The Rational Design and Evaluation of CK2alpha Mutants Bearing Inhibitor-Refractory Amino Acid Substitutions

CK2 is a ubiquitously expressed and constitutively active serine/threonine protein kinase that is implicated in many cellular functions. Previous studies have indicated that the generation of mutants that are less sensitive to inhibition can be advantageous when studying protein kinases. Importantly, studies have demonstrated that mutants of CK2 rendered less sensitive to inhibition are attainable. To extend these observations, mutants of CK2α were designed and evaluated to test their effect on the inhibition of CK2 by CX-4945 using in vitro enzymatic assays followed by the development of inducible cell lines. CX-4945 is a CK2 inhibitor that has demonstrated anti-tumor activity and has recently been extended into clinical trails phase II. It was demonstrated that a CK2α triple mutant (V66A/H160D/I174A) led to a reduction in the inhibition of CK2 by CX-4945. Generation of CK2 inhibitor-refractory mutants will provide valuable insight regarding the precise functions of CK2 as well as its inhibition

Growing Patronage - Think Tram?

The emerging congestion crisis in Melbourne is underlined by Melbourne City Council’s recent prediction that visitation to the CBD will increase from current levels of around 690,000 people to one million people per day by 2017. Public transport has been identified as one of the keys to solving the demands of travel to and from the city, and to reducing the impact of traffic congestion. This has created a number of challenges for shaping patronage growth on Melbourne’s public transport network, and for making trams a competitive travel option for commuters - especially when a large proportion of the tram network shares road space with other vehicles and is caught in the congestion. The challenge of growing patronage on public transport not only requires incentives for behavioural change amongst commuters, but also for improvements to the level of service offered through tram speeds and frequency, and better access for mobility impaired passengers. This can be achieved through a program of service and infrastructure investments and by appealing to a concern for wider social responsibility (minimising the impact of car pollution, reducing congestion etc). Indeed, if public transport is to successfully address the broader issues of traffic congestion and city pollution, then it must provide the impetus for commuters to rethink their travel behaviours and create a modal shift. This paper will examine Yarra Trams’ approach to growing patronage on a tram system that shares its road space with other vehicles, and also discuss how the Think Tram program provides the foundation and the infrastructure to grow patronage by offering a service that delivers opportunities for a more consistent, accessible and efficient alternative to car travel.Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Every Mother\u27s Prayer

https://digitalcommons.library.umaine.edu/mmb-vp/4869/thumbnail.jp

High-stakes remote-access open-book examinations

The COVID-19 pandemic has led to unprecedented challenges in medical school assessments. Final year high-stakes assessments have classically used closed book examinations (CBEs). Alternative methods of assessment such as open book examinations (OBEs) are emerging but are not routinely used in final year medical school exams. OBEs encourage the use of problem-solving skills more akin to those used in real-life. There is currently limited data comparing OBEs with CBEs. A systematic review showed there was insufficient evidence to support the exclusive use of either CBEs or OBEs in assessment, however the studies conducted to date have rarely looked at high-stakes assessments due to concerns about the validity of OBEs1

Operational modal characterisation for long-term monitoring in offshore structures

In the effort to increase sustainability and help drive the energy sector to support oil and gas decarbonisation, the importance of identifying and characterising the current state of assets is becoming ever more crucial for operators, especially with regards to life extension and repurposing. Structural Health Monitoring (SHM) offers a promising and forward-thinking methodology for tracking asset integrity. In particular, Operational Modal Analysis (OMA) presents a proven, output only method for structure characterisation and modal tracking. However, Environmental and Operational Variations (EOV) can influence the modal properties of the structure making modal parameter estimation and tracking less reliable in the short- and long-term. This study employs an Automated Operational Modal Analysis (AOMA) methodology based on the combination of stochastic subspace identification and natural frequency histogram bin analysis for robust parameter extraction. The methodology is implemented in a complex of three bridge linked offshore platforms. Structural complexity, operational loading and significant modal couplings require sophisticated analysis. The preliminary results show discontinuity of the operational modes over a 6-month long monitoring period. The findings demonstrate the need of further analysis to understand the time-variant parameters which determine structural response across the asset lifetime