Mesenchymal stem cells

Cell based therapies as they apply to tissue engineering and regenerative medicine, require cells capable of self renewal and differentiation, and a prerequisite is to be able to prepare an effective dose of ex vivo expanded cells for autologous transplants. The in vivo identification of a source of physiologically relevant cell types suitable for cell therapies therefore figures as an integral part of tissue engineering. Stem cells serve as a reserve for biological repair, having the potential to differentiate into a number of specialised cell types within the body; they therefore represent the most useful candidates for cell based therapies. The primary goal of stem cell research is to produce cells that are both patient specific, as well as having properties suitable for the specific conditions for which they are intended to remedy. From a purely scientific perspective, stem cells allow scientists to gain a deeper understanding of developmental biology and regenerative therapies. Stem cells have acquired a number of uses for applications in regenerative medicine, immunotherapy, gene therapy, but it is in the area of tissue engineering that they generate most excitement, primarily as a result of their capacity for self-renewal and pluripotency. A unique feature of stem cells is their ability to maintain an uncommitted quiescent state in vivo and then, once triggered by conditions such as disease, injury or natural wear or tear, serve as a reservoir and natural support system to replenish lost cells. Although these cells retain the plasticity to differentiate into various tissues, being able to control this differentiation process is still one of the biggest challenges facing stem cell research. In an effort to harness the potential of these cells a number of studies have been conducted using both embryonic/foetal and adult stem cells. The use of embryonic stem cells (ESC) have been hampered by strong ethical and political concerns, this despite their perceived versatility due to their pluripotency. Ethical issues aside, other concerns raised with ESCs relates to the possibility of tumorigenesis, immune rejection and complications with immunosuppressive therapies, all of which adds layers of complications to the application ESC in research and which has led to the search for alternative sources for stem cells. The adult tissues in higher organisms harbours cells, termed adult stem cells, and these cells are reminiscent of unprogrammed stem cells. A number of sources of adult stem cells have been described. Bone marrow is by far the most accessible source of two potent populations of adult stem cells, namely haematopoietic stem cells (HSCs) and bone marrow mesenchymal stem cells (BMSCs). Autologously harvested adult stem cells can, in contrast to embryonic stem cells, readily be used in autografts, since immune rejection is not an issue; and their use in scientific research has not attracted the ethical concerns which have been the case with embryonic stem cells. The major limitation to their use, however, is the fact that adult stem cells are exceedingly rare in most tissues. This fact makes identifying and isolating these cells problematic; bone marrow being perhaps the only notable exception. Unlike the case of HSCs, there are as yet no rigorous criteria for characterizing MSCs. Changing acuity about the pluripotency of MSCs in recent studies has expanded their potential application; however, the underlying molecular pathways which impart the features distinctive to MSCs remain elusive. Furthermore, the sparse in vivo distribution of these cells imposes a clear limitation to their study in vitro. Also, when MSCs are cultured in vitro, there is a loss of the in vivo microenvironment, resulting in a progressive decline in proliferation potential and multipotentiality. This is further exacerbated with increased passage numbers in culture, characterized by the onset of senescence related changes. As a consequence, it is necessary to establish protocols for generating large numbers of MSCs but without affecting their differentiation potential. MSCs are capable of differentiating into mesenchymal tissue lineages, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Recent findings indicate that adult bone marrow may also contain cells that can differentiate into the mature, nonhematopoietic cells of a number of tissues, including cells of the liver, kidney, lung, skin, gastrointestinal tract, and myocytes of heart and skeletal muscle. MSCs can readily be expanded in vitro and can be genetically modified by viral vectors and be induced to differentiate into specific cell lineages by changing the microenvironment–properties which makes these cells ideal vehicles for cellular gene therapy. MSCs can also exert profound immunosuppressive effects via modulation of both cellular and innate immune pathways, and this property allows them to overcome the issue of immune rejection. Despite the many attractive features associated with MSCs, there are still many hurdles to overcome before these cells are readily available for use in clinical applications. The main concern relates to in vivo characterization and identification of MSCs. The lack of a universal biomarker, sparse in vivo distribution, and a steady age related decline in their numbers, makes it an obvious need to decipher the reprogramming pathways and critical molecular players which govern the characteristics unique to MSCs. This book presents a comprehensive insight into the biology of adult stem cells and their utility in current regeneration therapies. The adult stem cell populations reviewed in this book include bone marrow derived MSCs, adipose derived stem cells (ASCs), umbilical cord blood stem cells, and placental stem cells. The features such as MSC circulation and trafficking, neuroprotective properties, and the nurturing roles and differentiation potential of multiple lineages have been discussed in details. In terms of therapeutic applications, the strengths of MSCs have been presented and their roles in disease treatments such as osteoarthritis, Huntington’s disease, periodontal regeneration, and pancreatic islet transplantation have been discussed. An analysis comparing osteoblast differentiation of umbilical cord blood stem cells and MSCs has been reviewed, as has a comparison of human placental stem cells and ASCs, in terms of isolation, identification and therapeutic applications of ASC in bone, cartilage regeneration, as well as myocardial regeneration. It is my sincere hope that this book will update the reader as to the research progress of MSC biology and potential use of these cells in clinical applications. It will be the best reward to all contributors of this book, if their efforts herein may in some way help the readers in any part of their study, research, and career development.

