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Ireland is distinguished by the high degree of openness of its labour market and the importance of foreign direct investment (FDI) in the economy. We develop a neo-classical growth model to explore the consequence of these characteristics for the response of an economy to the kinds of shocks that are widely recognised to have been of importance in driving the Irish boom.

An important determinant of a region's attractiveness to foreign investors is its rate of corporation tax. Besides stimulating real economic activity, low corporation tax rates also induce multinational corporations to shift profits into the jurisdiction, frequently through the manipulation of transfer prices. This practice can lead to a substantial distortion of output figures. Since national or sectoral R&D intensities are usually measured relative to output, transfer pricing also therefore distorts these measurements. The present paper proposes a simple alternative measure of R&D intensity. Implementation on Irish data shows that the two approaches yield substantially different results.

There is a large literature on the positive spillovers frequently thought to be associated with inward foreign direct investment. Aitken et al. (1996) identify several cases, however, where inward FDI appears to have reduced wages in domestic firms. They suggest that this might arise either because foreign firms increase the degree of product‐market competition that domestic firms face, or because they poach the best workers from domestic firms. We concentrate on the second effect, arguing that the first is unlikely to arise in the Irish case to which our data pertain. In a theoretical section we show that the labour‐market poaching effect cannot generate the results postulated if labour markets are competitive and production functions are of the Cobb–Douglas variety, but that it can arise if production functions display higher elasticities of substitution. In an empirical section based on a sample of larger Irish firms we show that, consistent with our theoretical model, foreign presence has different ef...

The CEEC share of Irish exports has grown fivefold since transition began, with export sales expanding in all sectors. Even at current income levels there remains scope for a further doubling of exports, and trade will grow even more substantially if accession facilitates the CEEC in converging more rapidly on EU living standards. Most analyses predict that the EU15 sectors that face the greatest threats of enlargement-induced disruption are Food and Textiles, Clothing and Footwear. In the case of Irish Food Processing, however, the prognosis of the present paper is positive since Irish agricultural output differs quite strongly from that of the CEE economies. The adjustment costs associated with industrial dispution, furthermore, are highest in economies with rigid labour markets, whereas the flexibility of the Irish labour market seems to have improved substantially over the last decade or so. Outward FDI from Ireland has grown strongly over the Celtic Tiger era, and Irish multinational firms have been reasonably active in acquiring companies in their sectors in Cental and Eastern Europe. The main worry for Ireland is that the more successful accession states may divert FDI inflows away from Ireland. Micro-level analysis of the conditions pertaining in some of Ireland's most important foreign-dominated sectors – information technology, pharma-chem and instrument engineering – suggests that these threats may be overstated. The leading CEE economies, rather than drawing FDI away from Ireland, may instead contribute to the further development of EU-wide production networks, making the networks themselves more competitive as global players. The net cost to Ireland of agreements already reached on the financing of enlargement is quite manageable. The cost to Ireland would escalate dramatically, however, if costs and benefits were to be redistributed within the EU in line with current income levels, entailing a substantial transformation of the CAP transfer mechanism.

The information technology sector in Europe, comprising the production of computer hardware and software, is disproportionately located on the continent's western periphery. The vast bulk of computers sold in Europe in the 1990s were assembled either in Ireland or Scotland, while Ireland also accounted for over 40 per cent of all packaged software and 60 per cent of all business software sold in Europe. As the sector in both these locations is largely foreign owned, the question arises as to whether EU enlargement might impact on the geography of the sector by diverting information technology FDI from the western to the new eastern periphery. This issue is explored in the present paper by analysis of five individual sub-segments: computer assembly and electronic components, R&D, mass-market packaged software and the remainder of the software sector. The paper deems it likely that computer assembly operations will continue the shift seen in recent years from Ireland and Scotland to Central and Eastern Europe. The production of electronic components such as microchips represents a growing share of activity in most EU locations as well as in the CEE countries. Analysis suggests that this pattern of geographically-dispersed growth will resume once the consequences of the collapse of the high-tech bubble are played out. The distribution of R&D activity across Europe and globally is also considered unlikely to be much affected by enlargement. As for software, as long as localisation activities remain important, Ireland – the EU location in which most of this activity is carried out – seems set to be able to compete strongly, given the attractiveness of its English-language environment and other attributes to the young continental Europeans upon which this activity relies. Most software services remain largely non-tradable however. This sector will grow in the accession states as computer penetration rates converge on the EU average, but without displacing activity from the incumbent EU member states. For firms already competing in the tradable niche software segment, on the other hand, enlargement cannot but be beneficial because of its impact on the size of the market into which they sell.

