Interleukin-1β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism

One of the hallmarks of progressive renal disease is the development of tubulointerstitial fibrosis. This is frequently preceded by macrophage infiltration, raising the possibility that macrophages relay fibrogenic signals to resident tubulointerstitial cells. The aim of this study was to investigate the potentially fibrogenic role of interleukin-1beta (IL-1beta), a macrophage-derived inflammatory cytokine, on cortical fibroblasts (CFs). Primary cultures of human renal CFs were established and incubated for 24 hours in the presence or absence of IL-1beta. We found that IL-1beta significantly stimulated DNA synthesis (356.7% +/- 39% of control, P <.003), fibronectin secretion (261.8 +/- 11% of control, P <.005), collagen type 1 production, (release of procollagen type 1 C-terminal-peptide, 152.4% +/- 26% of control, P <.005), transforming growth factor-beta (TGF-beta) secretion (211% +/- 37% of control, P <.01), and nitric oxide (NO) production (342.8% +/- 69% of control, P <.002). TGF-beta (1 ng/mL) and the phorbol ester phorbol 12-myristate 13-acetate (PMA, 25 nmol/L) produced fibrogenic effects similar to those of IL-1beta. Neither a NO synthase inhibitor (N(G)-methyl-l-arginine, 1 mmol/L) nor a protein kinase C (PKC) inhibitor (bis-indolylmaleimide 1, 1 micromol/L) altered the enhanced level of fibronectin secretion or DNA synthesis seen in response to IL-1beta treatment. However, addition of a TGF-beta-neutralizing antibody significantly reduced IL-1beta-induced fibronectin secretion (IL-1beta + IgG, 262% +/- 72% vs IL-1beta + alphaTGF-beta 156% +/- 14%, P <.02), collagen type 1 production (IL-1beta + IgG, 176% +/- 28% vs IL-1beta + alphaTGF-beta, 120% +/- 14%, P <.005) and abrogated IL-1beta-induced DNA synthesis (245% +/- 49% vs 105% +/- 21%, P <.005). IL-1beta significantly stimulated CF DNA synthesis and production of fibronectin, collagen type 1, TGFbeta, and NO. The fibrogenic and proliferative action of IL-1beta on CF appears not to involve activation of PKC or production of NO but is at least partly TGFbeta-dependent.

Matrix metalloproteinases during wound healing - a double edged sword

The extracellular matrix (ECM) provides a framework for cells and gives skin its tensile strength and elasticity. Loss of its integrity necessitates the clearing of damaged components and the deposition of firstly a provisional matrix and later remodelling of the ECM to support a functionally intact tissue. Matrix metalloproteinases (MMPs) are an important family of enzymes that function in the breakdown of the ECM and modulate the function of many biologically active molecules housed in the ECM. Through their enzymatic actions MMPs play a role in fundamental processes such as immune cell infiltration and ECM remodelling during wound repair. Their tight control is necessary for timely wound healing and excessive MMP activity participates in the development and persistence of chronic wounds, while reduced activity contributes to fibrosis. A number of inhibitors have been designed to target this activity and improve wound healing with limited success. Novel strategies are currently being investigated to improve wound healing by targeting MMP modulating molecules.

Photocatalysis on supported gold and silver nanoparticles under ultraviolet and visible light irradiation

Studies of the optical properties and catalytic capabilities of noble metal nanoparticles (NPs), such as gold (Au) and silver (Ag), have formed the basis for the very recent fast expansion of the field of green photocatalysis: photocatalysis utilizing visible and ultraviolet light, a major part of the solar spectrum. The reason for this growth is the recognition that the localised surface plasmon resonance (LSPR) effect of Au NPs and Ag NPs can couple the light flux to the conduction electrons of metal NPs, and the excited electrons and enhanced electric fields in close proximity to the NPs can contribute to converting the solar energy to chemical energy by photon-driven photocatalytic reactions. Previously the LSPR effect of noble metal NPs was utilized almost exclusively to improve the performance of semiconductor photocatalysts (for example, TiO2 and Ag halides), but recently, a conceptual breakthrough was made: studies on light driven reactions catalysed by NPs of Au or Ag on photocatalytically inactive supports (insulating solids with a very wide band gap) have demonstrated that these materials are a class of efficient photocatalysts working by mechanisms distinct from those of semiconducting photocatalysts. There are several reasons for the significant photocatalytic activity of Au and Ag NPs. (1) The conduction electrons of the particles gain the irradiation energy, resulting in high energy electrons at the NP surface which is desirable for activating molecules on the particles for chemical reactions. (2) In such a photocatalysis system, both light harvesting and the catalysing reaction take place on the nanoparticle, and so charge transfer between the NPs and support is not a prerequisite. (3) The density of the conduction electrons at the NP surface is much higher than that at the surface of any semiconductor, and these electrons can drive the reactions on the catalysts. (4) The metal NPs have much better affinity than semiconductors to many reactants, especially organic molecules. Recent progress in photocatalysis using Au and Ag NPs on insulator supports is reviewed. We focus on the mechanism differences between insulator and semiconductor-supported Au and Ag NPs when applied in photocatalytic processes, and the influence of important factors, light intensity and wavelength, in particular estimations of light irradiation contribution, by calculating the apparent activation energies of photo reactions and thermal reactions.

