Assessment of flood-related recharge to alluvial aquifers of an irrigated catchment following extended drought conditions using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia.

The Lockyer Valley in southeast Queensland, Australia, hosts an economically significant alluvial aquifer system which has been impacted by prolonged drought conditions (~1997 to ~ 2009). Throughout this time, the system was under continued groundwater extraction, resulting in severe aquifer depletion. By 2008, much of the aquifer was at <30% of storage but some relief occurred with rains in early 2009. However, between December 2010 and January 2011, most of southeast Queensland experienced unprecedented flooding, which generated significant aquifer recharge. In order to understand the spatial and temporal controls of groundwater recharge in the alluvium, a detailed 3D lithological property model of gravels, sands and clays was developed using GOCAD software. The spatial distribution of recharge throughout the catchment was assessed using hydrograph data from about 400 groundwater observation wells screened at the base of the alluvium. Water levels from these bores were integrated into a catchment-wide 3D geological model using the 3D geological modelling software GOCAD; the model highlights the complexity of recharge mechanisms. To support this analysis, groundwater tracers (e.g. major and minor ions, stable isotopes, 3H and 14C) were used as independent verification. The use of these complementary methods has allowed the identification of zones where alluvial recharge primarily occurs from stream water during episodic flood events. However, the study also demonstrates that in some sections of the alluvium, rainfall recharge and discharge from the underlying basement into the alluvium are the primary recharge mechanisms of the alluvium. This is indicated by the absence of any response to the flood, as well as the observed old radiocarbon ages and distinct basement water chemistry signatures at these locations. Within the 3D geological model, integration of water chemistry and time-series displays of water level surfaces before and after the flood suggests that the spatial variations of the flood response in the alluvium are primarily controlled by the valley morphology and lithological variations within the alluvium. The integration of time-series of groundwater level surfaces in the 3D geological model also enables the quantification of the volumetric change of groundwater stored in the unconfined sections of this alluvial aquifer during drought and following flood events. The 3D representation and analysis of hydraulic and recharge information has considerable advantages over the traditional 2D approach. For example, while many studies focus on singular aspects of catchment dynamics and groundwater-surface water interactions, the 3D approach is capable of integrating multiple types of information (topography, geological, hydraulic, water chemistry and spatial) into a single representation which provides valuable insights into the major factors controlling aquifer processes.

Assessment of interactions between alluvial, Great Artesian Basin (GAB) and volcanic aquifers using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia

A detailed 3D lithological model framework was developed using GOCAD software to understand interactions between alluvial, volcanic and GAB aquifers and the spatial and temporal distribution of groundwater recharge to the alluvium of the Lockyer Valley. Groundwater chemistry, isotope data (H20-δ2H and δ18O , 87Sr/86Sr, 3H and 14C) and groundwater level time-series data from approximately 550 observation wells were integrated into the catchment-wide 3D model to assess the recharge processes involved. This approach enabled the identification of zones where recharge to the alluvium primarily occurs from stream water during episodic flood events. Importantly, the study also demonstrates that in some sections of the alluvium recharge is also from storm rainfall and seepage discharge from the underlying GAB aquifers. These other sources of recharge are indicated by (a) the absence of a response of groundwater levels to flooding in some areas, (b) old radiocarbon ages, and (c) distinct bedrock water chemistry and δ2H and δ18O signatures in alluvial groundwater at these locations. Integration of isotopes, water chemistry and time-series displays of groundwater levels before and after the 2010/2011 flood into the 3D model suggest that the spatial variations in the alluvial groundwater response are mostly controlled by valley morphology and lithological (i.e. permeability) variations within the alluvium. Examination of the groundwater level variations in the 3D model also enabled quantification of the volumetric change of groundwater stored in the unconfined alluvial aquifer prior to and post-flood events.

Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Determination of coastal ground and surface water processes and character by use of hydrochemistry and stable isotopes, Fraser Coast, Queensland

This study was part of an integrated project developed in response to concerns regarding current and future land practices affecting water quality within coastal catchments and adjacent marine environments. Two forested coastal catchments on the Fraser Coast, Australia, were chosen as examples of low-modification areas with similar geomorphological and land-use characteristics to many other coastal zones in southeast Queensland. For this component of the overall project, organic , physico-chemical (Eh, pH and DO), ionic (Fe2+, Fe3+), and isotopic (ä13CDIC, ä15NDIN ä34SSO4) data were used to characterise waters and identify sources and processes contributing to concentrations and form of dissolved Fe, C, N and S within the ground and surface waters of these coastal catchments. Three sites with elevated Fe concentrations are discussed in detail. These included a shallow pool with intermittent interaction with the surface water drainage system, a monitoring well within a semi-confined alluvial aquifer, and a monitoring well within the fresh/saline water mixing zone adjacent to an estuary. Conceptual models of processes occurring in these environments are presented. The primary factors influencing Fe transport were; microbial reduction of Fe3+ oxyhydroxides in groundwaters and in the hyporheic zone of surface drainage systems, organic input available for microbial reduction and Fe3+ complexation, bacterial activity for reduction and oxidation, iron curtain effects where saline/fresh water mixing occurs, and variation in redox conditions with depth in ground and surface water columns. Data indicated that groundwater seepage appears a more likely source of Fe to coastal waters (during periods of low rainfall) via tidal flux. The drainage system is ephemeral and contributes little discharge to marine waters. However, data collected during a high rainfall event indicated considerable Fe loads can be transported to the estuary mouth from the catchment.

Impact of roof surface runoff on urban water quality

The pollutant impacts of urban stormwater runoff on receiving waters are well documented in research literature. However, it is road surfaces that are commonly identified as the significant pollutant source. This paper presents the outcomes of an extensive program of research into the role of roof surfaces in urban water quality with particular focus on solids, nutrients and organic carbon. The outcomes confirmed that roof surfaces play an important role in influencing the pollutant characteristics of urban stormwater runoff. Pollutant build-up and wash-off characteristics for roads and roof surfaces were found to be appreciably different. The pollutant wash-off characteristics exhibited by roof surfaces show that it influences the first flush phenomenon more significantly than road surfaces. In most urban catchments, as roof surfaces constitutes a higher fraction of impervious area compared to road surfaces, it is important that the pollutant generation role of roof surfaces is specifically taken into consideration in stormwater quality mitigation strategies.

Human proximal tubule epithelial cells modulate autologous dendritic cell function

Background We have previously demonstrated that human kidney proximal tubule epithelial cells (PTEC) are able to modulate autologous T and B lymphocyte responses. It is well established that dendritic cells (DC) are responsible for the initiation and direction of adaptive immune responses and that these cells occur in the renal interstitium in close apposition to PTEC under inflammatory disease settings. However, there is no information regarding the interaction of PTEC with DC in an autologous human context. Methods Human monocytes were differentiated into monocyte-derived DC (MoDC) in the absence or presence of primary autologous activated PTEC and matured with polyinosinic:polycytidylic acid [poly(I:C)], while purified, pre-formed myeloid blood DC (CD1c+ BDC) were cultured with autologous activated PTEC in the absence or presence of poly(I:C) stimulation. DC responses were monitored by surface antigen expression, cytokine secretion, antigen uptake capacity and allogeneic T-cell-stimulatory ability. Results The presence of autologous activated PTEC inhibited the differentiation of monocytes to MoDC. Furthermore, MoDC differentiated in the presence of PTEC displayed an immature surface phenotype, efficient phagocytic capacity and, upon poly(I:C) stimulation, secreted low levels of pro-inflammatory cytokine interleukin (IL)-12p70, high levels of anti-inflammatory cytokine IL-10 and induced weak Th1 responses. Similarly, pre-formed CD1c+ BDC matured in the presence of PTEC exhibited an immature tolerogenic surface phenotype, strong endocytic and phagocytic ability and stimulated significantly attenuated T-cell proliferative responses. Conclusions Our data suggest that activated PTEC regulate human autologous immunity via complex interactions with DC. The ability of PTEC to modulate autologous DC function has important implications for the dampening of pro-inflammatory immune responses within the tubulointerstitium in renal injuries. Further dissection of the mechanisms of PTEC modulation of autologous immune responses may offer targets for therapeutic intervention in renal medicine.

