Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner

The 'human topoisomerase I (htopoI) damage response' was reported to be triggered by various kinds of DNA lesions. Also, a high and persistent level of htopoI cleavage complexes correlated with apoptosis. In the present study, we demonstrate that DNA damage-independent induction of cell death using colcemid and tumor necrosis factor is also accompanied by a strong htopoI response that correlates with the onset of apoptotic hallmarks. Consequently, these results suggest that htopoI cleavage complex formation may be caused by signaling pathways independent of the kind of cellular stress. Thus, protein interactions or signaling cascades induced by DNA damage or cellular stress might lead to the formation of stabilized cleavage complexes rather than the DNA lesion itself. Finally, we show that p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid.

Higher-order non-linear analysis of steel structures. Part I : elastic second-order formulation

This paper presents a higher-order beam-column formulation that can capture the geometrically non-linear behaviour of steel framed structures which contain a multiplicity of slender members. Despite advances in computational frame software, analyses of large frames can still be problematic from a numerical standpoint and so the intent of the paper is to fulfil a need for versatile, reliable and efficient non-linear analysis of general steel framed structures with very many members. Following a comprehensive review of numerical frame analysis techniques, a fourth-order element is derived and implemented in an updated Lagrangian formulation, and it is able to predict flexural buckling, snap-through buckling and large displacement post-buckling behaviour of typical structures whose responses have been reported by independent researchers. The solutions are shown to be efficacious in terms of a balance of accuracy and computational expediency. The higher-order element forms a basis for augmenting the geometrically non-linear approach with material non-linearity through the refined plastic hinge methodology described in the companion paper.

The human topoisomerase I damage response plays a role in apoptosis

Previous studies have shown that human topoisomerase I cleavage complexes form as a response to various DNA damages in vivo, the so called human topoisomerase I “damage response”. It was suggested that this damage response may play a role in DNA repair as well as in apoptosis, but only very few investigations have been done and the significance of the damage response still remains unclear. Here we demonstrate that human topoisomerase I cleavage complexes induced by high doses of UV irradiation are highly stable for up to 48 h. Furthermore, we show that human topoisomerase I cleavage complexes correlate with apoptosis. However, at low UV doses the cleavage complex level was very low and the complexes were repaired. Surprisingly, we found that high levels of stable cleavage complexes were not only found in UV-irradiated cells but also in untreated cells that underwent apoptosis. A possible role of human topoisomerase I in apoptosis is discussed.

Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Boken, berättelsen, pengarna I den digitala tidsåldern [The book, the story and the money in the digital age]

År 2012 är distribution av litteratur via internet inte längre en framtidsvision, utan ett etablerat format vid sidan av traditionella format som exempelvis pocketboken, den inbundna boken och ljudboken (AAP 2011; Amazon 2011; PaidContent 2011). Men den digitala tekniken etablerar inte enbart ett nytt format, utan förändrar också grundförutsättningarna för litterära konstformer och marknader. Detta kapitel behandlar en betydelsefull aspekt av denna förändring, nämligen hur den digitala tekniken påverkar relationen mellan läsare och författare och ökar läsarens inflytande över den kreativa processen. I den digitala tidsåldern är det möjligt att skapa berättelser online i en interaktiv process som involverar både läsare och författare. Kapitlet presenterar modeller för hur sådan “samproducerad e-litteratur” förändrar marknaden för litteratur och hur den påverkar den traditionella litteraturen.

Mobility and out-of-home activities of older people living in suburban environments : ‘Because I'm a driver, I don't have a problem'

Governments are challenged by the need to ensure that ageing populations stay active and engaged as they age. Therefore, it is critical to investigate the role of mobility in older people's engagement in out-of-home activities, and to identify the experiences they have within their communities. This research investigates the use of transportation by older people and its implications for their out-of-home activities within suburban environments. The qualitative, mixed-method approach employs data collection methods which include a daily travel diary (including a questionnaire), Global Positioning System (GPS) tracking and semi-structured interviews with older people living in suburban environments in Brisbane, Australia. Results show that older people are mobile throughout the city, and their car provides them with that opportunity to access desired destinations. This ability to drive allows older people to live independently and to assist others who do not drive, particularly where transport alternatives are not as accessible. The ability to transport goods and other people is a significant advantage of the private car over other transport options. People with no access to private transportation who live in low-density environments are disadvantaged when it comes to participation within the community. Further research is needed to better understand the relationship between transportation and participation within the community environment, to assist policy makers and city and transportation planners to develop strategies for age-friendly environments within the community.

