An adjoint for likelihood maximization

The process of likelihood maximization can be found in many different areas of computational modelling. However, the construction of such models via likelihood maximization requires the solution of a difficult multi-modal optimization problem involving an expensive O(n3) factorization. The optimization techniques used to solve this problem may require many such factorizations and can result in a significant bottle-neck. This article derives an adjoint formulation of the likelihood employed in the construction of a kriging model via reverse algorithmic differentiation. This adjoint is found to calculate the likelihood and all of its derivatives more efficiently than the standard analytical method and can therefore be utilised within a simple local search or within a hybrid global optimization to accelerate convergence and therefore reduce the cost of the likelihood optimization

Effect of 2-H and 18-O water isotopes in kinesin-1 gliding assay

We show here the effects of heavy-hydrogen water (^2^H~2~O) and heavy-oxygen water (H~2~^18^O) on the gliding speed of microtubules on kinesin-1 coated surfaces. Increased fractions of isotopic waters used in the motility solution decreased the gliding speed of microtubules by a maximum of 21% for heavy-hydrogen and 5% for heavy-oxygen water. We discuss possible interpretations of these results and the importance for future studies of water effects on kinesin and microtubules. We also discuss the implication for biomolecular devices incorporating molecular motors

Speed effects in gliding motility assays due to surface passivation, water isotope, and osmotic stress.

The molecular motor kinesin-1, an ATPase, and the substrate it walks along, microtubules, are vital components of eukaryotic cells. Kinesin converts chemical energy to linear motion as its two motor domains step along microtubules in a process similar to how we walk. Cells create systems of microtubules that direct the motion of kinesin. This directed motion allows kinesin to transport various cargos inside cells.

During the stepping process, the kinesin motor domains bind and unbind from their binding sites on the microtubules. Binding and unbinding rates of biomolecules are highly dependent on hydration and exclusion of water from the binding interface. Osmotic stress will likely strongly affect the binding and unbinding rates for kinesin and thus offers a tool to specifically probe those steps. We will report the effects of different osmolytes on microtubule speed and other observables in the gliding motility assay.

Kinesin’s kinetic core cycle hydrolyzes ATP with the help of a water molecule. Any modification to the water molecules the kinesin is in will change how ATP hydrolyzes and will ultimately affect how kinesin moves along microtubules. We will report preliminary results showing how kinesin is affected when the solvent it is in is changed from light water to heavy water.
 
When used in a surface assay or in devices, the kinesin and microtubule system is also dependent on substrate passivation. Kinesin motor domains do not transport microtubules in the gliding motility assay if kinesin is added to a glass microscope slide that has not been functionalized. Functionalization of the glass slides and slips is typically performed with bovine milk proteins called caseins. Bovine casein is a globular protein that can be broken up into four constituents: αs1, αs2, β, and κ. Each casein constituent affects how kinesin adheres to the glass and ultimately the speed at which microtubules are observed to glide at. Building on the work of Verma et.al., we have found that each constituent individually produces different outcomes in gliding assays. We will present these findings and discuss implications they have for use of gliding assays to study kinesin and use of kinesin-microtubule system in microdevices. 

[1] Chaen, S, N Yamamoto, I Shirakawa, and H Sugi. 2001. Effect of deuterium oxide on actomyosin motility in vitro. _Biochimica et biophysica acta_ 1506, no. 3: 218-23. 
[2] Vivek Verma, William O Hancock, Jeffrey M Catchmark, "The role of casein in supporting the operation of surface bound kinesin," _J. Biol. Eng._ 2008; 2: 14.

