Monte Carlo Analysis of Neck Linker Extension in Kinesin Molecular Motors

Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step – diffusion of the tethered head to the next binding site – is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring), Increasing Stiffness (analogous to a Worm-Like Chain), and Reflecting (negligible stiffness up to a limiting contour length). Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant containing an extended neck linker domain. When tethered by an increasingly stiff spring, the head is predicted to spend an unrealistically short amount of time within the binding zone, and extending the neck is predicted to increase both the velocity and processivity, contrary to experiments. These results suggest that the Worm-Like Chain is not an adequate model for the flexible neck linker domain. The model can be reconciled with experimental data if the neck linker is either much more compliant or much stiffer than generally assumed, or if weak kinesin-microtubule interactions stabilize the diffusing head near its binding site

Recognising refugees' non-formally and informally acquired vocational skills for use in Germany’s labour market

The influx of asylum seekers into the European Union (EU) in 2015-2016 has turned the recognition of non-formal and informal learning (NFIL) into an integration priority and challenge. In EU terminology this process is called ‘validation’. Already in 2012, the Council of the EU had urged member states to create mechanisms for the validation of NFIL by no later than 2018. However, the issue has remained systematically addressed by few. Moreover, across all countries, disadvantaged groups such as refugees still benefit least from validation. Yet little is known about the reasons for this – a question to which this study aims to contribute understanding. Notably Germany has lagged behind many other countries on the issue. Germany was selected as the research site because compared to other European countries, it accepted the largest number of refugees in 2015-2016. Additionally, its highly regulated labour market and well-established dual apprenticeship system makes formal skills recognition particularly relevant for refugees who only possess non-formally and informally acquired vocational skills (NFIVOS) as such recognition would enable these individuals to access skilled jobs that in Germany typically require formal vocational or professional qualifications. In order to explore the impeding and facilitating factors in the recognition of refugees’ NFIVOS for use in Germany’s labour market, this study used unstructured informant interviews with refugees (N=7), semi-structured respondent interviews with people working on skills recognition and refugees at the operational and strategic levels (N=53), observations of advisory sessions for foreigners with NFIVOS or foreign credentials (N=14) and document analysis (N=49). In particular, this research focused on 14 case studies composed of seven refugees and seven skills assessment and recognition arrangements in Germany’s federal state of Baden-Württemberg. The data from this study were analysed using Bourdieu’s theory of practice (1977b, 1986) with its concepts of field, capital and habitus. In so doing, it became clear that the biggest infrastructural barrier to the formal recognition of refugees’ NFIVOS was Germany’s lack of an arrangement that fulfilled this purpose in a refugee-friendly way. This could be seen as the result of Germany’s selective inclusion of foreign institutionalised habitus but exclusion of foreign embodied habitus (except when the latter was supplemented by a German institutionalised habitus) in the skills recognition procedures which transform foreign habitus into German institutionalised cultural capital. Given this lack of a refugee-friendly procedure, the study makes inferences from its 14 case studies about what could fill this gap and finds that potential facilitating factors are an interplay of Germany’s integration infrastructure and refugees’ personal agency. As a consequence, it is argued that refugees’ obstacles and facilitators in gaining formal skills recognition are the result of a mismatch and alignment, respectively, of refugees’ habitus with the requirements of Germany’s skills recognition field