Recasting the theory of mosquito-borne pathogen transmission dynamics and control

Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of theworld. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonald’s formula for R0 and its entomological derivative, vectorial capacity, are nowused to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the Ross–Macdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context formosquito blood feeding, themovement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control.

Social networks in arid Australia : a review of concepts and evidence

Arid systems are markedly different from non-arid systems. This distinctiveness extends to arid-social networks, by which we mean social networks which are influenced by the suite of factors driving arid and semi-arid regions. Neither the process of how aridity interacts with social structure, nor what happens as a result of this interaction, is adequately understood. This paper postulates three relative characteristics which make arid-social networks distinct: that they are tightly bound, are hierarchical in structure and, hence, prone to power abuses, and contain a relatively higher proportion of weak links, making them reactive to crisis. These ideas were modified from workshop discussions during 2006. Although they are neither tested nor presented as strong beliefs, they are based on the anecdotal observations of arid-system scientists with many years of experience. This paper does not test the ideas, but rather examines them in the context of five arid-social network case studies with the aim of hypotheses building. Our cases are networks related to pastoralism, Aboriginal outstations, the ‘Far West Coast Aboriginal Enterprise Network’ and natural resources in both the Lake-Eyre basin and the Murray–Darling catchment. Our cases highlight that (1) social networks do not have clear boundaries, and that how participants perceive their network boundaries may differ from what network data imply, (2) although network structures are important determinants of system behaviour, the role of participants as individuals is still pivotal, (3) and while in certain arid cases weak links are engaged in crisis, the exact structure of all weak links in terms of how they place participants in relation to other communities is what matters.

‘I came to this country for a better life’ : factors mediating employment trajectories among young people who migrated to Australia as refugees during adolescence

Located at the intersection of two vulnerable groups in the contemporary labour market, young people who migrate as refugees during adolescence face a unique constellation of opportunities and challenges that shape their employment trajectories. Yet the tendency for research to focus on the early years of refugee settlement means that we have an inadequate understanding the factors that mediate their employment decisions, experiences and outcomes. Based on interviews with 51 young people, this article explores how aspirations, responsibilities, family, education and networks are understood to influence the employment trajectories of adolescent refugee migrants. While this article draws attention to the complex and dynamic range of challenges and constraints that these young people negotiate in the pursuit of satisfying and sustainable employment, what also emerges is an optimistic and determined cohort who, even as they at times unsuccessfully prepare for and navigate the labour market, maintain high hopes for a better life.

Should I stay or should I go? The challenges and opportunities of moving between university systems

The scientific job market has evolved to a truly globalized market. This is epitomized not only by the English language being the de facto scientific language but also by the increasing share of native language journals that are being offered in multiple languages or have or will fully converted to English (such as, for example, the BISE journal in 2015). Similarly, a plethora of exchange programs exists that allow students and academic staff to visit other institutions and exchange knowledge, ideas, and learning opportunities. While student migration across scientific institutions is an established phenomenon (Gribble, 2008) with ample structures, policies, and schemes such as ERASMUS1 in place, academic staff migration between countries is still a challenge, even if exchange programs exist (Enders, 1998). One reason may be that different career paths, varying teaching loads and different evaluation schemes for what constitutes scientific excellence are notable. This also influences the decision of where to start and continue an academic career. While the university systems themselves have been examined previously (Galliers and Whitley, 2007; Lyytinen et al., 2007) and while there is knowledge about career requirements in different university systems (Dennis et al., 2006; Dean et al., 2011; Loos et al., 2013; Recker, 2013), we still do not know much about individual and contextual decisions of academics that either consider or execute a migration between university systems.