Estimation of vibration amplitude in Fourier domain optical coherence tomography interferometric signals from Doppler spectrum

In presented method combination of Fourier and Time domain detection enables to broaden the effective bandwidth for time dependent Doppler Signal that allows for using higher-order Bessel functions to calculate unambiguously the vibration amplitudes.

A deconvolution method for deriving the transit time spectrum for ultrasound propagation through cancellous bone replica models

The acceptance of broadband ultrasound attenuation for the assessment of osteoporosis suffers from a limited understanding of ultrasound wave propagation through cancellous bone. It has recently been proposed that the ultrasound wave propagation can be described by a concept of parallel sonic rays. This concept approximates the detected transmission signal to be the superposition of all sonic rays that travel directly from transmitting to receiving transducer. The transit time of each ray is defined by the proportion of bone and marrow propagated. An ultrasound transit time spectrum describes the proportion of sonic rays having a particular transit time, effectively describing lateral inhomogeneity of transit times over the surface of the receiving ultrasound transducer. The aim of this study was to provide a proof of concept that a transit time spectrum may be derived from digital deconvolution of input and output ultrasound signals. We have applied the active-set method deconvolution algorithm to determine the ultrasound transit time spectra in the three orthogonal directions of four cancellous bone replica samples and have compared experimental data with the prediction from the computer simulation. The agreement between experimental and predicted ultrasound transit time spectrum analyses derived from Bland–Altman analysis ranged from 92% to 99%, thereby supporting the concept of parallel sonic rays for ultrasound propagation in cancellous bone. In addition to further validation of the parallel sonic ray concept, this technique offers the opportunity to consider quantitative characterisation of the material and structural properties of cancellous bone, not previously available utilising ultrasound.

A nation’s role in addressing base erosion and profit shifting : balancing sovereignty with international collaboration and coordination

The notion of sovereignty is central to any international tax issue. While a nation is free to design its tax laws as it sees fit and raise revenue in accordance with the needs of its citizens, it is not possible to undertake such a task in isolation. In a world of cross-border investments and business transactions, all tax regimes impact on one another. Tax interactions between sovereign states cannot be avoided. Ultimately, the interactions mean that a nation must decide whether to engage in both collaboration and coordination with other nations and supranational bodies alike or maintain an individualised stance in relation to its tax policy. Whatever the decision, there is arguably an exercise in national sovereignty in some form. In the context of an international tax regime, whether that regime is interpreted broadly as meaning international norms generally adopted by nations around the world or domestic regimes legislating for cross-border transactions, rhetoric around national fiscal sovereignty takes on many different forms. At one end of the spectrum it is relied upon by financial secrecy jurisdictions (tax havens) as a defence to their position on the basis that ‘other’ nations cannot interfere with the fiscal sovereignty of a jurisdiction. At the other end of the spectrum, it is argued that profit shifting and international tax avoidance if not stopped is, in and of itself, a threat to a nation’s fiscal sovereignty on the basis that it threatens the ability to tax and raise the revenue needed. This paper considers a modern conceptualisation of sovereignty along with its role within international tax coordination and collaboration to argue that a move towards a more unified approach to addressing international base erosion and profit shifting may be the ultimate exercise of national fiscal sovereignty. By using the current transfer pricing regime as a case study, this paper posits that it is not merely enough to have international agreement on allocation rules to be applied, but that the ultimate exercise of national sovereignty is political agreement with other states to ensure that it is governments which determine the allocational basis of worldwide profits to be taxed. In doing so, it is demonstrated that the arm’s length pricing requirement of the current transfer pricing regime, rather than providing governments with the ability to determine the location of profits, is providing multinational entities with the ultimate power to determine that location. If left unchecked, this will eventually erode a nation’s ability to capture the required tax revenue and, as a consequence, may be deemed a failure by nation states to exercise their fiscal sovereignty.

