Mesenchymal stromal cells and the innate immune response

AbstractMesenchymal stromal cells (MSC) have been exploited for their immunomodulatory properties in the treatment of a number of immune-based disorders, including Graft versus Host Disease (GvHD) and type 1 diabetes. The mechanisms for inducing therapeutic effect still remain largely unknown however, with research focused on understanding how MSCs interact with individual immune cell subsets. Within this review we address what is known about the interactions of MSCs with cells of the innate immune system, how they respond to their microenvironment and how this relates to therapeutic effects we see both within in vivo animal models and in clinical trials

Oral mucosal progenitor cell clones resist In Vitro myogenic differentiation

Abstract Progenitor cells derived from the oral mucosa lamina propria (OMLP-PCs) demonstrate an ability to differentiate into tissue lineages removed from their anatomical origin. This clonally derived population of neural-crest cells have demonstrated potential to differentiate along mesenchymal and neuronal cell lineages. Objective Significant efforts are being made to generate functioning muscle constructs for use in research and clinical tissue engineering. In this study we aimed to determine the myogenic properties of clonal populations of expanded OMLP-PCs. Design PCs were subject to several in vitro culture conditions in an attempt to drive myogenic conversion. Methodologies include use of demethylation gene-modifying reagents, mechanical conditioning of tissue culture substrates, tuneable polyacrylamide gels and a 3-dimensional construct as well as published myogenic media compositions. PCR and immunostaining for the muscle cell markers Desmin and MyoD1 were used to assess muscle differentiation

Adult teaching and learning theory: a psychoanalytic investigation

The overarching aim of this thesis is to enhance the theoretical status of post-compulsory education by effecting a non-empirical, psychoanalytic examination of adult teaching and learning theories. The study arises out of the observation that – in comparison with disciplines within the Social Sciences, Arts and Humanities - psychoanalytic perspectives are both underemployed in practical contexts and have negligible theoretical impact within this field. The study provides a contribution to educational theory and practice through the development of a postmodern psychoanalytical methodology and its methods. These are operationalised through the development of a suite of tools based on Jung's (1971) the theory of psychological types. This involves the adaptation of Jung's psychological categories into epistemological characteristics that are then used to identify strengths, contradictions and omissions within theoretical material. The resulting Jungian Typological Instrument (JTI) is applied to selected case study topics that reflect contemporary discourses, theories and concepts within the field of adult teaching and learning. In order to demonstrate the effectiveness of the JTI it is applied to two case study topics and critically examines their theoretical underpinnings. The first of these topics is the 'micro' model of reflection-in-action, which is drawn from Schön's (1983) formulation of reflective practice. The larger, 'macro', discourse of lifelong learning forms the second case study as articulated in the UNESCO report Learning to Be (Faure et al. 1972) and the Green Paper The Learning Age (DfEE 1998). The insights and outcomes arising from these analyses form the evaluation process for the methods. As psychoanalytic approaches are not unproblematic, this investigation incorporates philosophical reflection and conceptual analysis as meta-level evaluation strategies for the methodological level of the study. This dual-level evaluation reveals that the proposed methodology and methods together offer a robust and trustworthy approach to theoretical analysis, which has potential applications for both theory and practice within the adult teaching and learning context

Early Settlement in European Merger Control

We analyse the determinants of early settlement between merging parties and the European Commission over remedies that remove concerns of anticompetitive effects. This extends the previously narrow range of econometric literature on early settlement. Consistent with the theory of early settlement, our results confirm the importance of delay costs and of uncertainty, measured by the complexity of the economic analysis required for each merger. We also find a non-monotonic effect of agency resourcing, which raises questions about the Commission's efficiency in times of high case load. Econometrically, we select a sample of merger decisions in which the European Commission intervened due to concerns of anticompetitive effects, and our selection model provides estimates of the factors determining intervention by the Commission. Conclusions are drawn for public policy

Novel strategies for enhancing tissue integration in cartilage repair.