Enlargement will have important implications for Portugal. To some extent these are already noticeable in the wake of the Europe Agreements. Portuguese exports bear a strong similarity to those from Central and Eastern Europe and have been losing EU market share as the CEE economies expand. To this extent Portugal can be said to be ‘being squeezed from below’ in that its traditional export sectors face greater competition. At the same time, its specialisation seems to be increasingly confined to low-technology, low-added-value sectors with declining demand, as strong FDI inflows to the CEEC lead to an increasing preponderance of more dynamic sectors in their export structures. Thus, it is also being squeezed from above. This suggests that there may be substantial industrial disruption, in response to which labour market flexibility and dynamic entrepreneurial response is crucial. A worrying aspect of this is that intersectoral mobility is generally easier the more highly educated the workforce – an indicator on which Portugal scores quite poorly. Nevertheless, it is worthwhile mentioning that the Portuguese labour market displays a high degree of flexibility, consistent with its low unemployment rate of recent decades (Bover and Portugal, 2000). This will help to minimise the adjustment costs associated with increased competition from the accession states. he present paper is a broad reflection on the economic impact of Eastern enlargement on the Portuguese economy. Section 2 deals with external trade; Section 3 with inward FDI; Section 4 with migration flows and Section 5 with the Structural and Cohesion Fund programmes. Section 6 concludes. info:eu-repo/semantics/publishedVersion

This paper sets out to analyse the effect of plant and sectoral level characteristics on the provision of training to employees using plant level data for Irish manufacturing. There is no clear evidence that foreign owned plants are more likely to provide training. By contrast, we find that they spend less than domestic plants on training, ceteris paribus. There is also no evidence that plants that receive training grants are more likely to provide training. This may be likely to reflect the targeting of training grants on plants that are otherwise unlikely to provide much training. We do, however, find that training activity in the sector, either by other foreign or domestic plants, has a positive effect on plant level training activity, at least for domestic owned plants.

Previous studies have shown that the localisation of firms can be an important factor in attracting new foreign direct investment into a host country. The authors distinguish between “efficiency agglomerations” which arise as firms increase their efficiency by locating close to each other, and “demonstration effects” whereby existing firms send signals to new investors as to the reliability and attractiveness of the host country. They try to disentangle these two effects by examining the location of US firms in Ireland. They find that both sources of agglomerations have been important determinants of US firm entry into Ireland. JEL no. F23

Objective To explore the role that implanted mesenchymal stem cells may play in tissue repair or regeneration of the injured joint, by delivery of an autologous preparation of stem cells to caprine knee joints following induction of osteoarthritis (OA). Methods Adult stem cells were isolated from caprine bone marrow, expanded in culture, and transduced to express green fluorescent protein. OA was induced unilaterally in the knee joint of donor animals by complete excision of the medial meniscus and resection of the anterior cruciate ligament. After 6 weeks, a single dose of 10 million autologous cells suspended in a dilute solution of sodium hyaluronan was delivered to the injured knee by direct intraarticular injection. Control animals received sodium hyaluronan alone. Results In cell-treated joints, there was evidence of marked regeneration of the medial meniscus, and implanted cells were detected in the newly formed tissue. Degeneration of the articular cartilage, osteophytic remodeling, and subchondral sclerosis were reduced in cell-treated joints compared with joints treated with vehicle alone without cells. There was no evidence of repair of the ligament in any of the joints. Conclusion Local delivery of adult mesenchymal stem cells to injured joints stimulates regeneration of meniscal tissue and retards the progressive destruction normally seen in this model of OA.

