Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP) family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF)-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5 mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue. Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

β-Arrestin2 regulates RANKL and Ephrins gene expression in response to bone remodeling in mice

PTH-stimulated intracellular signaling is regulated by the cytoplasmic adaptor molecule barrestin. We reported that the response of cancellous bone to intermittent PTH is reduced in b-arrestin22/2 mice and suggested that b-arrestins could influence the bone mineral balance by controlling RANKL and osteoprotegerin (OPG) gene expression. Here, we study the role of b-arrestin2 on the in vitro development and activity of bone marrow (BM) osteoclasts (OCs) and Ephrins ligand (Efn), and receptor (Eph) mRNA levels in bone in response to PTH and the changes of bone microarchitecture in wildtype (WT) and barrestin2 2/2 mice in models of bone remodeling: a low calcium diet (LoCa) and ovariectomy (OVX). The number of PTH-stimulated OCs was higher in BM cultures from b-arrestin22/2 compared with WT, because of a higher RANKL/OPG mRNA and protein ratio, without directly influencing osteoclast activity. In vivo, high PTH levels induced by LoCa led to greater changes in TRACP5b levels in b-arrestin22/2 compared with WT. LoCa caused a loss of BMD and bone microarchitecture, which was most prominent in b-arrestin22/2. PTH downregulated Efn and Eph genes in b-arrestin22/2, but not WT. After OVX, vertebral trabecular bone volume fraction and trabecular number were lower in b-arrestin22/2 compared with WT. Histomorphometry showed that OC number was higher in OVX-b-arrestin22/2 compared with WT. These results indicate that b-arrestin2 inhibits osteoclastogenesis in vitro, which resulted in decreased bone resorption in vivo by regulating RANKL/OPG production and ephrins mRNAs. As such, b-arrestins should be considered an important mechanism for the control of bone remodeling in response to PTH and estrogen deprivation.

Antibodies mediate formation of neutrophil extracellular traps in the middle ear and facilitate secondary pneumococcal otitis media

Otitis media (OM) (a middle ear infection) is a common childhood illness that can leave some children with permanent hearing loss. OM can arise following infection with a variety of different pathogens, including a coinfection with influenza A virus (IAV) and Streptococcus pneumoniae (the pneumococcus). We and others have demonstrated that coinfection with IAV facilitates the replication of pneumococci in the middle ear. Specifically, we used a mouse model of OM to show that IAV facilitates the outgrowth of S. pneumoniae in the middle ear by inducing middle ear inflammation. Here, we seek to understand how the host inflammatory response facilitates bacterial outgrowth in the middle ear. Using B cell-deficient infant mice, we show that antibodies play a crucial role in facilitating pneumococcal replication. We subsequently show that this is due to antibody-dependent neutrophil extracellular trap (NET) formation in the middle ear, which, instead of clearing the infection, allows the bacteria to replicate. We further demonstrate the importance of these NETs as a potential therapeutic target through the transtympanic administration of a DNase, which effectively reduces the bacterial load in the middle ear. Taken together, these data provide novel insight into how pneumococci are able to replicate in the middle ear cavity and induce disease.

Groundwater table response to sea level rise and its impact on pavement structure

It has been predicted that sea level will rise about 0.8 m by 2100. Consequently, seawater can intrude into the coastal aquifers and change the level of groundwater table. A raise in groundwater table due to seawater intrusion threats the coastal infrastructure such as road pavements. The mechanical properties of subgrade materials will change due to elevated rise of groundwater table, leading to pavement weakening and decreasing the subgrade strength and stiffness. This paper presents an assessment of the vulnerability of subgrade in coastal areas to change in groundwater table due to sea-level rise. A simple bathtub approach is applied for estimating the groundwater level changes according to sea-level rise. Then the effect of groundwater level changes on the soil water content (SWC) of a single column of fine-sand soil is simulated using MIKE SHE. The impact of an increase in moisture content on subgrade strength/stiffness is assessed for a number of scenarios.

Blast response and vulnerability assessment of piled foundations

This research treated the response of pile foundations to blast loads. The influence of important parameters was investigated. The research techniques and the results will enable safer design of pile foundations that are vulnerable to blast loads.

