Partial protection against chlamydial reproductive tract infection by a recombinant major outer membrane protein/CpG/cholera toxin intranasal vaccine in the guinea pig Chlamydia cavaie model

Chlamydia trachomatis is a major cause of sexually transmitted diseases worldwide. There currently is no vaccine to protect against chlamydial infection of the female reproductive tract. Vaccine development has predominantly involved using the murine model, however infection of female guinea pigs with Chlamydia caviae more closely resembles chlamydial infection of the human female reproductive tract, and presents a better model to assess potential human chlamydial vaccines. We immunised female guinea pigs intranasally with recombinant major outer membrane protein (r-MOMP) combined with CpG-10109 and cholera toxin adjuvants. Both systemic and mucosal immune responses were elicited in immunised animals. MOMP-specific IgG and IgA were present in the vaginal mucosae, and high levels of MOMP-specific IgG were detected in the serum of immunised animals. Antibodies from the vaginal mucosae were also shown to be capable of neutralising C. caviae in vitro. Following immunisation, animals were challenged intravaginally with a live C. caviae infection of 102 inclusion forming units. We observed a decrease in duration of infection and a significant (p<0.025) reduction in infection load in r-MOMP immunised animals, compared to animals immunised with adjuvant only. Importantly, we also observed a marked reduction in upper reproductive tract (URT) pathology in r-MOMP immunised animals. Intranasal immunisation of female guinea pigs with r-MOMP was able to provide partial protection against C. caviae infection, not only by reducing chlamydial burden but also URT pathology. This data demonstrates the value of using the guinea pig model to evaluate potential chlamydial vaccines for protection against infection and disease pathology caused by C. trachomatis in the female reproductive tract.

A comparison of the effects of a chlamydial vaccine administered during or after a C. muridarum urogenital infection of female mice

There are approximately 92 million new chlamydial infections of the genital tract in humans diagnosed each year, costing health care systems billions of dollars in treatment not only of acute infections, but also of associated inflammatory sequelae, such as pelvic inflammatory disease (PID) and ectopic pregnancy. These numbers are increasing at a steady rate and, due to the asymptomatic nature of infections, the incidence may be underestimated and the costs of treatment therefore higher. Over the previous few decades there has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections. The majority of this research has focused on females, due to the high rate of development of associated diseases, including PID, which can lead to ectopic pregnancy and infertility. In light of the increasing infection rates that have occurred despite the availability of antibiotics, and the asymptomatic nature of chlamydial infections, it is imperative that an efficacious vaccine that protects against infection and associated pathology be developed.

Active transonic aerofoil design optimization using robust multiobjective evolutionary algorithms

The use of adaptive wing/aerofoil designs is being considered, as they are promising techniques in aeronautic/ aerospace since they can reduce aircraft emissions and improve aerodynamic performance of manned or unmanned aircraft. This paper investigates the robust design and optimization for one type of adaptive techniques: active flow control bump at transonic flow conditions on a natural laminar flow aerofoil. The concept of using shock control bump is to control supersonic flow on the suction/pressure side of natural laminar flow aerofoil that leads to delaying shock occurrence (weakening its strength) or boundary layer separation. Such an active flow control technique reduces total drag at transonic speeds due to reduction of wave drag. The location of boundary-layer transition can influence the position and structure of the supersonic shock on the suction/pressure side of aerofoil. The boundarylayer transition position is considered as an uncertainty design parameter in aerodynamic design due to the many factors, such as surface contamination or surface erosion. This paper studies the shock-control-bump shape design optimization using robust evolutionary algorithms with uncertainty in boundary-layer transition locations. The optimization method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing, and asynchronous evaluation. The use of adaptive wing/aerofoil designs is being considered, as they are promising techniques in aeronautic/ aerospace since they can reduce aircraft emissions and improve aerodynamic performance of manned or unmanned aircraft. This paper investigates the robust design and optimization for one type of adaptive techniques: active flow control bump at transonic flow conditions on a natural laminar flow aerofoil. The concept of using shock control bump is to control supersonic flow on the suction/pressure side of natural laminar flow aerofoil that leads to delaying shock occurrence (weakening its strength) or boundary-layer separation. Such an active flow control technique reduces total drag at transonic speeds due to reduction of wave drag. The location of boundary-layer transition can influence the position and structure of the supersonic shock on the suction/pressure side of aerofoil. The boundarylayer transition position is considered as an uncertainty design parameter in aerodynamic design due to the many factors, such as surface contamination or surface erosion. This paper studies the shock-control-bump shape design optimization using robust evolutionary algorithms with uncertainty in boundary-layer transition locations. The optimization method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing, and asynchronous evaluation. Two test cases are conducted: the first test assumes the boundary-layer transition position is at 45% of chord from the leading edge, and the second test considers robust design optimization for the shock control bump at the variability of boundary-layer transition positions. The numerical result shows that the optimization method coupled to uncertainty design techniques produces Pareto optimal shock-control-bump shapes, which have low sensitivity and high aerodynamic performance while having significant total drag reduction.

