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.

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.

A diode for correction-less small field output factor measurements

Introduction Due to their high spatial resolution diodes are often used for small field relative output factor measurements. However, a field size specific correction factor [1] is required and corrects for diode detector over-response at small field sizes. A recent Monte Carlo based study has shown that it is possible to design a diode detector that produces measured relative output factors that are equivalent to those in water. This is accomplished by introducing an air gap at the upstream end of the diode [2]. The aim of this study was to physically construct this diode by placing an ‘air cap’ on the end of a commercially available diode (the PTW 60016 electron diode). The output factors subsequently measured with the new diode design were compared to current benchmark small field output factor measurements. Methods A water-tight ‘cap’ was constructed so that it could be placed over the upstream end of the diode. The cap was able to be offset from the end of the diode, thus creating an air gap. The air gap width was the same as the diode width (7 mm) and the thickness of the air gap could be varied. Output factor measurements were made using square field sizes of side length from 5 to 50 mm, using a 6 MV photon beam. The set of output factor measurements were repeated with the air gap thickness set to 0, 0.5, 1.0 and 1.5 mm. The optimal air gap thickness was found in a similar manner to that proposed by Charles et al. [2]. An IBA stereotactic field diode, corrected using Monte Carlo calculated kq,clin,kq,msr values [3] was used as the gold standard. Results The optimal air thickness required for the PTW 60016 electron diode was 1.0 mm. This was close to the Monte Carlo predicted value of 1.15 mm2. The sensitivity of the new diode design was independent of field size (kq,clin,kq,msr = 1.000 at all field sizes) to within 1 %. Discussion and conclusions The work of Charles et al. [2] has been proven experimentally. An existing commercial diode has been converted into a correction-less small field diode by the simple addition of an ‘air cap’. The method of applying a cap to create the new diode leads to the diode being dual purpose, as without the cap it is still an unmodified electron diode.

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.

Radiographer commenting of trauma radiographs : a survey of the benefits, barriers and enablers to participation in an Australian healthcare setting

Introduction Radiographer abnormality detection systems that highlight abnormalities on trauma radiographs (‘red dot’ system) have been operating for more than 30 years. Recently, a number of pitfalls have been identified. These limitations initiated the evolution of a radiographer commenting system, whereby a radiographer provides a brief description of abnormalities identified in emergency healthcare settings. This study investigated radiographers' participation in abnormality detection systems, their perceptions of benefits, barriers and enablers to radiographer commenting, and perceptions of potential radiographer image interpretation services for emergency settings. Methods A cross-sectional survey was implemented. Participants included radiographers from four metropolitan hospitals in Queensland, Australia. Conventional descriptive statistics, histograms and thematic analysis were undertaken. Results Seventy-three surveys were completed and included in the analysis (68% response rate); 30 (41%) of respondents reported participating in abnormality detection in 20% or less of examinations, and 26(36%) reported participating in 80% or more of examinations. Five overarching perceived benefits of radiographer commenting were identified: assisting multidisciplinary teams, patient care, radiographer ability, professional benefits and quality of imaging. Frequently reported perceived barriers included ‘difficulty accessing image interpretation education’, ‘lack of time’ and ‘low confidence in interpreting radiographs’. Perceived enablers included ‘access to image interpretation education’ and ‘support from radiologist colleagues’. Conclusions A range of factors are likely to contribute to the successful implementation of radiographer commenting in addition to abnormality detection in emergency settings. Effective image interpretation education amenable to completion by radiographers would likely prove valuable in preparing radiographers for participation in abnormality detection and commenting systems in emergency settings.

Chemotaxis and chemokinesis of human prostate tumor cell lines in response to human prostate stromal cell secretory proteins containing a nerve growth factor-like protein

The migration of three human prostate tumor epithelial cell lines (TSU-pr1, PC-3, DU-145) in response to secreted protein from a human prostate stromal cell line was investigated by using the modified blind-well Boyden chamber assay. Migrated cells were quantified by spectrophotometrically measuring the concentration of crystal violet stain extracted from their nuclei. Cell number was correlated linearly with the concentration of extracted crystal violet stain. All three tumor cell lines showed intrinsic migratory ability in the absence of chemoattractants, such that approximately 1-7% of plated cells migrated across the filter of the Boyden chambers during a 5-h incubation period. Prostate tumor cell migration was significantly enhanced (3-13-fold) in response to stromal cell secretory protein in a dose-dependent manner, whereas bovine serum albumin had no effect on stimulating tumor cell migration. Immunoprecipitation of the stromal cell secreted protein with a nerve growth factor antibody partially and significantly reduced its stimulatory activity for tumor cell migration. A Zigmond-Hirsch matrix assay of tumor cell migration in response to various concentration gradients of stromal cell secreted protein demonstrated both chemotaxis and chemokinesis by all three cell lines. These results are consistent with the stromal cell secretory protein stimulation of chemokinetic tumor cell migration through the capsule of the prostate. Outside of the prostate gland metastasis of tumor cells may occur by chemotaxis to preferential sites containing chemoattractants similar to or related to maintenance factors that can substitute for components of stromal cell secretory protein.

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.

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.