In situ preparation and protein delivery of silicate/alginate composite microspheres with core-shell structure

It is predicted that with increased life expectancy in the developed world, there will be a greater demand for synthetic materials to repair or regenerate lost, injured or diseased bone (Hench & Thompson 2010). There are still few synthetic materials having true bone inductivity, which limits their application for bone regeneration, especially in large-size bone defects. To solve this problem, growth factors, such as bone morphogenetic proteins (BMPs), have been incorporated into synthetic materials in order to stimulate de novo bone formation in the center of large-size bone defects. The greatest obstacle with this approach is that the rapid diffusion of the protein from the carrier material, leading to a precipitous loss of bioactivity; the result is often insufficient local induction or failure of bone regeneration (Wei et al. 2007). It is critical that the protein is loaded in the carrier material in conditions which maintains its bioactivity (van de Manakker et al. 2009). For this reason, the efficient loading and controlled release of a protein from a synthetic material has remained a significant challenge. The use of microspheres as protein/drug carriers has received considerable attention in recent years (Lee et al. 2010; Pareta & Edirisinghe 2006; Wu & Zreiqat 2010). Compared to macroporous block scaffolds, the chief advantage of microspheres is their superior protein-delivery properties and ability to fill bone defects with irregular and complex shapes and sizes. Upon implantation, the microspheres are easily conformed to the irregular implant site, and the interstices between the particles provide space for both tissue and vascular ingrowth, which are important for effective and functional bone regeneration (Hsu et al. 1999). Alginates are natural polysaccharides and their production does not have the implicit risk of contamination with allo or xeno-proteins or viruses (Xie et al. 2010). Because alginate is generally cytocompatible, it has been used extensively in medicine, including cell therapy and tissue engineering applications (Tampieri et al. 2005; Xie et al. 2010; Xu et al. 2007). Calcium cross-linked alginate hydrogel is considered a promising material as a delivery matrix for drugs and proteins, since its gel microspheres form readily in aqueous solutions at room temperature, eliminating the need for harsh organic solvents, thereby maintaining the bioactivity of proteins in the process of loading into the microspheres (Jay & Saltzman 2009; Kikuchi et al. 1999). In addition, calcium cross-linked alginate hydrogel is degradable under physiological conditions (Kibat PG et al. 1990; Park K et al. 1993), which makes alginate stand out as an attractive candidate material for the protein carrier and bone regeneration (Hosoya et al. 2004; Matsuno et al. 2008; Turco et al. 2009). However, the major disadvantages of alginate microspheres is their low loading efficiency and also rapid release of proteins due to the mesh-like networks of the gel (Halder et al. 2005). Previous studies have shown that a core-shell structure in drug/protein carriers can overcome the issues of limited loading efficiencies and rapid release of drug or protein (Chang et al. 2010; Molvinger et al. 2004; Soppimath et al. 2007). We therefore hypothesized that introducing a core-shell structure into the alginate microspheres could solve the shortcomings of the pure alginate. Calcium silicate (CS) has been tested as a biodegradable biomaterial for bone tissue regeneration. CS is capable of inducing bone-like apatite formation in simulated body fluid (SBF) and its apatite-formation rate in SBF is faster than that of Bioglass® and A-W glass-ceramics (De Aza et al. 2000; Siriphannon et al. 2002). Titanium alloys plasma-spray coated with CS have excellent in vivo bioactivity (Xue et al. 2005) and porous CS scaffolds have enhanced in vivo bone formation ability compared to porous β-tricalcium phosphate ceramics (Xu et al. 2008). In light of the many advantages of this material, we decided to prepare CS/alginate composite microspheres by combining a CS shell with an alginate core to improve their protein delivery and mineralization for potential protein delivery and bone repair applications

Single-crystal Raman spectroscopy of natural schafarzikite FeSb2O4 from Pernek, Slovak Republic

The single crystal Raman spectra of natural mineral schafarzikite FeSb2O4 from the Pernek locality of the Slovak Republic are presented for the first time. Raman spectra of natural mineral apuanite Fe2+Fe43+Sb4O12S, originating from the Apuan Alps in Italy, as well as spectra of synthetic ZnSb2O4 and arsenite mineral trippkeite CuAs2O4 are also presented for the first time. The spectra of the antimonite minerals are characterized by a strong band in the region 660 – 680 cm-1 with shoulders on either side, and a band of medium intensity near 300 cm-1. The spectrum of the arsenite mineral is characterized by a medium band near 780 cm-1 with a shoulder on the high wavenumber side and a strong band at 370 cm-1. Assignments are proposed based on the spectral comparison between the compounds, symmetry modes of the bands and prior literature. The single crystal spectra of schafarzikite showed good mode separation, allowing bands to be assigned a symmetry species of A1g, B1g, B2g or Eg.

