Single-stranded DNA-binding protein hSSB1 is critical for genomic stability

Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

Motivating domestic energy conservation through comparative, community-based feedback in mobile and social media

The progress of technology has led to the increased adoption of energy monitors among household energy consumers. While the monitors available on the market deliver real-time energy usage feedback to the consumer, the format of this data is usually unengaging and mundane. Moreover, it fails to address consumers with different motivations and needs to save and compare energy. This paper presents a study that seeks to provide initial indications for motivation-specific design of energy-related feedback. We focus on comparative feedback supported by a community of energy consumers. In particular, we examine eco-visualisations, temporal self-comparison, norm comparison, one-on-one comparison and ranking, whereby the last three allow us to explore the potential of socialising energy-related feedback. These feedback types were integrated in EnergyWiz – a mobile application that enables users to compare with their past performance, neighbours, contacts from social networking sites and other EnergyWiz users. The application was evaluated in personal, semi-structured interviews, which provided first insights on how to design motivation-related comparative feedback.

The patella morphology in trochlear dysplasia : a comparative MRI study

BACKGROUND: Trochlear dysplasia is suspected to have a genetic basis and causes recurrent patellar instability due to insufficient anatomical geometry. Numerous studies about trochlear morphology and the optimal surgical treatment have been carried out, but no attention has been paid to the corresponding patellar morphology.----- ----- PURPOSE: The aim of this study was the evaluation of the patellar morphology in normal and trochlear dysplastic knees. ----- ----- STUDY DESIGN: Biometric analysis. ----- ----- METHODS: Twenty two patellae with underlying trochlear dysplasia (study group--SG) were compared with 22 matched knees with normal trochlear shape (control group--CG) on transverse and sagittal MRI slices. We compared transverse diameter, cartilaginous thickness, Wiberg-index and -angle, length and radius of lateral and medial facet, patellar shape and angle, retropatellar length, and type of trochlear dysplasia. For statistical analysis we used the Wilcoxon signed ranks test. ----- ----- RESULTS: The transverse and sagittal diameter, mean length of medial patellar facet, and mean cartilaginous and subchondral Wiberg-index showed statistical differences between the two groups. ----- ----- CONCLUSIONS: Although the insufficient trochlear depth and decreased lateral trochlear slope are responsible for patellofemoral instability, the patella shows morphological changes in trochlear dysplastic knees. Its overall size and the medial facet are smaller. Although the femoral sulcus angle is larger, the Wiberg-angle and -index are equal to the control group. This may indicate that the patellar morphology may not be a result of missing medial patellofemoral pressure in trochlear dysplastic knees, but a decreased medial patellofemoral traction. This seems to be caused by hypotrophic medial patellofemoral restraints in combination with an increased lateral patellar tilt, both resulting in a decreased tension onto the medial patella facet. Whether there is a genetic component to the patellar morphology remains open.

A comparative study of mesoporous-glass/silk and non-mesoporous-glass/silk scaffolds : physiochemistry and in vivo osteogenesis

Mesoporous bioactive glass (MBG) is a new class of biomaterials with a well-ordered nanochannel structure, whose in vitro bioactivity is far superior than that of non-mesoporous bioactive glass (BG); the material's in vivo osteogenic properties are, however, yet to be assessed. Porous silk scaffolds have been used for bone tissue engineering, but this material's osteoconductivity is far from optimal. The aims of this study were to incorporate MBG into silk scaffolds in order to improve their osteoconductivity and then to compare the effect of MBG and BG on the in vivo osteogenesis of silk scaffolds. MBG/silk and BG/silk scaffolds with a highly porous structure were prepared by a freeze-drying method. The mechanical strength, in vitro apatite mineralization, silicon ion release and pH stability of the composite scaffolds were assessed. The scaffolds were implanted into calvarial defects in SCID mice and the degree of in vivo osteogenesis was evaluated by microcomputed tomography (μCT), hematoxylin and eosin (H&E) and immunohistochemistry (type I collagen) analyses. The results showed that MBG/silk scaffolds have better physiochemical properties (mechanical strength, in vitro apatite mineralization, Si ion release and pH stability) compared to BG/silk scaffolds. MBG and BG both improved the in vivo osteogenesis of silk scaffolds. μCT and H&E analyses showed that MBG/silk scaffolds induced a slightly higher rate of new bone formation in the defects than did BG/silk scaffolds and immunohistochemical analysis showed greater synthesis of type I collagen in MBG/silk scaffolds compared to BG/silk scaffolds.

Mobility, accessibility and activity participation : a comparative assessment of methods to identify rural transport disadvantage

Traditionally, transport disadvantage has been identified using accessibility analysis although the effectiveness of the accessibility planning approach to improving access to goods and services is not known. This paper undertakes a comparative assessment of measures of mobility, accessibility, and participation used to identify transport disadvantage using the concept of activity spaces. A 7 day activity-travel diary data for 89 individuals was collected from two case study areas located in rural Northern Ireland. A spatial analysis was conducted to select the case study areas using criteria derived from the literature. The criteria are related to the levels of area accessibility and area mobility which are known to influence the nature of transport disadvantage. Using the activity-travel diary data individuals weekly as well as day to day variations in activity-travel patterns were visualised. A model was developed using the ArcGIS ModelBuilder tool and was run to derive scores related to individual levels of mobility, accessibility, and participation in activities from the geovisualisation. Using these scores a multiple regression analysis was conducted to identify patterns of transport disadvantage. This study found a positive association between mobility and accessibility, between mobility and participation, and between accessibility and participation in activities. However, area accessibility and area mobility were found to have little impact on individual mobility, accessibility, and participation in activities. Income vis-àvis ´ car-ownership was found to have a significant impact on individual levels of mobility, and accessibility; whereas participation in activities were found to be a function of individual levels of income and their occupational status.

