Enterovirus71 (EV71) utilise host microRNAs to mediate host immune system enhancing survival during infection

Hand, Foot and Mouth Disease (HFMD) is a self-limiting viral disease that mainly affects infants and children. In contrast with other HFMD causing enteroviruses, Enterovirus71 (EV71) has commonly been associated with severe clinical manifestation leading to death. Currently, due to a lack in understanding of EV71 pathogenesis, there is no antiviral therapeutics for the treatment of HFMD patients. Therefore the need to better understand the mechanism of EV71 pathogenesis is warranted. We have previously reported a human colorectal adenocarcinoma cell line (HT29) based model to study the pathogenesis of EV71. Using this system, we showed that knockdown of DGCR8, an essential cofactor for microRNAs biogenesis resulted in a reduction of EV71 replication. We also demonstrated that there are miRNAs changes during EV71 pathogenesis and EV71 utilise host miRNAs to attenuate antiviral pathways during infection. Together, data from this study provide critical information on the role of miRNAs during EV71 infection.

Older driver safety and mobility : where to from here?

The older adult population (65 years and over) represents a rapid growing segment of the population in many developed countries. Unlike earlier cohorts of older drivers that included many who were familiar with public transportation, the present cohort of older drivers historically has a greater reliance on the private automobile as their main form of transportation. Recent studies of older adults’ travel patterns reported automobile to be responsible for over 80% of the total number of hours spent on all trips. While older drivers, as a group, does not demonstrate a particular road risk, the evident demographic change and the increased physical fragility and severity of crash-related injuries makes older driver safety a prevalent public health issue. This study systematically reviewed the safety and mobility outcomes of existing strategies used internationally to manage older driver safety, with a specific focus on age-based testing (ABT), license restriction and self-regulation (i.e. voluntary limiting driving in potentially hazardous situations). ABT remains the most commonly adopted strategy by licensing authorities both within Australia and internationally. Heterogeneity in the development of functional declines, and in driving behaviours within the older driver population, makes age an unreliable index of driving capacity. Given the counter-productive safety and mobility outcomes of ABT strategies, their continued popularity within both the legislative and public domains remains problematic. Self-regulation may provide greater potential for reducing older drivers’ crash risk while maintaining their mobility and independence. The current body of literature on older drivers’ self-regulation is systematically reviewed. Despite being promoted by researchers and licensing authorities as a strategy to maintain older driver safety and mobility, the proportion of older drivers who self-regulate, and exactly how they do so, remains unclear. Future research on older drivers’ adoption of self-regulation, particularly the underlying psychological factors that underlies this process, is needed in order to promote its use within the older driver community.

Sedation breaks : are they good for the critically ill patient? A review.

Background:  Tradition has led us to believe that a heavily sedated patient is a comfortable, settled, compliant patient for whom sedation will improve outcome. The current move witnessed in clinical practice today of limiting sedation has led health care in recent years to question the benefit and necessity of routine, continuous sedation for all patients requiring mechanical ventilation. However, as a result there has been a rise in the amount of agitation being reported as being experienced by patients with the daily withdrawal of sedation. Aims:  The purpose of this paper is to review current arguments for and against perserving with agitation versus re-sedating, when it presents during the daily sedation breaks. Findings:  Of the literature reviewed, the question to re-sedate the mechanically ventilated agitated patient during sedation breaks remains an issue of contention. Although there is evidence focusing on the psychological effects of long-term sedation and sedation breaks specifically, the complex nature of critical illness in some cases means that individualized care is of paramount importance and in-depth assessment is crucial when deciding to re-sedate in the face of undetermined agitation. Agitation has been closely linked with several incidents that can be detrimental to patient safety, such as removal of lines and unplanned self-extubation. Conclusion:  The recommendations of this review are that nurses should re-commence sedation if the patient becomes agitated following a sedation break. Aims:  The purpose of this paper is to review current arguments for and against perserving with agitation versus re-sedating, when it presents during the daily sedation breaks. Findings:  Of the literature reviewed, the question to re-sedate the mechanically ventilated agitated patient during sedation breaks remains an issue of contention. Although there is evidence focusing on the psychological effects of long-term sedation and sedation breaks specifically, the complex nature of critical illness in some cases means that individualized care is of paramount importance and in-depth assessment is crucial when deciding to re-sedate in the face of undetermined agitation. Agitation has been closely linked with several incidents that can be detrimental to patient safety, such as removal of lines and unplanned self-extubation. Conclusion:  The recommendations of this review are that nurses should re-commence sedation if the patient becomes agitated following a sedation break.

