A hepatitis C virus DNA vaccine encoding a secreted, oligomerized form of envelope proteins is highly immunogenic and elicits neutralizing antibodies in vaccinated mice

Hepatitis C virus (HCV) persistently infects approximately 71 million people globally. To prevent infection a vaccine which elicits neutralizing antibodies against the virus envelope proteins (E1/E2) which are required for entry into host cells is desirable. DNA vaccines are cost-effective to manufacture globally and despite recent landmark studies highlighting the therapeutic efficacy of DNA vaccines in humans against cervical cancer, DNA vaccines encoding E1/E2 developed thus far are poorly immunogenic. We now report a novel and highly immunogenic DNA vaccination strategy that incorporates secreted E1 and E2 (sE1 and sE2) into oligomers by fusion with the oligomerization domain of the C4b-binding protein, IMX313P. The FDA approved plasmid, pVax, was used to encode sE1, sE2, or sE1E2 with or without IMX313P, and intradermal prime-boost vaccination studies in BALB/c mice showed that vaccines encoding IMX313P were the most effective in eliciting humoral and cell-mediated immunity against the envelope proteins. Further boosting with recombinant E1E2 proteins but not DNA nor virus-like particles (VLPs) expressing E1E2 increased the immunogenicity of the DNA prime-boost regimen. Nevertheless, the antibodies generated by the homologous DNA prime-boost vaccinations more effectively inhibited the binding of VLPs to target cells and neutralized transduction with HCV pseudoparticles (HCVpp) derived from different genotypes including genotypes 1, 2, 3, 4, 5, and 6. This report provides the first evidence that IMX313P can be used as an adjuvant for E1/E2-based DNA vaccines and represents a translatable approach for the development of a HCV DNA vaccine.Makutiro Ghislain Masavuli, Danushka K. Wijesundara, Alexander Underwood, Dale Christiansen, Linda Earnest-Silveira, Rowena Bull, Joseph Torresi, Eric J. Gowans and Branka Grubor-Bau

The sensorium at work: the sensory phenomenology of the working body

The sociology of the body and the sociology of work and occupations have both neglected to some extent the study of the ‘working body’ in paid employment, particularly with regard to empirical research into the sensory aspects of working practices. This gap is perhaps surprising given how strongly the sensory dimension features in much of working life. This article is very much a first step in calling for a more phenomenological, embodied and ‘fleshy’ perspective on the body in employment, and examines some of the theoretical and conceptual resources available to researchers wishing to focus on the lived working-body experiences of the sensorium. We also consider some possible representational forms for a more evocative, phenomenologically-inspired portrayal of sensory, lived-working-body experiences, and offer suggestions for future avenues of research

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Verification of raker shores using New Zealand timber

This paper investigates the capacity of full triangle (fixed) raker shores using New Zealand Timber, through analytical analyses and experimental tests. Full triangle (fixed) raker shores, or simply raker shores, are a temporary structure used to support collapsed or damaged buildings. They are used extensively by Urban Search and Rescue (USAR) teams around the world to allow the safe location and rescue of victims of collapsed or damaged buildings following an earthquake event. The shores used by New Zealand USAR are similar to those used in the United States; however they are made from Radiata Pine which has different mechanical properties than the timber used in the U.S. Hence, the need to verify the shores constructed in New Zealand still provide the required design strength. The analytical verification suggests that raker shores are unsafe, according to the New Zealand Timber Structures Standard NZS 3603:1993. However, the experimental results on full-scale specimens indicate that the performance of the raker shores satisfies the required demands, with a safety factor of 2 with regard to the design load, and a ductile type of failure. Suggestions to increase the capacity of the shores are also included

Reviewing the uncertainties in seismic experimentation following the unexpected performance of RC structures in the 2010-2011 Canterbury earthquakes

The performance of conventionally designed reinforced concrete (RC) structures during the 2011 Christchurch earthquake has demonstrated that there is greater uncertainty in the seismic performance of RC components than previously understood. RC frame and wall structures in the Christchurch central business district were observed to form undesirable cracks patterns in the plastic hinge region while yield penetration either side of cracks, and into development zones, were less than theoretical predictions. The implications of this unexpected behaviour: (i) significantly less available ductility; (ii) less hysteretic energy dissipation; and (iii) the localization of peak reinforcement strains, results in considerable doubt for the residual capacity of RC structures. The significance of these consequences has prompted a review of potential sources of uncertainty in seismic experimentation with the intention to improve the current confidence level for newly designed conventional RC structures. This paper attempts to revisit the principles of RC mechanics, in particular, to consider the influence of loading history, concrete tensile strength, and reinforcement ratio on the performance of ‘real’ RC structures compared to experimental test specimens

