Size and habit of mineral particles in bone and mineralized callus during bone healing in sheep

Bone healing is known to occur through the successive formation and resorption of various tissues with different structural and mechanical properties. To get a better insight into this sequence of events, we used environmental scanning electron microscopy (ESEM) together with scanning small-angle X-ray scattering (sSAXS) to reveal the size and orientation of bone mineral particles within the regenerating callus tissues at different healing stages (2, 3, 6, and 9 weeks). Sections of 200 µm were cut from embedded blocks of midshaft tibial samples in a sheep osteotomy model with an external fixator. Regions of interest on the medial side of the proximal fragment were chosen to be the periosteal callus, middle callus, intercortical callus, and cortex. Mean thickness (T parameter), degree of alignment (ρ parameter), and predominant orientation (ψ parameter) of mineral particles were deduced from resulting sSAXS patterns with a spatial resolution of 200 µm. 2D maps of T and ρ overlapping with ESEM images revealed that the callus formation occurred in two waves of bone formation, whereby a highly disordered mineralized tissue was deposited first, followed by a bony tissue with more lamellar appearance in the ESEM and where the mineral particles were more aligned, as revealed by sSAXS. As a consequence, degree of alignment and mineral particle size within the callus increased with healing time, whereas at any given moment there were structural gradients, for example, from periosteal toward the middle callus.

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

Removing barriers to protection at the exported border : visas, carrier sanctions, and international obligation

Asylum is being gradually denuded of the national institutional mechanisms (judicial, legislative and administrative) that provide the framework for a fair and effective asylum hearing. In this sense, there is an ongoing ‘denationalization’ or ‘deformalization’ of the asylum process. This chapter critically examines one of the linchpins of this trend: the erection of pre-entry measures at ports of embarkation in order to prevent asylum seekers from physically accessing the territory of the state. Pre-entry measures comprise the core requirement that foreigners possess an entry visa granting permission to enter the state of destination. Visa requirements are increasingly implemented by immigration officials posted abroad or by officials of transit countries pursuant to bilateral agreements (so-called ‘juxtaposed’ immigration controls). Private carriers, which are subject to sanctions if they bring persons to a country who do not have permission to enter, also engage in a form of de facto immigration control on behalf of states. These measures constitute a type of ‘externalized’ or ‘exported’ border that pushes the immigration boundaries of the state as far from its physical boundaries as possible. Pre-entry measures have a crippling impact on the ability of asylum seekers to access the territory of states to claim asylum. In effect, states have ‘externalized’ asylum by replacing the legal obligation on states to protect refugees arriving at ports of entry with what are perceived to be no more than moral obligations towards asylum seekers arriving at the external border of the state.

Thermal performance optimization of building aspect ratio and south window size in five cities having different climatic characteristics of Turkey

The aim of the study is to establish optimum building aspect ratios and south window sizes of residential buildings from thermal performance point of view. The effects of 6 different building aspect ratios and eight different south window sizes for each building aspect ratio are analyzed for apartments located at intermediate floors of buildings, by the aid of the computer based thermal analysis program SUNCODE-PC in five cities of Turkey: Erzurum, Ankara, Diyarbakir, Izmir, and Antalya. The results are evaluated in terms of annual energy consumption and the optimum values are driven. Comparison of optimum values and the total energy consumption rates is made among the analyzed cities.

The sample complexity of pattern classification with neural networks: the size of the weights is more important than the size of the network

Sample complexity results from computational learning theory, when applied to neural network learning for pattern classification problems, suggest that for good generalization performance the number of training examples should grow at least linearly with the number of adjustable parameters in the network. Results in this paper show that if a large neural network is used for a pattern classification problem and the learning algorithm finds a network with small weights that has small squared error on the training patterns, then the generalization performance depends on the size of the weights rather than the number of weights. For example, consider a two-layer feedforward network of sigmoid units, in which the sum of the magnitudes of the weights associated with each unit is bounded by A and the input dimension is n. We show that the misclassification probability is no more than a certain error estimate (that is related to squared error on the training set) plus A3 √((log n)/m) (ignoring log A and log m factors), where m is the number of training patterns. This may explain the generalization performance of neural networks, particularly when the number of training examples is considerably smaller than the number of weights. It also supports heuristics (such as weight decay and early stopping) that attempt to keep the weights small during training. The proof techniques appear to be useful for the analysis of other pattern classifiers: when the input domain is a totally bounded metric space, we use the same approach to give upper bounds on misclassification probability for classifiers with decision boundaries that are far from the training examples.

An empirical study of applying ISO 9001 elements in large size Indonesian contractors

The effective implementation of such an ISO 9001 Quality Management System (QMS) in construction companies requires a proper and full implementation of the system to allow companies to improve the way they operate, by this means increasing profitability and market share, producing innovative and sustainable construction products, or improving employee and customer satisfaction. In light of this, this paper discusses the current status of QMS implementation, particularly related to the twenty elements of ISO 9001 within the grade 7 (G-7) category of Indonesian construction companies. A survey was conducted involving 403 respondents from 77 companies, to solicit an evaluation of the current implementation levels of the ISO 9001 elements. The survey findings indicated that for a large percentage of the sector surveyed they had ‘not so fully implemented’ the elements. Scrutiny of the data had also indicated elements that are ‘minimally implemented’, whilst none of the elements fell in the category of ‘fully implemented’. Based on these findings, it is suggested that the G-7 contractors may need to fully commit to practicing control of customer-supplied product and statistical techniques in order to enhance an effective implementation of ISO 9001 elements for ensuring better quality performance. These two elements are recognized as the least implemented of the quality elements.