Articular cartilage is found on the surface of opposing long bones within the synovial joint and aids to dissipate loads. Adult cartilage lacks the ability to initiate a repair response when injured due to its aneural and avascular nature. Surgical techniques have been developed to enhance this repair process but none to date rival that of natural cartilage. Repair tissue is often of a fibrocartilaginous nature which does not have the biomechanical stability of articular cartilage. Integration between newly synthesised tissue and the endogenous cartilage is invariably poor as well, leading to degeneration of the repair tissue and surrounding cartilage with time. The aim of this study was to develop strategies for the enhancement of integration between new and pre-existing articular cartilage to form a more biomechanically stable repair tissue. The migratory capacities of chondrocytes isolated from young and mature articular cartilage have been investigated using a Boyden chamber system, as well as the effects of different matrix substrates and chemoattractants on this process. Using this system the substrate dependent chemotactic effects of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGFbeta1) were only seen if the cells were seeded onto a fibronectin substrate. The inhibitory effect of chondroitin sulphate (CS) chains on chondrocyte migration was also demonstrated. Further experiments using an in vitro model of cartilage injury confirmed this, as it was demonstrated that chondrocytes migrated into chondroitinase ABC treated cartilage but not into untreated controls. Biosynthesis studies were used to demonstrate the anabolic effects of IGF-1 and TGFpi on chondrocytes. Radiolabelled sulphate and proline were used as a measure of sulphated glycosaminoglycan and collagen biosynthesis respectively. These experiments demonstrated increased biosynthesis of both matrix molecules by chondrocytes from both age groups in response to these growth factors. In addition, these results suggest that the newly synthesised molecules were assembled into an extracellular matrix by the cells. The results from both the migration and biosynthesis experiments demonstrated the potential of IGF-1 and TGFbeta1 for enhancing cartilage repair, but also illustrated the limitations of their short half lives. Constructs encoding the mature peptides of IGF-1 and TGFbeta1 were therefore developed for transfection into chondrocytes. The ability of these transfected cells to migrate was investigated on a chondroitinase ABC treated aggrecan substrate. Here a constant trend of increased migration with the transfected cells was seen when compared to controls. This study demonstrates the ability of chondrocytes from both young and mature articular cartilage to migrate. This is the first study to report this using skeletally mature articular cartilage. In addition, the inhibitory effects of CS chains in chondrocyte migration have been shown using both the Boyden chamber system and an in vitro model of cartilage injury. The over-expression of IGF-1 and TGFbeta1 in articular chondrocytes demonstrated the possibility of increasing both the migration of cells into articular cartilage as well as up- regulating their capacity for matrix biosynthesis, thereby creating an integrated repair tissue improving on current repair strategies

An assessment of a portable cyanoacrylate fuming system (LumiFume™) for the development of latent fingermarks

The effectiveness and suitability of a portable cyanoacrylate fuming system (LumiFume™) with Lumicyano™ at detecting latent fingermarks was assessed. The first phase of the study compared the LumiFume™ system with traditional cabinet fuming and black/white powder suspension for the development of latent fingermarks on a variety of surfaces (glass, plastic bin bag, laminated wood and tile) by means of depletion series’ from 10 donors and four ageing periods (1, 7, 14 and 28 days). The portable fuming system provided superior quality of developed marks on glass and laminated wood whereas powder suspension was better on bin bags and all three techniques were comparable on tile. A decrease in mark quality was recorded from 1-14 days for the fuming techniques before an increase at 28 days. Lumicyano™ fluorescence stability studies over a 28 day period by means of depletion series’ on glass slides and plastic bin bags revealed better quality marks for the portable system LumiFume™; however, storing marks under light conditions expedited deterioration for both systems. All marks developed with Lumicyano™ were subsequently treated with BY40 resulting in further improvement in mark quality for all substrates and ageing periods, with the exception of laminated wood which absorbed the fluorescent stain reducing the contrast in the process. The second phase of the study consisted of a pseudo-operational trial on 300 various substrates (e.g. glass bottles, aluminium cans, plastic bags) recovered from recycling bins. LumiFume™ and Lumicyano™ yielded 1,469 marks whereas Lumicyano™ cabinet fuming and powder suspension yielded 1,026 and 641 marks respectively. Similar to the first phase of the study, further treatment of the Lumicyano™ treated marks with BY40 resulted in further quality improvement as well as additional new marks. The LumiFume™ system produced results at least equivalent to the traditional cabinet fuming with Lumicyano™ highlighting its potential for implementation into casework to process crime scenes

Magic Polygons and Their Properties

Magic squares are arrangements of natural numbers into square arrays, where the sum of each row, each column, and both diagonals is the same. In this paper, the concept of a magic square with 3 rows and 3 columns is generalized to define magic polygons. Furthermore, this paper will examine the existence of magic polygons, along with several other properties inherent to magic polygons.Comment: 7 pages, 4 figure