Gartner Surface Process Modelling movie

AR process modelling movie presented at Gartner BPM Summit in Sydney, August, 2011. Video showing us using the MS Surface at QUT to perform collaborative process modelling.

Silk fibroin in ocular surface reconstruction : what is its potential as a biomaterial in ophthalmics?

Hardly a month goes by within the scientific literature without some new material “X” being reported as a suitable material on which to grow cell type “Y”, for the potential purpose of treating disease “Z”. Thus when fibroin, a protein found in silk, was first proposed as a biomaterial for cell growth [1] it joined a long list of other materials of both natural as well as synthetic origin. Nevertheless, in the second decade of the Asian Century it is perhaps befitting that a material of so much importance to the continent’s cultural and economic history, should become the focus of cutting-edge biomedical research. Sentiments aside, however, silk fibroin possesses quite a unique combination of properties which make it a promising candidate for repairing the eye and especially for treating damage to the cornea, the transparent window at the front of the eye.

Numerical solution of stress intensity factors of multiple cracks in great number with eigen COD boundary integral equations

Based on the eigen crack opening displacement (COD) boundary integral equations, a newly developed computational approach is proposed for the analysis of multiple crack problems. The eigen COD particularly refers to a crack in an infinite domain under fictitious traction acting on the crack surface. With the concept of eigen COD, the multiple cracks in great number can be solved by using the conventional displacement discontinuity boundary integral equations in an iterative fashion with a small size of system matrix. The interactions among cracks are dealt with by two parts according to the distances of cracks to the current crack. The strong effects of cracks in adjacent group are treated with the aid of the local Eshelby matrix derived from the traction BIEs in discrete form. While the relatively week effects of cracks in far-field group are treated in the iteration procedures. Numerical examples are provided for the stress intensity factors of multiple cracks, up to several thousands in number, with the proposed approach. By comparing with the analytical solutions in the literature as well as solutions of the dual boundary integral equations, the effectiveness and the efficiencies of the proposed approach are verified.

Symptoms of heat illness in surface mine workers

Objective: To assess the symptoms of heat illness experienced by surface mine workers. Methods: Ninety-one surface mine workers across three mine sites in northern Australia completed a heat stress questionnaire evaluating their symptoms for heat illness. A cohort of 56 underground mine workers also participated for comparative purposes. Participants were allocated into asymptomatic, minor or moderate heat illness categories depending on the number of symptoms they reported. Participants also reported the frequency of symptom experience, as well as their hydration status (average urine colour). Results: Heat illness symptoms were experienced by 87 and 79 % of surface and underground mine workers, respectively (p = 0.189), with 81–82 % of the symptoms reported being experienced by miners on more than one occasion. The majority (56 %) of surface workers were classified as experiencing minor heat illness symptoms, with a further 31 % classed as moderate; 13 % were asymptomatic. A similar distribution of heat illness classification was observed among underground miners (p = 0.420). Only 29 % of surface miners were considered well hydrated, with 61 % minimally dehydrated and 10 % significantly dehydrated, proportions that were similar among underground miners (p = 0.186). Heat illness category was significantly related to hydration status (p = 0.039) among surface mine workers, but only a trend was observed when data from surface and underground miners was pooled (p = 0.073). Compared to asymptomatic surface mine workers, the relative risk of experiencing minor and moderate symptoms of heat illness was 1.5 and 1.6, respectively, when minimally dehydrated. Conclusions: These findings show that surface mine workers routinely experience symptoms of heat illness and highlight that control measures are required to prevent symptoms progressing to medical cases of heat exhaustion or heat stroke.

