14-3-3 proteins and the p53 family : a study in keratinocytes

Several associations between 14-3-3 proteins and members of the p53 family have been revealed. However, numerous questions regarding 14-3-3 proteins, p53 family members and the relationships between thetwo families remain. This thesis contributes to answer these questions. Downregulation of 14-3-3_ increased the propensity for DNA-damage induced apoptosis and increased cell-cell contacts, two characteristics that are often lost in cancer cells. Differences between 14-3-3_ and 14-3-3_ in nucleocytoplasmic shuttling have been described. The difference innucleocytoplasmic shuttling likely forms a basis for specialized biological functions of the 14-3-3 isoforms. Keratinocyte specific p53 regulated G2cell-cycle arrest and the lack of a contribution for 14-3-3_ in this cell-type has been observed, whereas 14-3-3_ induction clearly plays a distinct role in G2 arrest in other cell-types. An improved method for detecting p53 induced apoptosis by flow cytometry is portrayed by expressing a duplicated GFP protein. This double GFP protein can be used for future research in the fields of 14-3-3 and p53. A widely used method to detect and quantify p73 splice-variant expression is critically assessed. It turns out that, using this method it is not possible to accurately quantify p73splice-variants.Tebu-bio Nederland Leids Universiteits Fonds BD Biosciences NederlandUBL - phd migration 201

Designing for multi-user interaction in the home environment: Implementing social translucence

© 2016 ACM. Interfaces of interactive systems for domestic use are usually designed for individual interactions although these interactions influence multiple users. In order to prevent conflicts and unforeseen influences on others we propose to leverage the human ability to take each other into consideration in the interaction. A promising approach for this is found in the social translucence framework, which was originally described by Erickson & Kellogg. In this paper, we investigate how to design multi-user interfaces for domestic interactive systems through two design cases where we focus on the implementation of social translucence constructs (visibility, awareness, and accountability) in the interaction. We use the resulting designs to extract design considerations: interfaces should not prescribe behavior, need to offer sufficient interaction alternatives, and previous settings need to be retrievable. We also identify four steps that can be integrated in any design process to help designers in creating interfaces that support multi-user interaction through social translucence

First-principles elucidation of the surface chemistry of the C2Hx (x = 0–6) adsorbate series on Fe(100)

Ab initio total-energy calculations of the elementary reaction steps leading to acetylene, ethylene and ethane formation and their decomposition on Fe(100) are described. Alongside the endothermicity of all the formation reactions, the crucial role played by adsorbed ethyl as main precursor towards both ethylene and ethane formation, characterises Fe(100) surface reactivity towards C2Hx (x = 0–6) hydrocarbon formation in the low coverage limit. A comprehensive scheme based on three viable mechanisms towards ethyl formation on Fe(100), including methyl/methylene coupling, methyl/methylidyne coupling followed by one hydrogenation and methyl/carbon coupling followed by two hydrogenations, is the main result of this article

Contribution of tenosynovitis of small joints to the symptom morning stiffness in patients presenting with undifferentiated and rheumatoid arthritis

Objective: Morning stiffness (MS) is characteristic of rheumatoid arthritis (RA). Despite its association with functional disability, the extent to which local inflammatory processes contribute to this symptom is unknown. Magnetic resonance imaging (MRI)-detected tenosynovitis of small joints is recognized as an early feature of RA, which is also associated with functional impairments. It has been proposed that tenosynovitis contributes to MS. Therefore, we assessed the relationship between MS and MRI-detected inflammation, in particular tenosynovitis. Method: In total, 286 consecutive patients newly presenting with undifferentiated arthritis and RA underwent contrast-enhanced 1.5 T MRI of (2–5) metacarpophalangeal, wrist, and (1–5) metatarsophalangeal joints. Scans were scored for tenosynovitis according to Haavardsholm, and for synovitis by Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). MS was dichotomized as ≥ 60 min or not. Associations between MS and tenosynovitis/synovitis were tested with logistic regression, data were categorized (solitary or simultaneous presence of synovitis/tenosynovitis), and the presence of an additive interaction was assessed. Results: MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS [80% vs 65%, odds ratio (OR) 2.11, 95% confidence interval (1.21;3.69)]. Synovitis was more often present in patients with MS [58% vs 44%, OR 1.79 (1.11;2.91)]. In categorized analyses, concurrent synovitis and tenosynovitis had the largest association [OR 2.43 (1.30;4.54)], in contrast to solitary synovitis [OR 0.85 (0.21;3.47)]. The additive interaction was non-significant. The variance explained in all analyses was small (range 4–5%). Conclusion: Tenosynovitis, combined with synovitis, at small joints is associated with MS and contributes to the pathophysiology of MS