Effect of external high pressures on the clay mineral sodium montmorillonite intercalated with methylated octadecylammonium bromide surfactants

Raman microprobe spectra of the clay mineral Wyoming SWy-2-sodium montmorillonite intercalated with the surfactants, methyltrioctadecylammonium bromide (TOMA) dimethyldiotadecylammonium bromide (DODMA) and octadecyl-trimethylammonium bromide (ODTMA), have been measured in the CH2 stretching region at external pressures up to ~40 kbar with the aid of a diamond-anvil cell. In the case of the intercalated clays containing TOMA and DODMA, the Raman data afford evidence for gauche to trans conformational changes in the orientation of the CH2 chains in the surfactants with increasing pressure. These conformational changes are reversed completely upon the release of pressure.

Homodimerization controls the fibroblast growth factor 9 subfamily's receptor binding and heparan sulfate-dependent diffusion in the extracellular matrix

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human diseases, necessitating multiple layers of self-regulatory control mechanisms to keep its activity in check. Herein, we demonstrate that FGF9 and FGF20 ligands undergo a reversible homodimerization, occluding their key receptor binding sites. To test the role of dimerization in ligand autoinhibition, we introduced structure-based mutations into the dimer interfaces of FGF9 and FGF20. The mutations weakened the ability of the ligands to dimerize, effectively increasing the concentrations of monomeric ligands capable of binding and activating their cognate FGF receptor in vitro and in living cells. Interestingly, the monomeric ligands exhibit reduced heparin binding, resulting in their increased radii of heparan sulfate-dependent diffusion and biologic action, as evidenced by the wider dilation area of ex vivo lung cultures in response to implanted mutant FGF9-loaded beads. Hence, our data demonstrate that homodimerization autoregulates FGF9 and FGF20's receptor binding and concentration gradients in the extracellular matrix. Our study is the first to implicate ligand dimerization as an autoregulatory mechanism for growth factor bioactivity and sets the stage for engineering modified FGF9 subfamily ligands, with desired activity for use in both basic and translational research.

FGFR2 mutations are rare across histologic subtypes of ovarian cancer

OBJECTIVE: Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. METHODS: Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. RESULTS: FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. CONCLUSIONS: Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors.

Experimental and finite element analysis of a double strap joint between steel plates and normal modulus CFRP

Strengthening of steel structures using externally-bonded carbon fibre reinforced polymers ‘CFRP’ is a rapidly developing technique. This paper describes the behaviour of axially loaded flat steel plates strengthened using carbon fibre reinforced polymer sheets. Two steel plates were joined together with adhesive and followed by the application of carbon fibre sheet double strap joint with different bond lengths. The behaviour of the specimens was further investigated by using nonlinear finite element analysis to predict the failure modes and load capacity. In this study, bond failure is the dominant failure mode for normal modulus (240 GPa) CFRP bonding which closely matched the results of finite elements. The predicted ultimate loads from the FE analysis are found to be in good agreement with experimental values.

The beliefs which motivate young male and female drivers to speed : a comparison of low and high intenders

In Australia, young drivers aged 17 to 24 years, and particularly males, have the highest risk of being involved in a fatal crash. Investigation of young drivers’ beliefs allows for a greater understanding of their involvement in risky behaviours, such as speeding, as beliefs are associated with intentions, the antecedent to behaviour. The theory of planned behaviour (TPB) was used to conceptualise beliefs using a scenario based questionnaire distributed to licensed drivers (N = 398). The questionnaire measured individual’s beliefs and intentions to speed in a particular situation. Consistent with a TPB-based approach, the beliefs of those with low intentions to speed (‘low intenders’) were compared with the beliefs of those with high intentions (‘high intenders’) with such comparisons conducted separately for males and females. Overall, significant differences in the beliefs held by low and high intenders and for both females and males were found. Specifically, for females, it was found that high intenders were significantly more likely to perceive advantages of speeding, less likely to perceive disadvantages, and more likely to be encouraged to speed on familiar and inappropriately signed roads than female low intenders. Females, however, did not differ in their perceptions of support from friends, with all females reporting some level of disapproval from most friends and all females (i.e., low and high intenders) reporting approval to speed from their male friends. The results for males revealed that high intenders were significantly more likely to speed on familiar and inappropriately signed roads as well as having greater perceptions of support from all friends, except from those friends with whom they worked. Low and high intending males did not differ in their perceptions of the advantages and disadvantages of speeding, with the exception of feelings of excitement whereby high intenders reported speeding to be more exciting than low intenders. The findings are discussed in terms of how they may directly inform the content of mass media and public education campaigns aimed at encouraging young drivers to slow down.