Transfer pricing and multinational financial institutions : the case for replacing arm’s length price with a unitary approach

The international tax system, designed a century ago, has not kept pace with the modern multinational entity rendering it ineffective in taxing many modern businesses according to economic activity. One of those modern multinational entities is the multinational financial institution (MNFI). The recent global financial crisis provides a particularly relevant and significant example of the failure of the current system on a global scale. The modern MNFI is increasingly undertaking more globalised and complex trading operations. A primary reason for the globalisation of financial institutions is that they typically ‘follow-the-customer’ into jurisdictions where international capital and international investors are required. The International Monetary Fund (IMF) recently reported that from 1995-2009, foreign bank presence in developing countries grew by 122 per cent. The same study indicates that foreign banks have a 20 per cent market share in OECD countries and 50 per cent in emerging markets and developing countries. Hence, most significant is that fact that MNFIs are increasingly undertaking an intermediary role in developing economies where they are financing core business activities such as mining and tourism. IMF analysis also suggests that in the future, foreign bank expansion will be greatest in emerging economies. The difficulties for developing countries in applying current international tax rules, especially the current traditional transfer pricing regime, are particularly acute in relation to MNFIs, which are the biggest users of tax havens and offshore finance. This paper investigates whether a unitary taxation approach which reflects economic reality would more easily and effectively ensure that the profits of MNFIs are taxed in the jurisdictions which give rise to those profits. It has previously been argued that the uniqueness of MNFIs results in a failure of the current system to accurately allocate profits and that unitary tax as an alternative could provide a sounder allocation model for international tax purposes. This paper goes a step further, and examines the practicalities of the implementation of unitary taxation for MNFIs in terms of the key components of such a regime, along with their their implications. This paper adopts a two-step approach in considering the implications of unitary taxation as a means of improved corporate tax coordination which requires international acceptance and agreement. First, the definitional issues of the unitary MNFI are examined and second, an appropriate allocation formula for this sector is investigated. To achieve this, the paper asks first, how the financial sector should be defined for the purposes of unitary taxation and what should constitute a unitary business for that sector and second, what is the ‘best practice’ model of an allocation formula for the purposes of the apportionment of the profits of the unitary business of a financial institution.

Hybrid multi-channel cooperative spectrum sensing to satisfy channel target

Spectrum sensing of multiple primary user channels is a crucial function in cognitive radio networks. In this paper we propose an optimal, sensing resource allocation algorithm for multi-channel cooperative spectrum sensing. The channel target is implemented as an objective and constraint to ensure a pre-determined number of empty channels are detected for secondary user network operations. Based on primary user traffic parameters, we calculate the minimum number of primary user channels that must be sensed to satisfy the channel target. We implement a hybrid sensing structure by grouping secondary user nodes into clusters and assign each cluster to sense a different primary user channels. We then solve the resource allocation problem to find the optimal sensing configuration and node allocation to minimise sensing duration. Simulation results show that the proposed algorithm requires the shortest sensing duration to achieve the channel target compared to existing studies that require long sensing and cannot guarantee the target.

A dedicated retrieval and transfer service : the QUARTS project

Background The transfer and/or retrieval of a critically patient is inherently dangerous not only for the patient but for staff as well. The quality and experience of unplanned transfers can influence patient mortality and morbidity. However, international evidence suggests that dedicated transfer/retrieval teams can improve mortality and morbidity outcomes. Aims The initial aim of this paper is to describe an in-house competency-based training programme, which encompasses the STaR approach to develop members of our existing nursing team to be part of the dedicated transfer/retrieval service. The paper also presents audit data findings which examined the source of referrals, number of patients actually transferred and clinical status of those being transferred. Results Audit data illustrate that the most frequent source of referrals comes from Accident and Emergency and the Surgical Directorate with the most common presenting condition being cardio-respiratory failure or arrest. Audit data reveal that the number of patients actually transferred or retrieved is relatively small (33%) compared with the overall number of requests for assistance. However, 36% of those patients transferred had a level 2 or level 3 acuity status that necessitated the admission to a critical care area. Conclusions A number of studies have concluded that the ill-experienced and ill-equipped transfer team can place patients’ at serious risk of harm. Whether planned or unplanned, dedicated critical care transfer/retrieval teams have been shown to reduce patient mortality and morbidity.

A nation's role in addressing base erosion and profit shifting : sovereignty in relation to transfer pricing

The notion of sovereignty is central to any international tax issue. While a nation is free to design its tax laws as it sees fit and raise revenue in accordance with the needs of its citizens, it is not possible to undertake such a task in isolation. Tax interactions between sovereign states cannot be avoided. Ultimately, the interactions mean that a nation must decide whether or engage in both collaboration and co ordination with other nations and supranational bodies alike or maintain a unilateral stance in relation to its tax policy. This article considers a modern conceptualisation of sovereignty to argue that a move towards a more unified approach to addressing international base erosion and profit sharing may be the ultimate exercise of national fiscal sovereignty.