Acknowledgements: This work was supported by the DTRA CB Basic Research Program under Grant No. HDTRA1-09-1-008.
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The significant other: the value of jewellery within the conception, design and experience of body focussed digital devices

In this paper, we demonstrate how craft practice in contemporary jewellery opens up conceptions of ‘digital jewellery’ to possibilities beyond merely embedding pre-existing behaviours of digital systems in objects, which follow shallow interpretations of jewellery. We argue that a design approach that understands jewellery only in terms of location on the body is likely to lead to a world of ‘gadgets’, rather than anything that deserves the moniker ‘jewellery’. In contrast, by adopting a craft approach, we demonstrate that the space of digital jewellery can include objects where the digital functionality is integrated as one facet of an object that can be personally meaningful for the holder or wearer.</p

The development of an innovative mobile phone app for type 1 diabetes alcohol education

Introduction Social media is being increasingly used to try and engage young people with their healthcare issues. However, most mobile diabetes applications (Apps) do not include personalised patient education, a key facet of diabetes self-management. We sought the views and ideas of young people with type 1 diabetes to enable the design of innovative new Apps which might help to improve their quality of life. This project highlights an innovative, patient-centric approach to the development and production of a health based mobile App concerning diabetes education about alcohol. Methods Data collected by semi-structured, in-depth qualitative interviews (n=9) of people with type 1 diabetes aged 18-21. Interviews were transcribed and loaded onto the qualitative data analysis tool NVivo. Baseline data analysis was undertaken to locate potential ideas for mobile App development, with suggestions chosen needing to reflect interviewee requirements and to meet clinic goals. Results Interviewees suggested that they would find a guide which could be accessed via a mobile device about alcohol limits and the effects of alcohol on their diabetes particularly useful on a night out. An App about alcohol and diabetes, ‘Start Safe, Stay Safe’, was developed with further input from young people with type 1 diabetes and clinic staff. Summary In developing a mobile App about alcohol and diabetes, we have shown how young people with type 1 diabetes can participate effectively in the design and implementation of new technology which they can then use to improve their quality of life

Reconsidering your perceptions: exploring the lifeworld of a young person with type 1 diabetes

Introduction Views of young people with type 1 diabetes are vital in developing quality services, yet research on their lifestyle and use of web and mobile technology to support their condition is sparse. We aimed to develop a deeper understanding of the perspective of a young person with type 1 diabetes and construct a picture of their lifeworld. Methods Data collected by semi-structured, in-depth qualitative interviews (n=9) of people with type 1 diabetes aged 18-21. Interviews were transcribed and loaded onto the qualitative data analysis tool NVivo. Results A number of themes emerged, including: • The effects of technology on living with diabetes. • Use of social media, mobile phones and Apps to obtain information and support. • Feelings about the health services they used. We also uncovered several interesting issues that concern patients in this age group: • Understanding the isolation that young people might feel at this age. • Personal attitudes to type 1 diabetes and initiating improvement. • Fear, discomfort and being seen as different. • Why we might embrace and show negative views of the condition. • Rethinking the use of Facebook. Summary We obtained a deeper and more empathetic understanding of the feelings of young people with type 1 diabetes, and the issues that are important to them. This data will be used to look at local services, producing more effective systems for support and self-management which take into account the feelings of patients and make them more likely to engage with technology

Why haven’t YOU thought of that? Over 15 great mobile app ideas for improving the quality of life of a young person with type 1 diabetes

Introduction The use of mobile devices to look up health-related information is of increasing importance to young people, who have a radically different view of technology than either their parents or practitioners. We explored what young people with type 1 diabetes required from social media and mobile technology by seeking their views and ideas, enabling the eventual design of innovative new tools to help them engage with health services and their own health in their preferred manner. Methods Data collected by semi-structured, in-depth qualitative interviews (n=9) of people with type 1 diabetes aged 18-21. Interviews were transcribed and loaded onto the qualitative data analysis tool NVivo. Baseline data analysis was then undertaken to locate potential ideas for mobile App development. Results Over fifteen innovative new ideas for mobile Apps not currently available were suggested including: • Twitter - contacting other people with type 1 diabetes, an emergency link for contacting the health service and receiving direct messages from clinic staff which would help to personalise diabetes care. • Hypoglycaemia awareness - advice on what to do for friends, family and colleagues who might come into contact with the participant. • Illness information. • News/information on existing/new diabetes technology. Summary We have explored what young people with type 1 diabetes want from social media and mobile technology, so that the design and implementation of new technology to help self-management is more patient-centred, more likely to be used and more likely to improve quality of life