Jacobian-free Newton-Krylov methods with GPU acceleration for computing nonlinear ship wave patterns

The nonlinear problem of steady free-surface flow past a submerged source is considered as a case study for three-dimensional ship wave problems. Of particular interest is the distinctive wedge-shaped wave pattern that forms on the surface of the fluid. By reformulating the governing equations with a standard boundary-integral method, we derive a system of nonlinear algebraic equations that enforce a singular integro-differential equation at each midpoint on a two-dimensional mesh. Our contribution is to solve the system of equations with a Jacobian-free Newton-Krylov method together with a banded preconditioner that is carefully constructed with entries taken from the Jacobian of the linearised problem. Further, we are able to utilise graphics processing unit acceleration to significantly increase the grid refinement and decrease the run-time of our solutions in comparison to schemes that are presently employed in the literature. Our approach provides opportunities to explore the nonlinear features of three-dimensional ship wave patterns, such as the shape of steep waves close to their limiting configuration, in a manner that has been possible in the two-dimensional analogue for some time.

Effectiveness of reactive power capability of photo voltaic inverters to maintain voltage profile in a residential distribution feeder

Large penetration of rooftop PVs has resulted in unacceptable voltage profile in many residential distribution feeders. Limiting real power injection from PVs to alleviate over voltage problem is not feasible due to loss of green power and hence corresponding revenue loss. Reactive capability of the PV inverter can be a solution to address over voltage and voltage dip problems to some extent. This paper proposes an algorithm to utilize reactive capability of PV inverters and investigate their effectiveness for voltage improvement based on R/X ratio of the feeder. The length and loading level of the feeder for a particular R/X ratio to have acceptable voltage profile is also investigated. This can be useful for suburban design and residential distribution planning. Furthermore, coordination among different PVs using residential smart meters via a substation based controller is also proposed.

Geo-locked photo sharing on mobile devices

We introduce the idea of geo-locking through a mobile phone based photo sharing application called Picalilly (figure 1). Using its geo-locking feature, Picalilly allows its users to manually define geographical boundaries for sharing photos -- limiting sharing within user-defined boundaries as well as facilitating open sharing between strangers within such boundaries. To explore the potential of geo-locking, we carried out a small scale field trial of Picalilly involving two groups of students, who were part of a two-week long introduction program at a university. Our preliminary results show that Picalilly facilitated 1) sharing of 'places' and 2) localized explorations.

Mid-Holocene sea-level and coral reef demise : U-Th dating of subfossil corals in Moreton Bay, Australia

It is increasingly apparent that sea-level data (e.g. microfossil transfer functions, dated coral microatolls and direct observations from satellite and tidal gauges) vary temporally and spatially at regional to local scales, thus limiting our ability to model future sea-level rise for many regions. Understanding sealevel response at ‘far-field’ locations at regional scales is fundamental for formulating more relevant sea-level rise susceptibility models within these regions under future global change projections. Fossil corals and reefs in particular are valuable tools for reconstructing past sea levels and possible environmental phase shifts beyond the temporal constraints of instrumental records. This study used abundant surface geochronological data based on in situ subfossil corals and precise elevation surveys to determine previous sea level in Moreton Bay, eastern Australia, a far-field site. A total of 64 U-Th dates show that relative sea level was at least 1.1 m above modern lowest astronomical tide (LAT) from at least ˜6600 cal. yr BP. Furthermore, a rapid synchronous demise in coral reef growth occurred in Moreton Bay ˜5800 cal. yr BP, coinciding with reported reef hiatus periods in other areas around the Indo-Pacific region. Evaluating past reef growth patterns and phases allows for a better interpretation of anthropogenic forcing versus natural environmental/climatic cycles that effect reef formation and demise at all scales and may allow better prediction of reef response to future global change.

Remote sensing and core data needed to support planning and policy decision making

A variety of sustainable development research efforts and related activities are attempting to reconcile the issues of conserving our natural resources without limiting economic motivation while also improving our social equity and quality of life. Land use/land cover change, occurring on a global scale, is an aggregate of local land use decisions and profoundly impacts our environment. It is therefore the local decision making process that should be the eventual target of many of the ongoing data collection and research efforts which strive toward supporting a sustainable future. Satellite imagery data is a primary source of data upon which to build a core data set for use by researchers in analyzing this global change. A process is necessary to link global change research, utilizing satellite imagery, to the local land use decision making process. One example of this is the NASA-sponsored Regional Data Center (RDC) prototype. The RDC approach is an attempt to integrate science and technology at the community level. The anticipated result of this complex interaction between research and the decision making communities will be realized in the form of long-term benefits to the public.