Bolted beam-column moment connections between cold-formed steel members

ABSTRACT Twelve beam-to-column connections between cold-formed steel sections consisting of three beam depths and four connection types were tested in isolation to investigate their behavior based on strength, stiffness and ductility. Resulting moment-rotation curves indicate that the tested connections are efficient moment connections where moment capacities ranged from about 65% to 100% of the connected beam capac-ity. With a moment capacity of greater than 80% of connected beam member capacity, some of the connec-tions can be regarded as full strength connections. Connections also possessed sufficient ductility with rota-tions of 20 mRad at failure although some connections were too ductile with rotations in excess of 30 mRad. Generally, most of the connections possess the strength and ductility to be considered as partial strength con-nections. The ultimate failures of almost all of the connections were due to local buckling of the compression web and flange elements of the beam closest to the connection.

Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells

The molecular mechanism between atherosclerosis formation and periodontal pathogens is not clear although positive correlation between periodontal infections and cardiovascular diseases has been reported. Objective: To determine if atherosclerosis related genes were affected in foam cells during and after its formation by P. gingivalis lipopolysaccharide (LPS) stimulation. Methods: Macrophages from human THP-1 monocytes were treated with oxidized low density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis related genes was assayed by quantitative real time PCR and the protein production of granulocyte-macrophage colony-stimulating factor（GM-CSF）, monocyte chemotactic protein-1 (MCP-1), IL-1β, IL-10 and IL-12 was determined by ELISA. Nuclear translocation of NF-κB P65 was detected by immunocytochemistry and western blot was used to evaluate IKB-α degradation to confirm the NF-κB pathway activation. Results: P. gingivalis LPS stimulated atherosclerosis related gene expression in foam cells and increased oxLDL induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes, and nuclear receptors in macrophages. Transcription of the pro-inflammatory cytokines IL-1β and IL-12 was elevated in response to LPS in both macrophages and foam cells, whereas the anti-inflammatory cytokine IL-10 was not affected. Increased NF-κB pathway activation was also observed in LPS and oxLDL co-stimulated macrophages. Conclusion: P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.

A material model for flexural crack simulation in reinforced concrete elements using ABAQUS

This paper presents a material model to simulate load induced cracking in Reinforced Concrete (RC) elements in ABAQUS finite element package. Two numerical material models are used and combined to simulate complete stress-strain behaviour of concrete under compression and tension including damage properties. Both numerical techniques used in the present material model are capable of developing the stress-strain curves including strain softening regimes only using ultimate compressive strength of concrete, which is easily and practically obtainable for many of the existing RC structures or those to be built. Therefore, the method proposed in this paper is valuable in assessing existing RC structures in the absence of more detailed test results. The numerical models are slightly modified from the original versions to be comparable with the damaged plasticity model used in ABAQUS. The model is validated using different experiment results for RC beam elements presented in the literature. The results indicate a good agreement with load vs. displacement curve and observed crack patterns.

The emerging management services of business transformation management

Business transformations are large-scale organizational change programs that, evidence suggests, are often unsuccessful. Our interest is in identifying the management capabilities required for the successful execution of these projects. We advance a service-oriented view of the enterprise, which suggests that different management services need to be identified and integrated in order to execute business transformation. In order to identify those management services that require integration, we conducted an exploratory empirical study of the demand for management services in US and Asia, and we show that two archetypes of management services exist in business transformation initiatives: transactional and transformational management services. We identify the relevant set of transactional and transformational services and discuss what the demand for these services implies for the execution of business transformations.

Structural reliability prediction of a steel bridge element using Dynamic Object Oriented Bayesian Network (DOOBN)

Different from conventional methods for structural reliability evaluation, such as, first/second-order reliability methods (FORM/SORM) or Monte Carlo simulation based on corresponding limit state functions, a novel approach based on dynamic objective oriented Bayesian network (DOOBN) for prediction of structural reliability of a steel bridge element has been proposed in this paper. The DOOBN approach can effectively model the deterioration processes of a steel bridge element and predict their structural reliability over time. This approach is also able to achieve Bayesian updating with observed information from measurements, monitoring and visual inspection. Moreover, the computational capacity embedded in the approach can be used to facilitate integrated management and maintenance optimization in a bridge system. A steel bridge girder is used to validate the proposed approach. The predicted results are compared with those evaluated by FORM method.

Communication and transformation through collaboration: Rethinking drawing activities in early childhood.

This article is a study of the arts in early childhood as a way of learning, for both children and their teachers. The author suggests that drawing can be a powerful tool for collaborative approaches to pedagogy. When teachers draw with children, pathways of communication can be opened, and the collaborative exercise can trigger processes of transformation for both adult and child. In order to present challenges to more traditional, hands-off pedagogical practices in arts education, this article is an account of reflexive arts pedagogies, and how they can work to improve communication and understandings between adults and children. Within the educational contexts of Australian preschooling and primary schooling, the author examines the process of collaborative drawing, and how this can enable a process of transformation. Her analysis, and the accompanying examples of reflexive practices, combine complementary lenses, socio-cultural and postmodern, that she sees as working in harmony to produce new possibilities, in arts education in particular, and, more broadly, in early childhood education.