Nursing and competencies - a natural fit : the politics of skill/competency formation in nursing

The last two decades have seen a significant restructuring of work across Australia and other industrialised economies, a critical part of which has been the appearance of competency based education and assessment. The competency movement is about creating a more flexible and mobile labour force to increase productivity and it does so by redefining work as a set of transferable or ‘soft’ generic skills that are transportable and are the possession of the individual. This article sought to develop an analysis of competency based clinical assessment of nursing students across a bachelor of nursing degree course. This involved an examination of a total of 406 clinical assessment tools that covered the years 1992-2009 and the three years of a bachelor degree. Data analysis generated three analytical findings: the existence of a hierarchy of competencies that prioritises soft skills over intellectual and technical skills; the appearance of skills as personal qualities or individual attributes; and the absence of context in assessment. The article argues that the convergence in nursing of soft skills and the professionalisation project reform has seen the former give legitimacy to the enduring invisibility and devaluation of nursing work.

Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia

The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.

Active transonic aerofoil design optimization using robust multiobjective evolutionary algorithms

The use of adaptive wing/aerofoil designs is being considered, as they are promising techniques in aeronautic/ aerospace since they can reduce aircraft emissions and improve aerodynamic performance of manned or unmanned aircraft. This paper investigates the robust design and optimization for one type of adaptive techniques: active flow control bump at transonic flow conditions on a natural laminar flow aerofoil. The concept of using shock control bump is to control supersonic flow on the suction/pressure side of natural laminar flow aerofoil that leads to delaying shock occurrence (weakening its strength) or boundary layer separation. Such an active flow control technique reduces total drag at transonic speeds due to reduction of wave drag. The location of boundary-layer transition can influence the position and structure of the supersonic shock on the suction/pressure side of aerofoil. The boundarylayer transition position is considered as an uncertainty design parameter in aerodynamic design due to the many factors, such as surface contamination or surface erosion. This paper studies the shock-control-bump shape design optimization using robust evolutionary algorithms with uncertainty in boundary-layer transition locations. The optimization method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing, and asynchronous evaluation. The use of adaptive wing/aerofoil designs is being considered, as they are promising techniques in aeronautic/ aerospace since they can reduce aircraft emissions and improve aerodynamic performance of manned or unmanned aircraft. This paper investigates the robust design and optimization for one type of adaptive techniques: active flow control bump at transonic flow conditions on a natural laminar flow aerofoil. The concept of using shock control bump is to control supersonic flow on the suction/pressure side of natural laminar flow aerofoil that leads to delaying shock occurrence (weakening its strength) or boundary-layer separation. Such an active flow control technique reduces total drag at transonic speeds due to reduction of wave drag. The location of boundary-layer transition can influence the position and structure of the supersonic shock on the suction/pressure side of aerofoil. The boundarylayer transition position is considered as an uncertainty design parameter in aerodynamic design due to the many factors, such as surface contamination or surface erosion. This paper studies the shock-control-bump shape design optimization using robust evolutionary algorithms with uncertainty in boundary-layer transition locations. The optimization method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing, and asynchronous evaluation. Two test cases are conducted: the first test assumes the boundary-layer transition position is at 45% of chord from the leading edge, and the second test considers robust design optimization for the shock control bump at the variability of boundary-layer transition positions. The numerical result shows that the optimization method coupled to uncertainty design techniques produces Pareto optimal shock-control-bump shapes, which have low sensitivity and high aerodynamic performance while having significant total drag reduction.

Unsteady natural convection in a triangular enclosure under isothermal heating

The fluid flow and heat transfer inside a triangular enclosure due to instantaneous heating on the inclined walls are investigated using an improved scaling analysis and direct numerical simulations. The development of the unsteady natural convection boundary layer under the inclined walls may be classified into three distinct stages including a start-up stage, a transitional stage and a steady state stage, which can be clearly identified in the analytical and numerical results. A new triple-layer integral approach of scaling analysis has been considered to obtain major scaling relations of the velocity, thicknesses, Nusselt number and the flow development time of the natural convection boundary layer and verified by direct numerical simulations over a wide range of flow parameters.