This article compares the economic performance of the EU cohesion countries ‐ Greece, Spain, Portugal and Ireland ‐ from 1960 to the present, in order to identify the processes that have promoted or inhibited real convergence prospects at various points in time. The likely impacts of EMU in strengthening or weakening these processes are then analysed. Amongst the factors studied are labour-market performance, macroeconomic stability and the efficacy of microeconomic policy-making.

B ARRY F., G oRG H. and M CDOWELL A. (2003) Outward FDI and the investment development path of a late-industrializing economy: evidence from Ireland, Reg. Studies 37 , 341-349. The Investment Development Path (IDP) hypothesis holds that a country's net outward direct investment position is systematically related to its level of economic development. Ireland is an interesting test case because of the importance of inward foreign direct investment (FDI) over the last three decades and the recent increase in outward FDI by Irish-owned multinationals. We find empirical support for the IDP concept for the Irish case. Our sectoral analysis suggests that Ireland's outward FDI flows are disproportionately horizontal and oriented towards non-internationally-tradable sectors. Also, the firm-specific assets of Irish multinationals lie neither in R&D nor in the type of product differentiation associated with high advertising expenditures. B ARRY F., G oRG H. et M CDOWELL A. (2003) L'investissement direct a l'etranger...

This paper presents a dynamic general equilibrium analysis of the hypothesis that fiscal spending reductions may be expansionary. The impact of balanced budget fiscal spending on output in this model is normally negative. Quantitatively, these effects can be large. Moreover, the effects are distinctly non-linear; the higher is the initial fiscal spending to GDP ratio, the greater the expansionary impact of fiscal spending cuts. Nevertheless, the effects are likely to be accrued only gradually, so that fiscal contraction does not lead to large immediate increases in output. The analysis is extended to an economy with unemployment, and to an open economy. Some discussion of the empirical relevance of the hypothesis is presented.

This paper analyses the role of the Irish tax regime in the country’s economic development. Corporation tax rates had been amongst the lowest in Europe for decades, leading to a strong FDI presence in the economy. The coincidence of the introduction of the Single European Market and the US-led high-tech boom fuelled high-tech FDI inflows into (and within) the EU over the 1990s. and Ireland captured a substantially-increased share of these inflows. This was an important contributory factor to the economic boom of the decade, which saw the country come to be dubbed the “Celtic Tiger economy”. The country’s competitiveness was further enhanced by developments on the income-tax front over this period.

This paper draws out lessons from Ireland´s economic experience over the course of EU membership. The author starts with a description of the effects of opening up to free trade, and highlights the problems of the 1970s and 1980s that arose as a consequence of misguided fiscal policy. He then turns to the beneficial developments that paved the way to the emergence of the Celtic Tiger economy. EU aid alone, he argues, cannot guarantee convergence. It is likely to be of greatest benefit when the other conditions for real convergence including a well-functioning labour market, reform-oriented microeconomic policy and macroeconomic stability ? are also in place. For countries attempting to follow the Irish strategy of attracting inward FDI in high-tech manufacturing sectors, the author emphasises that low corporation-tax rates are only one part of the story. A supportive public administration system and an abundance of human capital of the appropriate type are also key requirements.