Why adopt now? Multiple case studies and survey studies comparing small, medium and large firms

While a number of factors have been highlighted in the innovation adoption literature, little is known about whether different factors are related to innovation adoption in differently-sized firms. We used preliminary case studies of small, medium and large firms to ground our hypotheses, which were then tested using a survey of 94 firms. We found that external stakeholder pressure and non-financial readiness were related to innovation adoption in SMEs; but that for large firms, adoption was related to the opportunity to innovate. It may be that the difficulties of adopting innovations, including both the financial cost and the effort involved, are too great for SMEs to overcome unless there is either a compelling need (external pressure) or enough in-house capability (non-financial readiness). This suggests that SMEs are more likely to have innovation “pushed” onto them while large firms are more likely to “pull” innovations when they have the opportunity.

Quantification of the accuracy of MRI generated 3D models of long bones compared to CT generated 3D models

Orthopaedic fracture fixation implants are increasingly being designed using accurate 3D models of long bones based on computer tomography (CT). Unlike CT, magnetic resonance imaging (MRI) does not involve ionising radiation and is therefore a desirable alternative to CT. This study aims to quantify the accuracy of MRI-based 3D models compared to CT-based 3D models of long bones. The femora of five intact cadaver ovine limbs were scanned using a 1.5T MRI and a CT scanner. Image segmentation of CT and MRI data was performed using a multi-threshold segmentation method. Reference models were generated by digitising the bone surfaces free of soft tissue with a mechanical contact scanner. The MRI- and CT-derived models were validated against the reference models. The results demonstrated that the CT-based models contained an average error of 0.15mm while the MRI-based models contained an average error of 0.23mm. Statistical validation shows that there are no significant differences between 3D models based on CT and MRI data. These results indicate that the geometric accuracy of MRI based 3D models was comparable to that of CT-based models and therefore MRI is a potential alternative to CT for generation of 3D models with high geometric accuracy.

Targeting mutant fibroblast growth factor receptors in cancer

Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.

Quantifying in-plane deformation of plate elements using vibration characteristics

Plate elements are used in many engineering applications. In-plane loads and deformations have significant influence on the vibration characteristics of plate elements. Numerous methods have been developed to quantify the effects of in-plane loads and deformations of individual plate elements with different boundary conditions based on their natural frequencies. However, these developments cannot be applied to the plate elements in a structural system as the natural frequency is a global parameter for the entire structure. This highlights the need for a method to quantify in-plane deformations of plate elements in structural framing systems. Motivated by this gap in knowledge, this research has developed a comprehensive vibration based procedure to quantify in-plane deformation of plate elements in a structural framing system. This procedure with its unique capabilities to capture the influence of load migration, boundary conditions and different tributary areas is presented herein and illustrated through examples.

CAT Detect (Computer Activity Timeline Detection) : a tool for detecting inconsistency in computer activity timelines

The construction of timelines of computer activity is a part of many digital investigations. These timelines of events are composed of traces of historical activity drawn from system logs and potentially from evidence of events found in the computer file system. A potential problem with the use of such information is that some of it may be inconsistent and contradictory thus compromising its value. This work introduces a software tool (CAT Detect) for the detection of inconsistency within timelines of computer activity. We examine the impact of deliberate tampering through experiments conducted with our prototype software tool. Based on the results of these experiments, we discuss techniques which can be employed to deal with such temporal inconsistencies.

Contribution of take-out food consumption to socioeconomic differences in fruit and vegetable intake : a mediation analysis

Lower fruit and vegetable intake among socioeconomically disadvantaged groups has been well documented, and may be a consequence of a higher consumption of take-out foods. This study examined whether, and to what extent, take-out food consumption mediated (explained) the association between socioeconomic position and fruit and vegetable intake. A cross-sectional postal survey was conducted among 1500 randomly selected adults aged 25–64 years in Brisbane, Australia in 2009 (response rate = 63.7%, N = 903). A food frequency questionnaire assessed usual daily servings of fruits and vegetables (0 to 6), overall take-out consumption (times/week) and the consumption of 22 specific take-out items (never to ≥once/day). These specific take-out items were grouped into “less healthy” and “healthy” choices and indices were created for each type of choice (0 to 100). Socioeconomic position was ascertained by education. The analyses were performed using linear regression, and a bootstrap re-sampling approach estimated the statistical significance of the mediated effects. Mean daily serves of fruits and vegetables was 1.89 (SD 1.05) and 2.47 (SD 1.12) respectively. The least educated group were more likely to consume fewer serves of fruit (B= –0.39, p<0.001) and vegetables (B= –0.43, p<0.001) compared with the highest educated. The consumption of “less healthy” take-out food partly explained (mediated) education differences in fruit and vegetable intake; however, no mediating effects were observed for overall and “healthy” take-out consumption. Regular consumption of “less healthy” take-out items may contribute to socioeconomic differences in fruit and vegetable intake, possibly by displacing these foods.

A review of locative media, mobile and embodied spatial interaction

Highlights ► Provides a review of the history and development of locative media. ► Outlines different human-computer interaction techniques applied in locative media. ► Discusses how locative media applications have changed interaction affordances in and of physical spaces. ► Discusses practices of people in urban settings that evolved through these new affordances. ► Provides an overview on methods to investigate and elaborate design principles for future locative media.