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell–cell and cell–matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cell infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell–cell and cell–matrix interactions, while syndecan-2 showed a predilection to associate with cell–matrix interactions during hard tissue formation.

Influence of pre-exsiting surface defects on the vibrational properties of Ag nanowires

Large-scale molecular dynamics simulations are performed to characterize the effects of pre-existing surface defects on the vibrational properties of Ag nanowires. It is found that the first order natural frequency of the nanowire appears insensitive to different surface defects, indicating a defect insensitivity property of the nanowire’s Young’s modulus. In the meanwhile, an increase of the quality (Q)-factor is observed due to the presence of defects. Particular, a beat phenomenon is observed for the nanowire with the presence of a surface edge defect, which is driven by a single actuation. It is concluded that different surface defects could act as an effective mean to tune the vibrational properties of nanowires. This study sheds lights on the better understanding of nanowire’s mechanical performance when surface defects are presented, which would benefit the development of nanowire-based devices.

In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.

Surface effects on the dual-mode vibration of <110> silver nanowires with different cross-sections

Dual-mode vibration of nanowires has been reported experimentally through actuation of the nanowire at its resonance frequency, which is expected to open up a variety of new modalities for the NEMS that could operate in the nonlinear regime. In the present work, we utilize large scale molecular dynamics simulations to investigate the dual-mode vibration of <110> Ag nanowires with triangular, rhombic and truncated rhombic cross-sections. By incorporating the generalized Young-Laplace equation into Euler-Bernoulli beam theory, the influence of surface effects on the dual-mode vibration is studied. Due to the different lattice spacing in principal axes of inertia of the {110} atomic layers, the NW is also modeled as a discrete system to reveal the influence from such specific atomic arrangement. It is found that the <110> Ag NW will under a dual-mode vibration if the actuation direction is deviated from the two principal axes of inertia. The predictions of the two first mode natural frequencies by the classical beam model appear underestimated comparing with the MD results, which are found to be enhanced by the discrete model. Particularly, the predictions by the beam theory with the contribution of surface effects are uniformly larger than the classical beam model, which exhibit better agreement with MD results for larger cross-sectional size. However, for ultrathin NWs, current consideration of surface effects is still experiencing certain inaccuracy. In all, for all different cross-sections, the inclusion of surface effects is found to reduce the difference between the two first mode natural frequencies. This trend is observed consistent with MD results. This study provides a first comprehensive investigation on the dual-mode vibration of <110> oriented Ag NWs, which is supposed to benefit the applications of NWs that acting as a resonating beam.

The interactions between insulin and androgens in progression to castrate resistant prostate cancer

An association between the metabolic syndrome and reduced testosterone levels has been identified, and a specific inverse relationship between insulin and testosterone levels suggests that an important metabolic crosstalk exists between these two hormonal axes; however, the mechanisms by which insulin and androgens may be reciprocally regulated are not well described. Androgen-dependant gene pathways regulate the growth and maintenance of both normal and malignant prostate tissue, and androgen-deprivation therapy (ADT) in patients exploits this dependence when used to treat recurrent and metastatic prostate cancer resulting in tumour regression. A major systemic side effect of ADT includes induction of key features of the metabolic syndrome and the consistent feature of hyperinsulinaemia. Recent studies have specifically identified a correlation between elevated insulin and high-grade PCa and more rapid progression to castrate resistant disease. This paper examines the relationship between insulin and androgens in the context of prostate cancer progression. Prostate cancer patients present a promising cohort for the exploration of insulin stabilising agents as adjunct treatments for hormone deprivation or enhancers of chemosensitivity for treatment of advanced prostate cancer.