The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule

IRE1 couples endoplasmic reticulum unfolded protein load to RNA cleavage events that culminate in the sequence-specific splicing of the Xbp1 mRNA and in the regulated degradation of diverse membrane-bound mRNAs. We report on the identification of a small molecule inhibitor that attains its selectivity by forming an unusually stable Schiff base with lysine 907 in the IRE1 endonuclease domain, explained by solvent inaccessibility of the imine bond in the enzyme-inhibitor complex. The inhibitor (abbreviated 4μ8C) blocks substrate access to the active site of IRE1 and selectively inactivates both Xbp1 splicing and IRE1-mediated mRNA degradation. Surprisingly, inhibition of IRE1 endonuclease activity does not sensitize cells to the consequences of acute endoplasmic reticulum stress, but rather interferes with the expansion of secretory capacity. Thus, the chemical reactivity and sterics of a unique residue in the endonuclease active site of IRE1 can be exploited by selective inhibitors to interfere with protein secretion in pathological settings.

Career development and personal functioning differences between work-bound and non-work bound students

We surveyed 506 Australian high school students on career development (exploration, planning, job-knowledge, decision-making, indecision), personal functioning (well-being, self-esteem, life satisfaction, school satisfaction) and control variables (parents’ education, school achievement), and tested differences among work-bound, college-bound and university-bound students. The work-bound students had the poorest career development and personal functioning, the university-bound students the highest, with the college-bound students falling in-between the other two groups. Work-bound students did poorest, even after controlling for parental education and school achievement. The results suggest a relationship between career development and personal functioning in high school students.

Primary students’ spatial visualization and spatial orientation : an evidence base for instruction

This paper reports on the performance of 58 11 to 12-year-olds on a spatial visualization task and a spatial orientation task. The students completed these tasks and explained their thinking during individual interviews. The qualitative data were analysed to inform pedagogical content knowledge for spatial activities. The study revealed that “matching” or “matching and eliminating” were the typical strategies that students employed on these spatial tasks. However, errors in making associations between parts of the same or different shapes were noted. Students also experienced general difficulties with visual memory and language use to explain their thinking. The students’ specific difficulties in spatial visualization related to obscured items, the perspective used, and the placement and orientation of shapes.

From resource base to dynamic capabilities : an investigation of new firms

Despite the numerous observations that dynamic capabilities lie at the source of competitive advantage, we still have limited knowledge as to how access to firm-based resources and changes to these affect the development of dynamic capabilities. In this paper, we examine founder human capital, access to employee human capital, access to technological expertise, access to other specific expertise, and access to two types of tangible resources in a sample of new firms in Sweden. We empirically measure four dynamic capabilities and find that the nature and effect of resources employed in the development of these capabilities vary greatly. For the most part, there are positive effects stemming from access to particular resources. However, for some resources, such as access to employee human capital and access to financial capital, unexpected negative effects also appear. This study therefore provides statistical evidence as to the varying role of resources in capability development. Importantly, we also find that changes in resource bases have more influential roles in the development of dynamic capabilities than the resource stock variables that were measured at an earlier stage of firm development. This provides empirical support for the notion of treating the firm as a dynamic flow of resources as opposed to a static stock. This finding also highlights the importance of longitudinal designs in studies of dynamic capability development. Further recommendations for future empirical studies of dynamic capabilities are presented.

PhD forum : multiple camera management using wide base-line matching

Manual calibration of large and dynamic networks of cameras is labour intensive and time consuming. This is a strong motivator for the development of automatic calibration methods. Automatic calibration relies on the ability to find correspondences between multiple views of the same scene. If the cameras are sparsely placed, this can be a very difficult task. This PhD project focuses on the further development of uncalibrated wide baseline matching techniques.

The effects of sensing and seizing of market opportunities and reconfiguring activities on the organisational resource base

This study has important implications for marketing theory and practice. In an era of turbulent market environments, the organisational ability to sense and seize market opportunities and to reconfigure the resource base accordingly, has significant effects on performance. This paper uses a dynamic capability framework to explain more explicitly the intricacies of the relationship between sensing and seizing of market opportunities and reconfiguring the resource base (i.e. dynamic capabilities) and the resource base. We investigate how the attributes of dynamic capability deployment, timing, frequency and speed, influence the resource base. We test the proposed framework using survey data from 228 large organisations. Findings show that the timing and frequency of dynamic capability deployment have significant effects on the resource base.

Will they know enough? Pre-service primary teachers' knowledge base for teaching intergrated social sciences

A significant issue in primary teacher education is developing a knowledge base which prepares teachers to teach in a range of subject areas. In Australia, the problem in primary social science education is compounded by the integrated nature of the key learning area of Studies of Society and Environment (SOSE). Recent debates on teaching integrated social sciences omit discussions on the knowledge base for teaching. In this paper, a case study approach is used to investigate primary pre-service teachers’ approaches to developing a knowledge base in designing a SOSE curriculum unit. Data from five teacher-educators who taught primary SOSE curriculum indicates that novice teachers’ subject content knowledge, as revealed through their curriculum planning, lacked a disciplinary basis. However, understanding of inquiry learning, which is fundamental to social science education, was much stronger. This paper identifies a gap in the scholarship on teaching integrated social science and illustrates the need to support and develop primary teachers’ disciplinary knowledge in teacher education.

Alliance supervision to enhance client outcomes

Clinical supervision has traditionally been considered an important part of training and the professional development of therapists, being rated highly in the experience of trainees as well as practitioners in the field (Orlinsky, Botermans, & Ronnestad, 2001; Steven, Goodyear, & Robertson, 1998). However, the evidence base for any supervision approach improving outcomes with clients is lacking (Bambling, & King, 2000). In this chapter an alternate non‐approach bound model of supervision is presented that has preliminary evidence for enhancing client outcomes in brief psychological treatment. The focus of this Three‐Stage Alliance Supervision (TSAS) prioritises the interpersonal process of counselling as an independent factor as well as the core construct through which all technical interventions should be given. Below is a basic introduction to the supervision model used in the first empirical investigation of supervision and client outcome (Bambling, King, Raue, Schweitzer, & Lambert 2006). While this chapter does not constitute the supervision manual it should provide the reader with sufficient knowledge to adopt an alliance focus in their supervision practice.