Response variation of optically stimulated luminescence dosimeters

Introduction This study investigates uncertainties pertaining to the use of optically stimulated luminescence dosimeters (OSLDs) in radiotherapy dosimetry. The sensitivity of the luminescent material is related to the density of recombination centres [1], which is in the range of 1015–1016 cm-3. Because of this non-uniform distribution of traps in crystal growth the sensitivity varies substantially within a batch of dosimeters. However, a quantitative understanding of the relationship between the response of an OSLD and its sensitive volume has not yet been investigated or reported in literature. Methods In this work, OSLDs are scanned with a MicroCT scanner to determine potential sources for the variation in relative sensitivity across a selection of Landauer nanoDot dosimeters. Specifically, the correlation between a dosimeters relative sensitivity and the loading density of Al2O3:C powder was determined. Results When extrapolating the sensitive volume’s radiodensity from the CT data, it was shown that there is a non-uniform distribution incrystal growth as illustrated in Fig. 1. A plot of voxel count versus the element-specific correction factor is shown in Fig. 2 where each point represents a single OSLD. A line was fitted which has an R2-value of 0.69 and a P-value of 8.21 9 10-19. This data shows that the response of a dosimeter decreases proportionally with sensitive volume. Extrapolating from this data, a quantitative relationship between response and sensitive volume was roughly determined for this batch of dosimeters. A change in volume of 1.176 9 10-5 cm3 corresponds to a 1 % change in response. In other words, a 0.05 % change in the nominal volume of the chip would result in a 1 % change in response. Discussion and conclusions This work demonstrated that the amount of sensitive material is approximately linked to the total correction factor. Furthermore, the ‘true’ volume of an OSLD’s sensitive material is, on average, 17.90 % less than that which has been reported in literature, mainly due to the presence of air cavities in the material’s structure. Finally, the potential effects of the inaccuracy of Al2O3:C deposition increases with decreasing chip size. If a luminescent dosimeter were manufactured with a smaller volume than currently employed using the same manufacturing protocol, the variation in response from chip to chip would more than likely exceed the current 5 % range.

Studies on the in-plane shear response of confined masonry shear walls

The prime aim of this research project is to evaluate the performance of confined masonry walls under in-plane shear with a view to contributing to the national masonry design standard through a set of design clauses. This aim stems from the criticisms of the current provisions of the in-plane shear capacity equations in the Australian Masonry Standard AS3700 (2011) being highly non-conservative. This PhD thesis is an attempt to address this gap in the knowledge through systematic investigation of the key parameters that affects the in-plane shear strength of the masonry walls through laboratory experiments and extensive finite element analyses.

Developing a framework of effective prevention and response strategies in workplace sexual harassment

Sexual harassment remains a widespread workplace phenomenon, despite laws that proscribe it. Drawing initially on a typology from the violence prevention literature that conceptualizes prevention and response approaches according to when they occur, the paper synthesizes strategies identified in literature addressing workplace sexual harassment, as well as other workplace injustices or grievances. The paper utilizes this previous research to develop a framework of sexual harassment prevention strategies along two dimensions: functions and timing. The framework offers a research-informed set of organization-wide preventative and remedial approaches, a systemic approach to what is often seen as an individual problem, and a means to better focus interventions that are often disparate and unco-ordinated. The paper also highlights important areas for future research including a stronger focus on longer-term (tertiary) corrective actions.

Pressure state response-based method for evaluating social benefits from smart grid development

In this paper, the inherent mechanism of social benefits associated with smart grid development is examined based on the pressure state response (PSR) model from resource economics. The emerging types of technology brought up by smart grid development are regarded as pressures. The improvements of the performance and efficiency of power system operation, such as the enhanced capability of accommodating renewable energy generation, are regarded as states. The effects of smart grid development on society are regarded as responses. Then, a novel method for evaluating social benefits from smart grid development is presented. Finally, the social benefits from smart grid development in a province in northwest China are carried out by using the developed evaluation system, and reasonable evaluation results are attained.

Invasive activity and chemotactic response to growth factors by Kaposi's sarcoma cells

Kaposi's sarcoma (KS) is a relatively low grade neoplasm, classically occurring in the skin of elderly men. A more virulent and invasive form of Kaposi's sarcoma has been described in patients with acquired immune deficiency syndrome (AIDS). The origin and identification of the tumor cells in these lesions is controversial. Here we have studied the behavior of cells derived from KS lesions in an in vitro assay which measures the ability of cells to invade through a reconstituted basement membrane. In agreement with previous work, KS cells obtained under selective culture conditions were invasive showing activity comparable to that of malignant tumor cells. Normal fibroblasts, smooth muscle cells, and endothelial cells did not demonstrate invasive behavior under the same experimental conditions. To characterize further the nature of the KS cells we tested the chemotactic response of cells from the most invasive line to a variety of growth factors and compared their response to those of fibroblasts, smooth muscle, and endothelial cells. These studies suggest that normal cells respond to a unique repertoire of chemotactic factors. The chemotactic response of the KS cells most closely resembled that of smooth muscle cells and was quite distinct from endothelial cells. These results indicate that the KS-derived cultures contain invasive cells with a smooth muscle cell-like phenotype.