Scaling of natural convection of an inclined flat plate : ramp cooling condition

A scaling analysis is performed for the transient boundary layer established adjacent to an inclined flat plate following a ramp cooling boundary condition. The imposed wall temperature decreases linearly up to a specific value over a specific time. It is revealed that if the ramp time is sufficiently large then the boundary layer reaches quasi-steady mode before the growth of the temperature is finished. However, if the ramp time is shorter then the steady state of the boundary layer may be reached after the growth of the temperature is completed. In this case, the ultimate steady state is the same as if the start up had been instantaneous. Note that the cold boundary layer adjacent to the plate is potentially unstable to Rayleigh-Bénard instability if the Rayleigh number exceeds a certain critical value for this cooling case. The onset of instability may set in at different stages of the boundary layer development. A proper identification of the time when the instability may set in is discussed. A numerical verification of the time for the onset of instability is presented in this study. Different flow regimes based on the stability of the boundary layer have also been discussed with numerical results.

Natural convection boundary-layer adjacent to an inclined flat plate subject to sudden and ramp heating

The natural convection thermal boundary layer adjacent to an inclined flat plate subject to sudden heating and a temperature boundary condition which follows a ramp function up until a specified time and then remains constant is investigated. The development of the flow from start-up to a steady-state has been described based on scaling analyses and verified by numerical simulations. Different flow regimes based on the Rayleigh number are discussed with numerical results for both boundary conditions. For ramp heating, the boundary layer flow depends on the comparison of the time at which the ramp heating is completed and the time at which the boundary layer completes its growth. If the ramp time is long compared with the steady state time, the layer reaches a quasi steady mode in which the growth of the layer is governed solely by the thermal balance between convection and conduction. On the other hand, if the ramp is completed before the layer becomes steady; the subsequent growth is governed by the balance between buoyancy and inertia, as for the case of instantaneous heating.

Scaling of natural convection of an inclined flat plate : sudden cooling condition

The natural convection boundary layer adjacent to an inclined plate subject to sudden cooling boundary condition has been studied. It is found that the cold boundary layer adjacent to the plate is potentially unstable to Rayleigh-Bénard instability if the Rayleigh number exceeds a certain critical value. A scaling relation for the onset of instability of the boundary layer is achieved. The scaling relations have been developed by equating important terms of the governing equations based on the development of the boundary layer with time. The flow adjacent to the plate can be classified broadly into a conductive, a stable convective or an unstable convective regime determined by the Rayleigh number. Proper scales have been established to quantify the flow properties in each of these flow regimes. An appropriate identification of the time when the instability may set in is discussed. A numerical verification of the time for the onset of instability is also presented in this study. Different flow regimes based on the stability of the boundary layer have been discussed with numerical results.

Natural convection in attic-shaped spaces subject to sudden and ramp heating boundary conditions

In this study, a discussion of the fluid dynamics in the attic space is reported, focusing on its transient response to sudden and linear changes of temperature along the two inclined walls. The transient behaviour of an attic space is relevant to our daily life. The instantaneous and non-instantaneous (ramp) heating boundary condition is applied on the sloping walls of the attic space. A theoretical understanding of the transient behaviour of the flow in the enclosure is performed through scaling analysis. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the heating-up of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Natural convection in attics subject to instantaneous and ramp cooling boundary conditions

A fundamental study of the fluid dynamics inside an attic shaped triangular enclosure with cold upper walls and adiabatic horizontal bottom wall is reported in this study. The transient behaviour of the attic fluid which is relevant to our daily life is examined based on a scaling analysis. The transient phenomenon begins with the instantaneous cooling and the cooling with linear decreases of temperature up to some specific time (ramp time) and then maintain constant of the upper sloped walls. It is shown that both inclined walls develop a thermal boundary layer whose thicknesses increase towards steady-state or quasi-steady values. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the cooling-down of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Natural convection and heat transfer in attics subject to periodic thermal forcing

The heat transfer through the attics of buildings under realistic thermal forcing has been considered in this study. A periodic temperature boundary condition is applied on the sloping walls of the attic to show the basic flow features in the attic space over diurnal cycles. The numerical results reveal that, during the daytime heating stage, the flow in the attic space is stratified; whereas at the night-time cooling stage, the flow becomes unstable. A symmetrical solution is seen for relatively low Rayleigh numbers. However, as the Ra gradually increases, a transition occurs at a critical value of Ra. Above this critical value, an asymmetrical solution exhibiting a pitchfork bifurcation arises at the night-time. It is also found that the calculated heat transfer rate at the night-time cooling stage is much higher than that during the daytime heating stage.