The microRNA expression signature on modified titanium implant surfaces influences genetic mechanisms leading to osteogenic differentiation

Topographically and chemically modified titanium implants are recognized to have improved osteogenic properties; however, the molecular regulation of this process remains unknown. This study aimed to determine the microRNA profile and the potential regulation of osteogenic differentiation following early exposure of osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF-β/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca2+ (WNT5A, FZD6) pathways, as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that the modified titanium surfaces could induce the activation of TGF-β/BMP and non-canonical WNT/Ca2+ signaling genes. The expression pattern of microRNAs (miRNAs) related to cell differentiation was evaluated. Statistical analysis of the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down-regulated on the modSLA and SLA surfaces respectively, when compared with the smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA surfaces, amongst which eight were the same as observed on modSLA. TargetScan predictions for the down-regulated miRNAs revealed genes of the TGF-β/BMP and non-canonical Ca2+ pathways as targets. This study demonstrated that modified titanium implant surfaces induce differential regulation of miRNAs, which potentially regulate the TGF-β/BMP and WNT/Ca2+ pathways during osteogenic differentiation on modified titanium implant surfaces.

The role of organisational culture, trust and mechanisms in inter-project knowledge sharing

Knowledge has been recognised as a powerful yet intangible asset, which is difficult to manage. This is especially true in a project environment where there is the potential to repeat mistakes, rather than learn from previous experiences. The literature in the project management field has recognised the importance of knowledge sharing (KS) within and between projects. However, studies in that field focus primarily on KS mechanisms including lessons learned (LL) and post project reviews as the source of knowledge for future projects, and only some preliminary research has been carried out on the aspects of project management offices (PMOs) and organisational culture (OC) in KS. This study undertook to investigate KS behaviours in an inter-project context, with a particular emphasis on the role of trust, OC and a range of knowledge sharing mechanisms (KSM) in achieving successful inter-project knowledge sharing (I-PKS). An extensive literature search resulted in the development of an I-PKS Framework, which defined the scope of the research and shaped its initial design. The literature review indicated that existing research relating to the three factors of OC, trust and KSM remains inadequate in its ability to fully explain the role of these contextual factors. In particular, the literature review identified these areas of interest: (1) the conflicting answers to some of the major questions related to KSM, (2) the limited empirical research on the role of different trust dimensions, (3) limited empirical evidence of the role of OC in KS, and (4) the insufficient research on KS in an inter-project context. The resulting Framework comprised the three main factors including: OC, trust and KSM, demonstrating a more integrated view of KS in the inter-project context. Accordingly, the aim of this research was to examine the relationships between these three factors and KS by investigating behaviours related to KS from the project managers‘ (PMs‘) perspective. In order to achieve the aim, this research sought to answer the following research questions: 1. How does organisational culture influence inter-project knowledge sharing? 2. How does the existence of three forms of trust — (i) ability, (ii) benevolence and (iii) integrity — influence inter-project knowledge sharing? 3. How can different knowledge sharing mechanisms (relational, project management tools and process, and technology) improve inter-project knowledge sharing behaviours? 4. How do the relationships between these three factors of organisational culture, trust and knowledge sharing mechanisms improve inter-project knowledge sharing? a. What are the relationships between the factors? b. What is the best fit for given cases to ensure more effective inter-project knowledge sharing? Using multiple case studies, this research was designed to build propositions emerging from cross-case data analysis. The four cases were chosen on the basis of theoretical sampling. All cases were large project-based organisations (PBOs), with a strong matrix-type structure, as per the typology proposed by the Project Management Body of Knowledge (PMBoK) (2008). Data were collected from project management departments of the respective organisations. A range of analytical techniques were used to deal with the data including pattern matching logic and explanation building analysis, complemented by the use of NVivo for data coding and management. Propositions generated at the end of the analyses were further compared with the extant literature, and practical implications based on the data and literature were suggested in order to improve I-PKS. Findings from this research conclude that OC, trust, and KSM contribute to inter-project knowledge sharing, and suggest the existence of relationships between these factors. In view of that, this research identified the relationships between different trust dimensions, suggesting that integrity trust reinforces the relationship between ability trust and knowledge sharing. Furthermore, this research demonstrated that characteristics of culture and trust interact to reinforce preferences for mechanisms of knowledge sharing. This means that cultures that facilitate characteristics of Clan type are more likely to result in trusting relationships, hence are more likely to use organic sources of knowledge for both tacit and explicit knowledge exchange. In contrast, cultures that are empirically driven, based on control, efficiency, and measures (characteristics of Hierarchy and Market types) display tendency to develop trust primarily in ability of non-organic sources, and therefore use these sources to share mainly explicit knowledge. This thesis contributes to the project management literature by providing a more integrative view of I-PKS, bringing the factors of OC, trust and KSM into the picture. A further contribution is related to the use of collaborative tools as a substitute for static LL databases and as a facilitator for tacit KS between geographically dispersed projects. This research adds to the literature on OC by providing rich empirical evidence of the relationships between OC and the willingness to share knowledge, and by providing empirical evidence that OC has an effect on trust; in doing so this research extends the theoretical propositions outlined by previous research. This study also extends the research on trust by identifying the relationships between different trust dimensions, suggesting that integrity trust reinforces the relationship between ability trust and KS. Finally, this research provides some directions for future studies.