Crypto Topics and Applications I

In this chapter, we discuss four related areas of cryptology, namely, authentication, hashing, message authentication codes (MACs), and digital signatures. These topics represent active and growing research topics in cryptology. Space limitations allow us to concentrate only on the essential aspects of each topic. The bibliography is intended to supplement our survey. We have selected those items which providean overview of the current state of knowledge in the above areas. Authentication deals with the problem of providing assurance to a receiver that a communicated message originates from a particular transmitter, and that the received message has the same content as the transmitted message. A typical authentication scenario occurs in computer networks, where the identity of two communicating entities is established by means of authentication. Hashing is concerned with the problem of providing a relatively short digest–fingerprint of a much longer message or electronic document. A hashing function must satisfy (at least) the critical requirement that the fingerprints of two distinct messages are distinct. Hashing functions have numerous applications in cryptology. They are often used as primitives to construct other cryptographic functions. MACs are symmetric key primitives that provide message integrity against active spoofing by appending a cryptographic checksum to a message that is verifiable only by the intended recipient of the message. Message authentication is one of the most important ways of ensuring the integrity of information that is transferred by electronic means. Digital signatures provide electronic equivalents of handwritten signatures. They preserve the essential features of handwritten signatures and can be used to sign electronic documents. Digital signatures can potentially be used in legal contexts.

“I drove after drinking alcohol” and other risky driving behaviours reported by young novice drivers in Queensland, Australia

Background. Volitional risky driving behaviours such as drink- and drug-driving (i.e. substance-impaired driving) and speeding contribute to the overrepresentation of young novice drivers in road crash fatalities, and crash risk is greatest during the first year of independent driving in particular. Aims. To explore the: 1) self-reported compliance of drivers with road rules regarding substance-impaired driving and other risky driving behaviours (e.g., speeding, driving while tired), one year after progression from a Learner to a Provisional (intermediate) licence; and 2) interrelationships between substance-impaired driving and other risky driving behaviours (e.g., crashes, offences, and Police avoidance). Methods. Drivers (n = 1,076; 319 males) aged 18-20 years were surveyed regarding their sociodemographics (age, gender) and self-reported driving behaviours including crashes, offences, Police avoidance, and driving intentions. Results. A relatively small proportion of participants reported driving after taking drugs (6.3% of males, 1.3% of females) and drinking alcohol (18.5% of males, 11.8% of females). In comparison, a considerable proportion of participants reported at least occasionally exceeding speed limits (86.7% of novices), and risky behaviours like driving when tired (83.6% of novices). Substance-impaired driving was associated with avoiding Police, speeding, risky driving intentions, and self-reported crashes and offences. Forty-three percent of respondents who drove after taking drugs also reported alcohol-impaired driving. Discussion and Conclusions. Behaviours of concern include drink driving, speeding, novice driving errors such as misjudging the speed of oncoming vehicles, violations of graduated driver licensing passenger restrictions, driving tired, driving faster if in a bad mood, and active punishment avoidance. Given the interrelationships between the risky driving behaviours, a deeper understanding of influential factors is required to inform targeted and general countermeasure implementation and evaluation during this critical driving period. Notwithstanding this, a combination of enforcement, education, and engineering efforts appear necessary to improve the road safety of the young novice driver, and for the drink-driving young novice driver in particular.

The SCRAMSPACE I scramjet flight design and construction

The design activities of the development of the SCRAMSPACE I scramjet-powered free-flight experiment are described in this paper. The objectives of this flight are first described together with the definition of the primary, secondary and tertiary experiments. The Scramjet configuration studied is first discussed together with the rocket motor system selected for this flight. The different flight sequences are then explained, highlighting the SCRAMSPACE I free-flyer separation and re-orientation procedures. A design trade-off study is then described considering vehicle stability, packaging, thermo-structural analysis and trajectory, discussing the alignment of the predicted performance with the mission scientific requirements. The global system architecture and instrumentation of the vehicle are then explained. The conclusions of this design phase are that a vehicle design has been produced which is able to meet the mission scientific goals and the procurement & construction of the vehicle are ongoing.

It’s not only what I think but what they think! The moderating effect of social norms

The current research extends our knowledge of the main effects of attitude, subjective norm, and perceived control over the individual’s technology adoption. We propose a critical buffering role of social influence on the collectivistic culture in the relationship between attitude, perceived behavioral control, and Information Technology (IT) adoption. Adoption behavior was studied among 132 college students being introduced to a new virtual learning system. While past research mainly treated these three variables as being in parallel relationships, we found a moderating role for subjective norm on technology attitude and perceived control on adoption intent. Implications and limitations for understating the role of social influence in the collectivistic society are discussed.