Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Scaling analysis of natural convection boundary layers : Application to attic space

The natural convection thermal boundary layer adjacent to an inclined flat plate and inclined walls of an attic space subject to instantaneous and ramp heating and cooling is investigated. A scaling analysis has been performed to describe the flow behaviour and heat transfer. Major scales quantifying the flow velocity, flow development time, heat transfer and the thermal and viscous boundary layer thicknesses at different stages of the flow development are established. Scaling relations of heating-up and cooling-down times and heat transfer rates have also been reported for the case of attic space. The scaling relations have been verified by numerical simulations over a wide range of parameters. Further, a periodic temperature boundary condition is also considered to show the flow features in the attic space over diurnal cycles.

The development of a conceptual framework for a district 4-Year Pavement Management Plan, implementation of network-level project screening process

The Texas Department of Transportation (TxDOT) is concerned about the widening gap between preservation needs and available funding. Funding levels are not adequate to meet the preservation needs of the roadway network; therefore projects listed in the 4-Year Pavement Management Plan must be ranked to determine which projects should be funded now and which can be postponed until a later year. Currently, each district uses locally developed methods to prioritize projects. These ranking methods have relied on less formal qualitative assessments based on engineers’ subjective judgment. It is important for TxDOT to have a 4-Year Pavement Management Plan that uses a transparent, rational project ranking process. The objective of this study is to develop a conceptual framework that describes the development of the 4-Year Pavement Management Plan. It can be largely divided into three Steps; 1) Network-Level project screening process, 2) Project-Level project ranking process, and 3) Economic Analysis. A rational pavement management procedure and a project ranking method accepted by districts and the TxDOT administration will maximize efficiency in budget allocations and will potentially help improve pavement condition. As a part of the implementation of the 4-Year Pavement Management Plan, the Network-Level Project Screening (NLPS) tool including the candidate project identification algorithm and the preliminary project ranking matrix was developed. The NLPS has been used by the Austin District Pavement Engineer (DPE) to evaluate PMIS (Pavement Management Information System) data and to prepare a preliminary list of candidate projects for further evaluation.

Investing in the future : analysis of TxDOT 1547 Over-Axle Weight Tolerance Permits

The trucking industry has played a significant role in the economic growth in Texas by transporting and distributing commodities using commercial motor vehicles. The Texas Department of Transportation (TxDOT), however, has recognized that the large number of overweight trucks operating on the state highway system has resulted in the deterioration of pavement condition. In addition, the permit fee to carry higher loads above legal limits is much lower than the cost to treat the increase in pavement damage. The primary purpose of the research presented in this paper is to investigate current TxDOT overweight permit structures to support pavement management. The research team analyzed the TxDOT “1547” Over-axle Weight Tolerance Permit structure to support an increase in the fee structure, bringing it more in line with the actual pavement damage. The analysis showed that the revised overweight permit structure could provide an additional $9.3 million annually for pavement maintenance needs by increasing current permit fees. These results were supported by the 2030 Committee for recommendation to the Texas Transportation Commission and consideration by the State Legislature [1]. The research team recommends conducting further research to identify methods for working cooperatively with the trucking industry to develop improved methods for assessing weight damage relationships and developing more effective and accurate means for assessing overweight permit fees.

Peer state assessment of TxDOT maintenance program and practices, part I : workshop findings and recommendations

To assess and improve their practices, and thus ensure the future excellence of the Texas highway system, the Texas Department of Transportation (TxDOT) sought a forum in which experts from other State Departments of Transportation could evaluate the TxDOT maintenance program and practices based on their expertise. To meet this need, a Peer State Review of TxDOT Maintenance Practices project was organized and conducted by the Center for Transportation Research (CTR) at The University of Texas at Austin. CTR researchers, along with TxDOT staff, conducted a workshop to present TxDOT’s maintenance practices to the visiting peer reviewers and invite their feedback. Directors of maintenance from six different states—California, Kansas, Georgia, Missouri, North Carolina, and Washington—participated in the workshop. CTR and TxDOT worked together to design a questionnaire with 15 key questions to capture the peers’ opinions on maintenance program and practices. This paper compiles and summarizes this information. The examination results suggested that TxDOT should use a more state-wide approach to funding and planning, in addition to funding and planning for each district separately. Additionally, the peers recommended that criteria such as condition and level of service of the roadways be given greater weight in the funding allocation than lane miles or vehicle miles traveled (VMT). The Peer Reviewers also determined that TxDOT maintenance employee experience and communications were strong assets. Additional strengths included the willingness of TxDOT to invite peer reviews of their practices and a willingness to consider opportunities for improvement.

