety of data collection techniques, we seek to address a knowledge gap in the literature through identifying the strengths and challenges facing university curricula. Closing the education-employment gap requires the involvement of all stakeholder groups (academics, employers, and students) (Trauth et al, 1993). We develop an educational matrix based on the information literacy framework and the Australian Qualifications Framework (AQF). Secondary data collection is conducted from a range of NSW BIT core units to map against this framework, as well as conducting pilot interviews with selected employers to gain a better understanding of the current curriculum and the needs of the employers. The outcome of this research will enable current educational sectors to improve the tertiary education curriculum, with a view towards increasing employability rates post-graduation, which may be generalizable to other nations