Knowledge transfer through dual degree programs : perspectives from Indonesian universities

The thesis provides an Indonesian perspective into the rationales and outcomes of cooperation between Indonesian and Australian universities. It demonstrates that Indonesian universities participating in this study have actively pursued their institutional agenda to bring benefits from the cooperation with the international partners and engaged in knowledge transfer with these partners to develop their capacity. It particularly investigates the knowledge transfer processes between Indonesian and Australian universities through dual degree program partnerships.

Atomistic simulation of surface functionalization on the interfacial properties of graphene-polymer nanocomposites

Graphene has been increasingly used as nano sized fillers to create a broad range of nanocomposites with exceptional properties. The interfaces between fillers and matrix play a critical role in dictating the overall performance of a composite. However, the load transfer mechanism along graphene-polymer interface has not been well understood. In this study, we conducted molecular dynamics simulations to investigate the influence of surface functionalization and layer length on the interfacial load transfer in graphene polymer nanocomposites. The simulation results show that oxygen-functionalized graphene leads to larger interfacial shear force than hydrogen-functionalized and pristine ones during pull-out process. The increase of oxygen coverage and layer length enhances interfacial shear force. Further increase of oxygen coverage to about 7% leads to a saturated interfacial shear force. A model was also established to demonstrate that the mechanism of interfacial load transfer consists of two contributing parts, including the formation of new surface and relative sliding along the interface. These results are believed to be useful in development of new graphene-based nanocomposites with better interfacial properties.

Mesenchymal stem cells, neural lineage potential, heparan sulfate proteoglycans and the matrix

Along with the tri-lineage of bone, cartilage and fat, human mesenchymal stem cells (hMSCs) retain neural lineage potential. Multiple factors have been described that influence lineage fate of hMSCs including the extracellular microenvironment or niche. The niche includes the extracellular matrix (ECM) providing structural composition, as well as other associated proteins and growth factors, which collectively influence hMSC stemness and lineage specification. As such, lineage specific differentiation of MSCs is mediated through interactions including cell–cell and cell–matrix, as well as through specific signalling pathways triggering downstream events. Proteoglycans (PGs) are ubiquitous within this microenvironment and can be localised to the cell surface or embedded within the ECM. In addition, the heparan sulfate (HS) and chondroitin sulfate (CS) families of PGs interact directly with a number of growth factors, signalling pathways and ECM components including FGFs, Wnts and fibronectin. With evidence supporting a role for HSPGs and CSPGs in the specification of hMSCs down the osteogenic, chondrogenic and adipogenic lineages, along with the localisation of PGs in development and regeneration, it is conceivable that these important proteins may also play a role in the differentiation of hMSCs toward the neuronal lineage. Here we summarise the current literature and highlight the potential for HSPG directed neural lineage fate specification in hMSCs, which may provide a new model for brain damage repair.

Reversible addition fragmentation chain transfer (RAFT) polymerization : mechanism, process and applications

The present article gives an overview of the reversible addition fragmentation chain transfer (RAFT) process. RAFT is one of the most versatile living radical polymerization systems and yields polymers of predictable chain length and narrow molecular weight distribution. RAFT relies on the rapid exchange of thiocarbonyl thio groups between growing polymeric chains. The key strengths of the RAFT process for polymer design are its high tolerance of monomer functionality and reaction conditions, the wide range of well-controlled polymeric architectures achievable, and its (in-principle) non-rate-retarding nature. This article introduces the mechanism of polymerization, the range of polymer molecular weights achievable, the range of monomers in which polymerization is controlled by RAFT, the various polymeric architectures that can be obtained, the type of end-group functionalities available to RAFT-made polymers, and the process of RAFT polymerization.

Eigenstrain boundary integral equations with local Eshelby matrix for stress analysis of ellipsoidal particles

Aiming at the large scale numerical simulation of particle reinforced materials, the concept of local Eshelby matrix has been introduced into the computational model of the eigenstrain boundary integral equation (BIE) to solve the problem of interactions among particles. The local Eshelby matrix can be considered as an extension of the concepts of Eshelby tensor and the equivalent inclusion in numerical form. Taking the subdomain boundary element method as the control, three-dimensional stress analyses are carried out for some ellipsoidal particles in full space with the proposed computational model. Through the numerical examples, it is verified not only the correctness and feasibility but also the high efficiency of the present model with the corresponding solution procedure, showing the potential of solving the problem of large scale numerical simulation of particle reinforced materials.