Exploring the experiences and coping strategies of international medical students

<p>Abstract</p> <p>Background</p> <p>Few studies have addressed the challenges that international medical students face and there is a dearth of information on the behavioural strategies these students adopt to successfully progress through their academic program in the face of substantial difficulties of language barrier, curriculum overload, financial constraints and assessment tasks that require high proficiency in communication skills.</p> <p>Methods</p> <p>This study was designed primarily with the aim of enhancing understanding of the coping strategies, skill perceptions and knowledge of assessment expectations of international students as they progress through the third and fourth years of their medical degree at the School of Medicine, University of Tasmania, Australia.</p> <p>Results</p> <p>Survey, focus group discussion and individual interviews revealed that language barriers, communication skills, cultural differences, financial burdens, heavy workloads and discriminatory bottlenecks were key factors that hindered their adaptation to the Australian culture. Quantitative analyses of their examination results showed that there were highly significant (p < 0.001) variations between student performances in multiple choice questions, short answer questions and objective structured clinical examinations (70.3%, 49.7% & 61.7% respectively), indicating existence of communication issues.</p> <p>Conclusions</p> <p>Despite the challenges, these students have adopted commendable coping strategies and progressed through the course largely due to their high sense of responsibility towards their family, their focus on the goal of graduating as medical doctors and their support networks. It was concluded that faculty needs to provide both academic and moral support to their international medical students at three major intervention points, namely point of entry, mid way through the course and at the end of the course to enhance their coping skills and academic progression. Finally, appropriate recommendations were made.</p

FeP Nanocatalyst with Preferential [010] Orientation Boosts the Hydrogen Evolution Reaction in Polymer-Electrolyte Membrane Electrolyzer

The development of nonprecious metal electrocatalysts for polymer-electrolyte membrane (PEM) water electrolysis is a milestone for the technology, which currently relies on rare and expensive platinum-group metals. Half-cell measurements have shown iron phosphide materials to be promising alternative hydrogen evolution electrocatalysts, but their realistic performance in flow-through devices remains unexplored. To fill this gap, we report herein the activity and durability of FeP nanocatalyst under application-relevant conditions. Our facile synthesis route proceeds via impregnation of an iron complex on conductive carbon support followed by phosphorization, giving rise to highly crystalline nanoparticles with predominantly exposed [010] facets, which accounts for the high electrocatalytic activity. The performance of FeP gas diffusion electrodes toward hydrogen evolution was examined under application-relevant conditions in a single cell PEM water electrolysis at 22 °C. The FeP cathode exhibited a current density of 0.2 A cm–2 at 2.06 V, corresponding to a difference of merely 0.07 W cm–2 in power input as compared to state-of-the-art Pt cathode, while outperforming other nonprecious cathodes operated at similar temperature. Quantitative product analysis of our PEM device excluded the presence of side reactions and provided strong experimental evidence that our cell operates with 84–100% Faradaic efficiencies and with 4.1 kWh Nm–3 energy consumption. The FeP cathodes exhibited stable performance of over 100 h at constant operation, while their suitability with the intermittency of renewable sources was demonstrated upon 36 h operation at variable power inputs. Overall, the performance as well as our preliminary cost analysis reveal the high potential of FeP for practical applications.</p