Simulation of inplane and out of plane AE source in thin plate

In most materials, short stress waves are generated during the process of plastic deformation, phase transformation, crack formation and crack growth. These phenomena are applied in acoustic emission (AE) for the detection of material defects in a wide spectrum of areas, ranging from nondestructive testing for the detection of materials defects to monitoring of microseismical activity. AE technique is also used for defect source identification and for failure detection. AE waves consist of P waves (primary longitudinal waves), S waves (shear/transverse waves) and Rayleigh (surface) waves as well as reflected and diffracted waves. The propagation of AE waves in various modes has made the determination of source location difficult. In order to use acoustic emission technique for accurate identification of source, an understanding of wave propagation of the AE signals at various locations in a plate structure is essential. Furthermore, an understanding of wave propagation can also assist in sensor location for optimum detection of AE signals along with the characteristics of the source. In real life, as the AE signals radiate from the source it will result in stress waves. Unless the type of stress wave is known, it is very difficult to locate the source when using the classical propagation velocity equations. This paper describes the simulation of AE waves to identify the source location and its characteristics in steel plate as well as the wave modes. The finite element analysis (FEA) is used for the numerical simulation of wave propagation in thin plate. By knowing the type of wave generated, it is possible to apply the appropriate wave equations to determine the location of the source. For a single plate structure, the results show that the simulation algorithm is effective to simulate different stress waves.

Investigation of hybridized polyurethane, glass fibre reinforced cement and steel laminate in structural floor plate systems

Sandwich components have emerged as light weight, efficient, economical, recyclable and reusable building systems which provide an alternative to both stiffened steel and reinforced concrete. These components are made of composite materials in which two metal face plates or Glassfibre Reinforced Cement (GRC) layers are bonded and form a sandwich with light weight compact polyurethane (PU) elastomer core. Existing examples of product applications are light weight sandwich panels for walls and roofs, Sandwich Plate System (SPS) for stadia, arena terraces, naval construction and bridges and Domeshell structures for dome type structures. Limited research has been conducted to investigate performance characteristics and applicability of sandwich or hybrid materials as structural flooring systems. Performance characteristics of Hybrid Floor Plate Systems comprising GRC, PU and Steel have not been adequately investigated and quantified. Therefore there is very little knowledge and design guidance for their application in commercial and residential buildings. This research investigates performance characteristics steel, PU and GRC in Hybrid Floor Plate Systems (HFPS) and develops a new floor system with appropriate design guide lines.

Inter-sector leader transitions and organisation transformation : a research agenda

Faced with the need for strategic change, structural and cultural realignment, innovation and value-adding, many public sector organisations are tapping into a wider senior leadership talent pool and attracting successful leaders from other sectors (Flynn and Thompson, 2009). Leadership renewal has resulted, in some cases, in the external recruitment of whole senior leadership teams (Hockridge, 2008), raising issues about the influence of context on leader success (Pawar and Eastman, 1997) and potential leader transition failure, a costly outcome for leaders and organisations (Howard, 2001). There is little research on inter-sector leader transitions, which is surprising given the significant costs associated with leader acquisition and failure(Conger, 2010; Day and Halpin, 2004). For example, it is not clear what organizations do (or do not do) to ensure the outcomes of their significant investment in inter sector transitions are realised. In addition, it is not clear how the individual leader manages the challenging transition into a new leadership context and how their approach to leadership facilitates or inhibits successful transition (Avolio, 2010). Leader assimilation programs have been developed to assimilate new leaders (Manderscheid, 2008); however, assimilation is not necessarily a desired organisational outcome (Denis and Pineault, 2000). In this paper we critically review the limited literature on inter-sector leader transitions and transformational change outcomes and argue for a mutual accommodation approach. We draw on our own initial empirical work to propose the elements of a program for achieving this outcome from the perspective of the public organisation and the inter-sector appointee.

Wind uplift strength of trapezoidal steel cladding with closely spaced ribs

When crest-fixed thin trapezoidal steel cladding with closely spaced ribs is subjected to wind uplift/suction forces, local dimpling or pull-through failures occur prematurely at their screw connections because of the large stress concentrations in the cladding under the screw heads. Currently, the design of crest-fixed profiled steel cladding is mainly based on time consuming and expensive laboratory tests due to the lack of adequate design rules. In this research, a shell finite element model of crest-fixed trapezoidal steel cladding with closely spaced ribs was developed and validated using experimental results. The finite element model included a recently developed splitting criterion and other advanced features including geometric imperfections, buckling effects, contact modelling and hyperelastic behaviour of neoprene washers, and was used in a detailed parametric study to develop suitable design formulae for local failures. This paper presents the details of the finite element analyses, large scale experiments and their results including the new wind uplift design strength formulae for trapezoidal steel cladding with closely spaced ribs. The new design formulae can be used to achieve both safe and optimised solutions.