Book review: Ford, R.C., & Peeper, W.C. 2008. Managing Destination Marketing Organizations. Orlando: ForPer Publications

This volume represents the proceedings of the 13th ENTER conference, held at Lausanne, Switzerland during 2006. The conference brought together academics and practitioners across four tracks, which were eSolutions, refereed research papers, work-in-progress papers, and a Ph.D. workshop. This proceedings contains 40 refereed papers, which is less than the 51 papers presented in 2005. However, the editors advise that the scientific committee was stricter than in previous years, to the extent that the acceptance rate was 50%. A significant change in the current proceedings is the inclusion of extended abstracts of the 23 work-in-progress presentations. The papers cover a diverse range of topics across 16 research streams. This reviewer has adopted the approach of succinctly summarising the contribution of each of the 40-refereed papers, in the order in which they appear...

Influence of field size on pupil diameter under photopic and mesopic light levels

Purpose: We investigated the interaction between adapting field size and luminance on pupil diameter when cones alone (photopic) or rods and cones (mesopic) were active. Method: Circular achromatic targets (1o to 24o diameter) were presented to eight young participants on a rectangular projector screen. The accommodative influence on pupil diameter was minimized using cycloplegia in the fixing right eye and the consensual pupil reflex was measured in the left eye. Target luminance was adjusted for each stimulus such that corneal flux density (product of field area and luminance) was constant at 3600 cd.deg2m-2 (photopic condition) and 1.49 cd.deg2m-2 (mesopic condition). Results: There were no statistically significant effects of adaptive field size on pupil diameter for either condition. Conclusion: If corneal flux density is kept constant, there will be no change in pupil diameter as the size of the stimulus field increases at either mesopic or photopic lighting levels up to at least 24°.

Commentaries and Responses to "The Driver Behaviour Questionnaire as a predictor of accidents: A meta-analysis" [Commentaries lead by Anders af Wahlberg; Responses lead by J.C.F. de Winter]

The following discussion is in response to a 2010 article published in the Journal of Safety Research by J.C.F. de Winter and D. Dodou entitled “The Driver Behaviour Questionnaire as a predictor of accidents: A meta-analysis” (Volume 41, Number 6, pp. 463-470, available on sciencedirect.com). The editors are pleased to provide a forum for this exchange and welcome further comments.

Effects of whole-body cryotherapy (-110 degrees C) on proprioception and indices of muscle damage

The purpose of this study was to investigate the effects of whole-body cryotherapy (WBC) on proprioceptive function, muscle force recovery following eccentric muscle contractions and tympanic temperature (TTY). Thirty-six subjects were randomly assigned to a group receiving two 3-min treatments of −110 ± 3 °C or 15 ± 3 °C. Knee joint position sense (JPS), maximal voluntary isometric contraction (MVIC) of the knee extensors, force proprioception and TTY were recorded before, immediately after the exposure and again 15 min later. A convenience sample of 18 subjects also underwent an eccentric exercise protocol on their contralateral left leg 24 h before exposure. MVIC (left knee), peak power output (PPO) during a repeated sprint on a cycle ergometer and muscles soreness were measured pre-, 24, 48 and 72 h post-treatment. WBC reduced TTY, by 0.3 °C, when compared with the control group (P<0.001). However, JPS, MVIC or force proprioception was not affected. Similarly, WBC did not effect MVIC, PPO or muscle soreness following eccentric exercise. WBC, administered 24 h after eccentric exercise, is ineffective in alleviating muscle soreness or enhancing muscle force recovery. The results of this study also indicate no increased risk of proprioceptive-related injury following WBC.