A comparative analysis of business analysis (BA) and business process management (BPM) capabilities

Many initiatives to improve Business processes are emerging. The essential roles and contributions of Business Analyst (BA) and Business Process Management (BPM) professionals to such initiatives have been recognized in literature and practice. The roles and responsibilities of a BA or BPM practitioner typically require different skill-sets; however these differences are often vague. This vagueness creates much confusion in practice and academia. While both the BA and BPM communities have made attempts to describe their domains through capability defining empirical research and developments of Bodies of knowledge, there has not yet been any attempt to identify the commonality of skills required and points of uniqueness between the two professions. This study aims to address this gap and presents the findings of a detailed content mapping exercise (using NVivo as a qualitative data analysis tool) of the International Institution of Business Analysis (IIBA®) Guide to the Business Analysis Body of Knowledge (BABOK® Guide) against core BPM competency and capability frameworks.

Consumers’ intentions to adopt 3G in regional cities in China : a comparative study

Rapid mobile technological evolution and the large economic stake in commercial development of mobile technological innovation make it necessary to understand consumers' motivations towards the latest advanced and updated technologies and services. 3G (the third generation of mobile communication technology) recently started its commercial development in the world‘s largest mobile communication market, China, after being delayed for a few years. Although China fell behind in commercially developing 3G, it is difficult to ignore studying this area, given the size of the market and promising future developments. This market deserves focused research attention, especially in terms of consumer behaviour towards the adoption of mobile technological innovation. Thus, the program of research in this thesis was designed to investigate how Chinese consumers respond to the use of this newly launched mobile technological innovation, with a focus on what factors affect their 3G adoption intentions. It aimed to yield important insights into Chinese consumers‘ innovation adoption behaviours and to contribute to marketing and innovation adoption research. Furthermore, it has been documented that Chinese consumers vary widely between regions in dialect, lifestyle, culture, purchasing power and consumption attitudes. Based on economic development and local culture, China can be divided geographically into distinctive regional consumer markets. Consequently, the results of consumer behaviour research in one region may not necessarily be extrapolated to other regions. In order to better understand Chinese consumers, the disparities between regions should not be overlooked. Therefore, another objective of this program of research was to examine regional variances in consumers' innovation adoption, specifically to identify the similarities and differences in factors influencing 3G adoption, contributing to intra-cultural studies. An extensive literature review identified two gaps: current China-based innovation adoption research studies are limited in providing adequate prediction and explanation of Chinese consumers' intentions to adopt 3G; and there was limited knowledge about the differences between regional Chinese consumers in innovation adoption. Two research questions therefore were developed to address these gaps: 1) What factors influence Chinese consumers' intentions to adopt 3G? 2) How do Chinese consumers differ between regional markets in the relative influence of the factors in determining their intentions to adopt 3G? In accordance with postpositivist research philosophy, two studies were designed to answer the research questions, using mixed methods. To meet the research objectives, the two studies were both conducted in three regional cities, namely Beijing, Shanghai and Wuhan, centred in the three regions of North China, East China and Central China respectively, with sufficient cultural and economical regional variances. Study One was an exploratory study with qualitative research methods. It involved 45 in-depth interviews in the three research cities to gain rich insights into the research context from natural settings. Eight important concepts related to 3G adoption were generated from analysis of the interview data, namely utilitarian expectation, hedonic expectation, status gains, status loss avoidance, normative influence, external influence, cost and quality concern. The concepts of social loss avoidance and quality concern were two unique findings, whereas the other concepts were similar to the findings in Western innovation adoption studies. Moreover, variances in 3G adoption between three groups of regional consumers were also identified, focusing on the perceptions of two concepts, namely status gains and normative influence. The conceptual research model was then developed incorporating the eight concepts plus the dependent variable of adoption intention. The hypothesized relationships between the nine constructs and hypotheses about the differences between regional consumers in 3G adoption were informed by the findings of Study One and the literature reviewed. Study Two was a quantitative study involving a web-based survey and statistical analysis procedure. The web-based survey attracted 800 residents from the three research cities, 270 from Beijing, 265 from Shanghai and 265 from Wuhan. They comprised three research samples for this study and consequently three sets of data were obtained. The data was analysed by Structural Equation Modelling together with Multi-group Analysis. The analysis confirmed that the concepts generated in Study One were influential factors affecting Chinese consumers' 3G adoption intention, with the exception of the concept external influence. Differences were found between the samples in the three research cities in the effect of hedonic expectation, status gains, status loss avoidance and normative influence on 3G adoption intention. The two Studies undertaken in this thesis contributed a better understanding of Chinese consumers' intentions to adopt advanced mobile technological innovation, namely 3G, in three regional markets. This knowledge contributes to innovation adoption and intra-cultural research, as well as consumer behaviour theory. It is also able to inform international and domestic telecommunication companies to develop and deliver more effective marketing strategies across Chinese regional markets. Limitations in the research were identified in terms of the sampling techniques used and the design of the two Studies. Future research was suggested in other Chinese regional markets and into consumer adoption of other types of mobile technological innovations.