Epidemiological and molecular features of dengue virus type-1 in New Caledonia, South Pacific, 2001–2013

Background The epidemiology of dengue in the South Pacific has been characterized by transmission of a single dominant serotype for 3–5 years, with subsequent replacement by another serotype. From 2001 to 2008 only DENV-1 was reported in the Pacific. In 2008, DENV-4 emerged and quickly displaced DENV-1 in the Pacific, except in New Caledonia (NC) where DENV-1 and DENV-4 co-circulated in 2008–2009. During 2012–2013, another DENV-1 outbreak occurred in NC, the third DENV-1 outbreak in a decade. Given that dengue is a serotype-specific immunizing infection, the recurrent outbreaks of a single serotype within a 10-year period was unexpected. Findings This study aimed to inform this phenomenon by examining the phylogenetic characteristics of the DENV-1 viruses in NC and other Pacific islands between 2001 and 2013. As a result, we have demonstrated that NC experienced introductions of viruses from both the Pacific (genotype IV) and South-east Asia (genotype I). Moreover, whereas genotype IV and I were co-circulating at the beginning of 2012, we observed that from the second half of 2012, i.e. during the major DENV-1 outbreak, all analyzed viruses were genotype I suggesting that a genotype switch occurred. Conclusions Repeated outbreaks of the same dengue serotype, as observed in NC, is uncommon in the Pacific islands. Why the earlier DENV-1 outbreaks did not induce sufficient herd immunity is unclear, and likely multifactorial, but the robust vector control program may have played a role by limiting transmission and thus maintaining a large susceptible pool in the population. Keywords: Dengue; Phylogeny; Genotype; Epidemics; New Caledonia

Free-riding, cooperation, and 'peaceful revolutions' in copyright

Modern copyright law is based on the inescapable assumption that users, given the choice, will free-ride rather than pay for access. In fact, many consumers of cultural works – music, books, films, games, and other works – fundamentally want to support their production. It turns out that humans are motivated to support cultural production not only by extrinsic incentives, but also by social norms of fairness and reciprocity. This article explains how producers across the creative industries have used this insight to develop increasingly sophisticated business models that rely on voluntary payments (including pay-what-you-want schemes) to fund their costs of production. The recognition that users are not always free-riders suggests that current policy approaches to copyright are fundamentally flawed. Because social norms are so important in consumer motivations, the perceived unfairness of the current copyright system undermines the willingness of people to pay for access to cultural goods. While recent copyright reform debate has focused on creating stronger deterrence through enforcement, increasing the perceived fairness and legitimacy of copyright law is likely to be much more effective. The fact that users will sometimes willingly support cultural production also challenges the economic raison d'être of copyright law. This article demonstrates how 'peaceful revolutions' are flipping conventional copyright models and encouraging free-riding through combining incentives and prosocial norms. Because they provide a means to support production without limiting the dissemination of knowledge and culture, there is good reason to believe that these commons-based systems of cultural production can be more efficient, more fair, and more conducive to human flourishing than conventional copyright systems. This article explains what we know about free-riding so far and what work remains to be done to understand the viability and importance of cooperative systems in funding cultural production.

Genomic organisation, activity and distribution analysis of the microbial putrescine oxidase degradation pathway

The catalytic action of putrescine specific amine oxidases acting in tandem with 4-aminobutyraldehyde dehydrogenase is explored as a degradative pathway in Rhodococcus opacus. By limiting the nitrogen source, increased catalytic activity was induced leading to a coordinated response in the oxidative deamination of putrescine to 4-aminobutyraldehyde and subsequent dehydrogenation to 4-aminobutyrate. Isolating the dehydrogenase by ion exchange chromatography and gel filtration revealed that the enzyme acts principally on linear aliphatic aldehydes possessing an amino moiety. Michaelis-Menten kinetic analysis delivered a Michaelis constant (KM=0.014mM) and maximum rate (Vmax=11.2μmol/min/mg) for the conversion of 4-aminobutyraldehyde to 4-aminobutyrate. The dehydrogenase identified by MALDI-TOF mass spectrometric analysis (E value=0.031, 23% coverage) belongs to a functionally related genomic cluster that includes the amine oxidase, suggesting their association in a directed cell response. Key regulatory, stress and transport encoding genes have been identified, along with candidate dehydrogenases and transaminases for the further conversion of 4-aminobutyrate to succinate. Genomic analysis has revealed highly similar metabolic gene clustering among members of Actinobacteria, providing insight into putrescine degradation notably among Micrococcaceae, Rhodococci and Corynebacterium by a pathway that was previously uncharacterised in bacteria.