Assessment of hollow-core floors for seismic performance

Research Report: 2010-02The objective in writing this report is to provide a guide to structural engineers on how to assess the potential seismic performance of existing hollow-core floors in buildings and the steps involved in the design of new floors. Hollow-core units in New Zealand do not contain stirrups within the precast concrete section. This is due to the way that they are manufactured. The only reinforcement in the great majority of hollow-core units consists of pretensioned strands that are located close to the soffit. A consequence of this is that hollow-core units have a number of potential brittle failure modes that can occur when adverse structural actions are induced in the units. These adverse actions can be induced in a major earthquake due to the relative vertical, horizontal and rotational displacements that occur between hollow-core units and adjacent structural elements, such as beams or structural walls. A number of large scale structural tests backed up by analytical research has shown that extensive interaction occurs between floors containing prestressed precast units and other structural elements, such as walls and beams. The constraint that prestressed units in a floor can apply to adjacent beams can result in an increase in strength of the beams to a considerably greater strength than that indicated in editions of the New Zealand Structural Concrete Standard published prior to 2006. The extent of this increase is such that it could in some cases result in the development of a non-ductile failure mechanism instead of the ductile failure mechanism assumed in the design. Prestressed floor units tie the floor bays together leaving a weak section where the floor joins to supporting structural elements. The restraint provided by the prestress restricts the opening of cracks within the bay. In the event of an earthquake this restraint can result in wide cracks developing at some of the boundaries to floor bays. These cracks may have a significant influence on the performance of the floor when it acts as a diaphragm to transfer seismic forces to the lateral force resisting structural elements in the building. The report contains details of; 1. The different failure modes, which may be induced in hollow-core floors, and the failure modes that may develop in a buildings due to the presence of hollow-core units in the floors; 2. Criteria that may be used to assess the magnitude of the design earthquake which may be safely resisted by a hollow-core floor in a building; 3. Details of how construction practice related to the use of hollow-core floors in New Zealand has changed over the last five decades. This highlights particular aspects that need to be considered in carrying out an assessment of existing hollow-core floors; 4. Information on how a new hollow-core floor may be designed to be consistent with the Earthquake Actions Standard, NZS1170.5: 2004 and the Structural Concrete Standard, NZS3101: 2006 (plus Amendment 2); 5. A review of the research findings relevant to the behaviour of New Zealand hollow-core floors under earthquake conditions. Research that was used to develop the assessment and design criteria is described together with details of how the different criteria were developed from this work

Seismic Performance of Hollow-core Flooring: the Significance of Negative Bending Moments

Hollow-core flooring units, as described in the technical literature, are intended to be used as simply supported members. However, in construction continuity is often established between the units and supporting structure by the addition of insitu topping concrete and reinforcement. This change in structural form can result in negative moments and axial forces being induced in the floor by gravity loads, wind and seismic actions. Vertical seismic ground motion in particular can make a significant contribution to negative moments induced in the floor. This paper focuses on two failure mechanisms which may occur in negative moment regions of hollow-core floors, namely a flexural failure and a shear failure. It is shown that, with the detailing in common use prior to the release of the Structural Concrete Standard, NZS 3101-2006, there is a potential for brittle negative moment failure to occur under seismic conditions. Analytical work indicates that under some conditions a diagonal tension (shear) failure may also occur. As the failure of a floor may lead to progressive collapse it is important that these two aspects are considered along with a number of other potential failure modes in the retrofit or design of buildings. Guidance is given on methods of assessing the negative moment flexural strength and shear strength of hollow-core floors

Experimental Investigation of Existing Hollowcore Seating Connection Seismic Behaviour Pre and Post Retrofit Intervention,

In the recent past a number of issues regarding the seismic performance of typical existing hollowcore floor systems have been raised. The most concerning of these is the vulnerability to loss of vertical support of the floor system at the end floor to seating beam connection. This vulnerability arises due to incompatibilities between the floor system and intrinsic deformations of the neighbouring seismic frames. In a previous contribution by the authors (Jensen et al 2006), a conceptual retrofit strategy for existing hollowcore seating connections was proposed. This paper provides an experimental validation of that strategy through quasi-static cyclic testing of alternative seating connection configurations, adopting varying seating lengths. In general, unfavourable performance was exhibited by the existing seating connections, resulting in loss of vertical support of the hollowcore unit. In contrast, when additional seating and selective weakening retrofit approaches were implemented, a higher level of seismic performance leading to collapse prevention was achieved. In conclusion, issues and uncertainties associated with the evaluation of the likely failure mechanism, as well as the definition of an appropriate retrofit intervention are discussed

Conceptual retrofit strategy for existing hollowcore seating connections

Previous research regarding the seismic performance of existing precast hollowcore floor and ductile lateral frame systems has highlighted several behavioural uncertainties. In particular poor seismic performance due to deformation incompatibilities between the floor diaphragm and frame seismic resisting system have become apparent. Significant rotation and displacement demand on the floor systems due to frame beam elongation, seating beam rotation, and longitudinal perimeter vertical displacement have been identified as the main sources of undesirable damage. As a result the structural integrity at hollowcore seating and perimeter connection interfaces can be jeopardised, potentially leading to a partial or even complete floor collapse. In this paper an overview of expected compatibility issues is given while providing suggestions for conceptual low-invasive retrofit strategies. Particular focus will be given to the experimental investigation on the vulnerability of and suggested retrofit solutions for hollow core-seating connections. The Quasi-static experimental testing procedure focusing on a series of as-built and retrofitted specimens, reproducing a hollowcore-toseating- beam connection with traditionally adopted details will be presented. Both seating rotation due to the imposed lateral drift and beam elongation effects are simulated in the applied testing set-up. Simplified analysis and modelling aspects regarding the connection behaviour are discussed; expected damage and performance criteria associated with the alternative existing or retrofit solution are also tentatively indicated