A transcriptomic analysis of striped catfish (Pangasianodon hypophthalmus) in response to salinity adaptation: De novo assembly, gene annotation and marker discovery

The striped catfish (Pangasianodon hypophthalmus) culture industry in the Mekong Delta in Vietnam has developed rapidly over the past decade. The culture industry now however, faces some significant challenges, especially related to climate change impacts notably from predicted extensive saltwater intrusion into many low topographical coastal provinces across the Mekong Delta. This problem highlights a need for development of culture stocks that can tolerate more saline culture environments as a response to expansion of saline water-intruded land. While a traditional artificial selection program can potentially address this need, understanding the genomic basis of salinity tolerance can assist development of more productive culture lines. The current study applied a transcriptomic approach using Ion PGM technology to generate expressed sequence tag (EST) resources from the intestine and swim bladder from striped catfish reared at a salinity level of 9 ppt which showed best growth performance. Total sequence data generated was 467.8 Mbp, consisting of 4,116,424 reads with an average length of 112 bp. De novo assembly was employed that generated 51,188 contigs, and allowed identification of 16,116 putative genes based on the GenBank non-redundant database. GO annotation, KEGG pathway mapping, and functional annotation of the EST sequences recovered with a wide diversity of biological functions and processes. In addition, more than 11,600 simple sequence repeats were also detected. This is the first comprehensive analysis of a striped catfish transcriptome, and provides a valuable genomic resource for future selective breeding programs and functional or evolutionary studies of genes that influence salinity tolerance in this important culture species.

Heregulin regulates the actin cytoskeleton and promotes invasive properties in breast cancer cell lines

The metastatic process requires changes in tumor cell adhesion properties, cell motility and remodeling of the extracellular matrix. The erbB2 proto-oncogene is overexpressed in approximately 30% of breast cancers and is a major prognostic parameter when present in invasive disease. A ligand for the erbB2 receptor has not yet been identified but it can be activated by heterodimerization with heregulin (HRG)-stimulated erbB3 and erbB4 receptors. The HRGs are a family of polypeptide growth factors that have been shown to play a role in embryogenesis, tumor formation, growth and differentiation of breast cancer cells. The erbB3 and erbB4 receptors are involved in transregulation of erbB2 signaling. The work presented here suggests biological roles for HRG including regulation of the actin cytoskeleton and induction of motility and invasion in breast cancer cells. HRG-expressing breast cancer cell lines are characterized by low erbB receptor levels and a high invasive and metastatic index, while those which overexpress erbB2 demonstrate minimal invasive potential in vitro and are non-tumorigenic in vivo. Treatment of the highly tumorigenic and metastatic HRG-expressing breast cancer cell line MDA-MB-231 with an HRG-neutralizing antibody significantly inhibited proliferation in culture and motility in the Boyden chamber assay. Addition of exogenous HRG to non-invasive erbB2 overexpressing cells (SKBr-3) at low concentrations induced formation of pseudopodia, enhanced phagocytic activity and increased chemomigration and invasion in the Boyden chamber assay. The specificity of the chemomigration response to HRG is demonstrated by inhibition with the anti-HRG neutralizing antibody. These results suggest that either HRG can act as an autocrine or paracrine ligand to promote the invasive behavior of breast cancer cells in vitro or thus may enhance the metastatic process in vivo.

Reactive stepping behaviour in response to forward loss of balance predicts future falls in community-dwelling older adults

Background: a fall occurs when an individual experiences a loss of balance from which they are unable to recover. Assessment of balance recovery ability in older adults may therefore help to identify individuals at risk of falls. The purpose of this 12-month prospective study was to assess whether the ability to recover from a forward loss of balance with a single step across a range of lean magnitudes was predictive of falls. Methods: two hundred and one community-dwelling older adults, aged 65–90 years, underwent baseline testing of sensorimotor function and balance recovery ability followed by 12-month prospective falls evaluation. Balance recovery ability was defined by whether participants required either single or multiple steps to recover from forward loss of balance from three lean magnitudes, as well as the maximum lean magnitude participants could recover from with a single step. Results: forty-four (22%) participants experienced one or more falls during the follow-up period. Maximal recoverable lean magnitude and use of multiple steps to recover at the 15% body weight (BW) and 25%BW lean magnitudes significantly predicted a future fall (odds ratios 1.08–1.26). The Physiological Profile Assessment, an established tool that assesses variety of sensori-motor aspects of falls risk, was also predictive of falls (Odds ratios 1.22 and 1.27, respectively), whereas age, sex, postural sway and timed up and go were not predictive. Conclusion: reactive stepping behaviour in response to forward loss of balance and physiological profile assessment are independent predictors of a future fall in community-dwelling older adults. Exercise interventions designed to improve reactive stepping behaviour may protect against future falls.

Security analysis of the non-aggressive challenge response of the DNP3 Protocol using a CPN Model

Distributed Network Protocol Version 3 (DNP3) is the de-facto communication protocol for power grids. Standard-based interoperability among devices has made the protocol useful to other infrastructures such as water, sewage, oil and gas. DNP3 is designed to facilitate interaction between master stations and outstations. In this paper, we apply a formal modelling methodology called Coloured Petri Nets (CPN) to create an executable model representation of DNP3 protocol. The model facilitates the analysis of the protocol to ensure that the protocol will behave as expected. Also, we illustrate how to verify and validate the behaviour of the protocol, using the CPN model and the corresponding state space tool to determine if there are insecure states. With this approach, we were able to identify a Denial of Service (DoS) attack against the DNP3 protocol.