Generalized aggregate Quality of Service computation for composite services

This article addresses the problem of estimating the Quality of Service (QoS) of a composite service given the QoS of the services participating in the composition. Previous solutions to this problem impose restrictions on the topology of the orchestration models, limiting their applicability to well-structured orchestration models for example. This article lifts these restrictions by proposing a method for aggregate QoS computation that deals with more general types of unstructured orchestration models. The applicability and scalability of the proposed method are validated using a collection of models from industrial practice.

Property : an instrumental institution for environmental governance

Property in an elusive concept. In many respects it has been regarded as a source of authority to use, develop and make decisions about whatever is the subject matter of this right of ownership. This is true whether the holder of this right of ownership is a private entity or a public entity. Increasingly a right of ownership of this kind has been recognised not only as a source of authority but also as a mechanism for restricting or limiting and perhaps even prohibiting existing or proposed activities that impact upon the environment. It is increasingly therefore an instrument of control as much as an instrument of authorisation. The protection and conservation of the environment are ultimately a matter of the public interest. This is not to suggest that the individual holders of rights of ownership are not interested in protecting the environment. It is open to them to do so in the exercise of a right of ownership as a source of authorisation. However a right of ownership – whether private or public – has become increasingly the instrument according to which the environment is protected and conserved. This article addresses these issues from a doctrinal as well as a practical perspective about how the environment is managed. It does so in five ways: ●considering briefly property as a concept ●reviewing property in its historical context ●analysing property as a human right ●examining property in natural resources ●reviewing judicial approaches to property in natural resources.

Desafios Para A Implementação Do Processo De Projeto Colaborativo: Análise Do Fator Humano

The ineffectiveness of current design processes has been well studied and has resulted in widespread calls for the evolution and development of new management processes. Perhaps one problem is that with the advent of BIM we are moving from one stage to another without necessarily having resolved all the issues. CAD design technology, if well handled, could have significantly raised the level of quality and efficiency of current processes, but in practice this was not fully realized. Therefore, technology alone can´t solve all the problems and the advent of BIM could result in a similar bottleneck. For a precise definition of the problem to be solved we should start by understanding what are the main current bottlenecks that have yet to be overcome by either new technologies or management processes, and the impact of human behavior related issues despite the advent of new technologies. The fragmented and dispersed nature of the AEC sector and the huge number of small organizations that comprise it would probably be a major limiting factor. Several authors have addressed this issue and more recently IDDS has been defined as the highest level of achievement. However, what is written on IDDS shows an extremely ideal situation on a state to be achieved; it shows a holistic utopian proposition with the intent to create the research agenda to move towards that state. Key to IDDS is the framing of a new management model which should address the problems associated with key aspects: technology, processes, policies and people. One of the primary areas to be further studied is the process of collaborative work and understanding, together with the development of proposals to overcome the many cultural barriers that currently exist and impede the advance of new management methods. The purpose of this paper is to define and delimit problems to be solved so that it is possible to implement a new management model for a collaborative design process.

Challenges for implementation of a new model of collaborative design management: Analyzing the impact of human factor

The ineffectiveness of current design processes has been well studied and has resulted in widespread calls for the evolution and development of new management processes. Even following the advent of BIM, we continue to move from one stage to another without necessarily having resolved all the issues. CAD design technology, if well handled, could have significantly raised the level of quality and efficiency of current processes, but in practice this was not fully realized. Therefore, technology alone can´t solve all the problems and the advent of BIM could result in a similar bottleneck. For a precise definition of the problem to be solved we should start by understanding what are the main current bottlenecks that have yet to be overcome by either new technologies or management processes, and the impact of human behaviour-related issues which impact the adoption and utilization of new technologies. The fragmented and dispersed nature of the AEC sector, and the huge number of small organizations that comprise it, are a major limiting factor. Several authors have addressed this issue and more recently IDDS has been defined as the highest level of achievement. However, what is written on IDDS shows an extremely ideal situation on a state to be achieved; it shows a holistic utopian proposition with the intent to create the research agenda to move towards that state. Key to IDDS is the framing of a new management model which should address the problems associated with key aspects: technology, processes, policies and people. One of the primary areas to be further studied is the process of collaborative work and understanding, together with the development of proposals to overcome the many cultural barriers that currently exist and impede the advance of new management methods. The purpose of this paper is to define and delimit problems to be solved so that it is possible to implement a new management model for a collaborative design process.