Functional and advanced functional and causal relationship diagrams for remote condition monitoring

Analysing the condition of an asset is a big challenge as there can be many aspects which can contribute to the overall functional reliability of the asset that have to be considered. In this paper we propose a two-step functional and causal relationship diagram (FCRD) to address this problem. In the first step, the FCRD is designed to facilitate the analysis of the condition of an asset by evaluating the interdependence (functional and causal) relationships between different components of the asset with the help of a relationship diagram. This is followed by the advanced FCRD (AFCRD) which refines the information from the FCRD into a comprehensive and manageable format. This new two-step methodology for asset condition monitoring is tested and validated for the case of a water treatment plant. © IMechE 2012.

The macrophage-inducible C-type lectin, Mincle, is an essential component of the innate immune response to Candida albicans

The recognition of carbohydrate moieties by cells of the innate immune system is emerging as an essential element in antifungal immunity, but despite the number and diversity of lectins expressed by innate immune cells, few carbohydrate receptors have been characterized. Mincle, a C-type lectin, is expressed predominantly on macrophages, and is here shown to play a role in macrophage responses to the yeast Candida albicans. After exposure to the yeast in vitro, Mincle localized to the phagocytic cup, but it was not essential for phagocytosis. In the absence of Mincle, production of TNF-_ by macrophages was reduced, both in vivo and in vitro. In addition, mice lacking Mincle showed a significantly increased susceptibility to systemic candidiasis. Thus, Mincle plays a novel and nonredundant role in the induction of inflammatory signaling in response to C. albicans infection.

Review ["Telling the Evolutionary Time : Molecular Clocks and the Fossil Record" edited by Philip C. J. Donoghue and M. Paul Smith]

Determining the temporal scale of biological evolution has traditionally been the preserve of paleontology, with the timing of species originations and major diversifications all being read from the fossil record. However, the ages of the earliest (correctly identified) records will underestimate actual origins due to the incomplete nature of the fossil record and the necessity for lineages to have evolved sufficiently divergent morphologies in order to be distinguished. The possibility of inferring divergence times more accurately has been promoted by the idea that the accumulation of genetic change between modern lineages can be used as a molecular clock (Zuckerkandl and Pauling, 1965). In practice, though, molecular dates have often been so old as to be incongruent even with liberal readings of the fossil record. Prominent examples include inferred diversifications of metazoan phyla hundreds of millions of years before their Cambrian fossil record appearances (e.g., Nei et al., 2001) and a basal split between modern birds (Neoaves) that is almost double the age of their earliest recognizable fossils (e.g., Cooper and Penny, 1997).

Australian children with special health care needs: Social-emotional and learning competencies in the early years

This study examined the relationship between special health care needs and social-emotional and learning competence in the early years, reporting on two waves of data from the Kindergarten Cohort of Growing up in Australia: The Longitudinal Study of Australian Children (LSAC). Six hundred and fifty children were identified through the 2-question Special Health Care Needs Screener as having special health care needs. Children with special health care needs were more likely to be male, to have been of low birth weight, to be taking prescription medications, to be diagnosed with a specific health condition and to be from families where the mother was less well educated. These children scored significantly lower on teacher-rated social-emotional and learning competencies prior to school compared to a control group of children without special health care needs. Multiple regression analyses indicated that being identified with a special health care need prior to school predicted lower social-emotional and learning competencies in the early years of school. Results are discussed in terms of the implications for policy and practice.

Diesel knock combustion and its detection using acoustic emission

This paper presents an experimental investigation into the detection of excessive Diesel knock using acoustic emission signals. Three different dual-fuel Diesel engine operating regimes were induced into a compression ignition (Diesel) engine operating on both straight Diesel fuel and two different mixtures of fumigated ethanol and Diesel. The experimentally induced engine operating regimes were; normal, or Diesel only operation, acceptable dual-fuel operation and dual-fuel operation with excessive Diesel knock. During the excessive Diesel knock operating regime, high rates of ethanol substitution induced potentially damaging levels of Diesel knock. Acoustic emission data was captured along with cylinder pressure, crank-angle encoder, and top-dead centre signals for the different engine operating regimes. Using these signals, it was found that acoustic emission signals clearly distinguished between the two acceptable operating regimes and the operating regime experiencing excessive Diesel knock. It was also found that acoustic emission sensor position is critical. The acoustic emission sensor positioned on the block of the engine clearly related information concerning the level of Diesel knock occurring in the engine whist the sensor positioned on the head of the engine gave no indication concerning Diesel knock severity levels.