Empirical analysis on relationship between traffic conditions and crash occurrences

This paper investigates relationship between traffic conditions and the crash occurrence likelihood (COL) using the I-880 data. To remedy the data limitations and the methodological shortcomings suffered by previous studies, a multiresolution data processing method is proposed and implemented, upon which binary logistic models were developed. The major findings of this paper are: 1) traffic conditions have significant impacts on COL at the study site; Specifically, COL in a congested (transitioning) traffic flow is about 6 (1.6) times of that in a free flow condition; 2)Speed variance alone is not sufficient to capture traffic dynamics’ impact on COL; a traffic chaos indicator that integrates speed, speed variance, and flow is proposed and shows a promising performance; 3) Models based on aggregated data shall be interpreted with caution. Generally, conclusions obtained from such models shall not be generalized to individual vehicles (drivers) without further evidences using high-resolution data and it is dubious to either claim or disclaim speed kills based on aggregated data.

Investigating the change in three dimensional deformity for idiopathic scoliosis using axially loaded MRI

Background: Adolescent idiopathic scoliosis is a complex three-dimensional deformity, involving a lateral deformity in the coronal plane and axial rotation of the vertebrae in the transverse plane. Gravitational loading plays an important biomechanical role in governing the coronal deformity, however, less is known about how they influence the axial deformity. This study investigates the change in three-dimensional deformity of a series of scoliosis patients due to compressive axial loading. Methods: Magnetic resonance imaging scans were obtained and coronal deformity (measured using the coronal Cobb angle) and axial rotations measured for a group of 18 scoliosis patients (Mean major Cobb angle was 43.4 o). Each patient was scanned in an unloaded and loaded condition while compressive loads equivalent to 50% body mass were applied using a custom developed compressive device. Findings: The mean increase in major Cobb angle due to compressive loading was 7.4 o (SD 3.5 o). The most axially rotated vertebra was observed at the apex of the structural curve and the largest average intravertebral rotations were observed toward the limits of the coronal deformity. A level-wise comparison showed no significant difference between the average loaded and unloaded vertebral axial rotations (intra-observer error = 2.56 o) or intravertebral rotations at each spinal level. Interpretation: This study suggests that the biomechanical effects of axial loading primarily influence the coronal deformity, with no significant change in vertebral axial rotation or intravertebral rotation observed between the unloaded and loaded condition. However, the magnitude of changes in vertebral rotation with compressive loading may have been too small to detect given the resolution of the current technique.

Resolution of the chiral (1R,2S) enantiomer of cis-cyclohexane-1,2-dicarboxylic acid in the brucinium salt 2,3-dimethoxy-10-oxostrychnidinium (1R,2S)-2-carboxycyclohexane-1-carboxylate dihydrate

The structure of the 1:1 brucinium salt of cis-cyclohexane-1,2-dicarboxylic acid, 2,3-dimethoxy-10-oxostrychnidinium (1R,2S)-2-carboxycyclohexane-1-carboxylate dihydrate, has revealed the resolved (1R,2S) enantiomer of the acid. Crystals of the compound are orthorhombic, space group P212121, with unit cell dimensions a = 8.1955(3), b = 12.4034(3), c = 29.9073(9)Å, and Z = 4. The asymmetric unit comprises the brucinium cation, the hydrogen cis-cyclohexane-1,2-dicarboxylate cation, in which the carboxylate group is disordered over two sites (58, 42%), and two water molecules of solvation, one of which is occupies two 50% occupancy sites. The classic undulating brucinium cation substructures are present with the anion and the water molecules occupying the interstitial cavities and are hydrogen-bonded to them in a two-dimensional network structure.

The Neighbourhood Disputes Resolution Act 2011 (Qld) and disclosure issues

This article examines the recently introduced Neighbourhood Disputes Resolution Act 2011 (Qld). The operation of the Act is considered as it impacts upon the responsibility of neighbours for dividing fences and trees as well as disclosure obligations associated with sale transactions. A particular focus of the article is the interrelationship of the disclosure obligations imposed by the Act with the operation of standard contractual warranties in Queensland.

Statistical analysis of conflict involvements in port water navigation

With increasing rate of shipping traffic, the risk of collisions in busy and congested port waters is likely to rise. However, due to low collision frequencies in port waters, it is difficult to analyze such risk in a sound statistical manner. A convenient approach of investigating navigational collision risk is the application of the traffic conflict techniques, which have potential to overcome the difficulty of obtaining statistical soundness. This study aims at examining port water conflicts in order to understand the characteristics of collision risk with regard to vessels involved, conflict locations, traffic and kinematic conditions. A hierarchical binomial logit model, which considers the potential correlations between observation-units, i.e., vessels, involved in the same conflicts, is employed to evaluate the association of explanatory variables with conflict severity levels. Results show higher likelihood of serious conflicts for vessels of small gross tonnage or small overall length. The probability of serious conflict also increases at locations where vessels have more varied headings, such as traffic intersections and anchorages; becoming more critical at night time. Findings from this research should assist both navigators operating in port waters as well as port authorities overseeing navigational management.

IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms

Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4+ and CD8+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1−/− mice or in mice depleted of CD4+ and/or CD8+ cells than in normal mice. The tumors in RAG1−/− mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

Preliminary validation of a novel high-resolution melt-based typing method based on the multilocus sequence typing scheme of Streptococcus pyogenes

The major limitation of current typing methods for Streptococcus pyogenes, such as emm sequence typing and T typing, is that these are based on regions subject to considerable selective pressure. Multilocus sequence typing (MLST) is a better indicator of the genetic backbone of a strain but is not widely used due to high costs. The objective of this study was to develop a robust and cost-effective alternative to S. pyogenes MLST. A 10-member single nucleotide polymorphism (SNP) set that provides a Simpson’s Index of Diversity (D) of 0.99 with respect to the S. pyogenes MLST database was derived. A typing format involving high-resolution melting (HRM) analysis of small fragments nucleated by each of the resolution-optimized SNPs was developed. The fragments were 59–119 bp in size and, based on differences in G+C content, were predicted to generate three to six resolvable HRM curves. The combination of curves across each of the 10 fragments can be used to generate a melt type (MelT) for each sequence type (ST). The 525 STs currently in the S. pyogenes MLST database are predicted to resolve into 298 distinct MelTs and the method is calculated to provide a D of 0.996 against the MLST database. The MelTs are concordant with the S. pyogenes population structure. To validate the method we examined clinical isolates of S. pyogenes of 70 STs. Curves were generated as predicted by G+C content discriminating the 70 STs into 65 distinct MelTs.