Background: Rodent mesenchymal stem/stromal cells (MSCs) enhance repair after ventilator-induced lung injury (VILI). We wished to determine the therapeutic potential of human MSCs (hMSCs) in repairing the rodent lung. Methods: In series 1, anesthetized rats underwent VILI (series 1A, n = 8 to 9 per group) or protective ventilation (series 1B, n = 4 per group). After VILI, they were randomized to intravenous administration of (1) vehicle (phosphate-buffered saline); (2) fibroblasts (1 × 107 cells/kg); or (3) human MSCs (1 × 107 cells/kg) and the effect on restoration of lung function and structure assessed. In series 2, the efficacy of hMSC doses of 1, 2, 5, and 10 million/kg was examined (n = 8 per group). Series 3 compared the efficacy of both intratracheal and intraperitoneal hMSC administration to intravascular delivery (n = 5–10 per group). Series 4 examined the efficacy of delayed hMSC administration (n = 8 per group). Results: Human MSC’s enhanced lung repair, restoring oxygenation (131 ± 19 vs. 103 ± 11 vs. 95 ± 11 mmHg, P = 0.004) compared to vehicle or fibroblast therapy, respectively. hMSCs improved lung compliance, reducing alveolar edema, and restoring lung architecture. hMSCs attenuated lung inflammation, decreasing alveolar cellular infiltration, and decreasing cytokine-induced neutrophil chemoattractant-1 and interleukin-6 while increasing keratinocyte growth factor concentrations. The lowest effective hMSC dose was 2 × 106 hMSC/kg. Intraperitoneal hMSC delivery was less effective than intratracheal or intravenous hMSC. hMSCs enhanced lung repair when administered at later time points after VILI. Conclusions: hMSC therapy demonstrates therapeutic potential in enhancing recovery after VILI.

A model of a small open economy with open capital and labour markets is presented. Labour demand is based on capital mobility and increasing returns in production. Migration decisions are based on the relative attractiveness of regions in terms of the stock of infrastructure, including its tax cost and the degree of congestion, and the level of wages prevailing. Equilibria are not Pareto efficient because individuals do not take account of the impact of their actions on the level of wages prevailing, the extent of the tax base to finance infrastructural provision, or the degree of congestion. The model generates new insights into a range of policy issues that surfaced over the course of the recent Irish boom.

Objective Mesenchymal stem cells (MSCs) are resident in the bone marrow throughout normal adult life and have the capacity to differentiate along a number of connective tissue pathways, among them bone, cartilage, and fat. To determine whether functionally normal MSC populations may be isolated from patients with advanced osteoarthritis (OA), we have compared cells from patients undergoing joint replacement with cells from normal donors. Cell populations were compared in terms of yield, proliferation, and capacity to differentiate. Methods MSCs were prepared from bone marrow aspirates obtained from the iliac crest or from the tibia/femur during joint surgery. In vitro chondrogenic activity was measured as glycosaminoglycan and type II collagen deposition in pellet cultures. Adipogenic activity was measured as the accumulation of Nile Red O-positive lipid vacuoles, and osteogenic activity was measured as calcium deposition and by von Kossa staining. Results Patient-derived MSCs formed colonies in primary culture that were characteristically spindle-shaped with normal morphology. The primary cell yield in 36 of 38 cell cultures from OA donors fell within the range found in cultures from normal donors. However, the proliferative capacity of patient-derived MSCs was significantly reduced. There was a significant reduction in in vitro chondrogenic and adipogenic activity in cultures of patient-derived cells compared with that in normal cultures. There was no significant difference in in vitro osteogenic activity. There was no decline in chondrogenic potential with age in cells obtained from individuals with no evidence of OA. Conclusion These results raise the possibility that the increase in bone density and loss of cartilage that are characteristic of OA may result from changes in the differentiation profile of the progenitor cells that contribute to the homeostatic maintenance of these tissues.

Cellular therapy involves the isolation, expansion, and transplantation of human cells for the replacement or regeneration of injured tissues. It is one of the most significant tissue repair strategies in the emerging discipline of regenerative medicine. Cellular strategies have been applied in joint repair for the treatment of acute cartilage injury, meniscal repair, and osteoarthritis (OA). Many of these efforts have been motivated by the apparent incapacity of cartilage to repair itself and the observation that initial trauma is likely to lead to sustained joint degeneration. A particularly important question that arises about cellular therapy in OA relates to the long-term outcome of these procedures. In addition, questions remain about the most suitable cell source, the advantages of allogeneic over autologous therapy, their potential uses in late stage OA, and, not least, the logistics of manufacturing and supply. These topics are discussed in this review, as well as an evaluation of knowledge gaps and technical obstacles that remain to be addressed.

Recently, it has been shown that mesenchymal stem cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen and are able to inhibit proliferation of MHC-mismatched stimulated lymphocytes, enabling their use as in vivo allogeneic transplants. However, prior to clinical application of allo-MSCs, in vitro tests are required to confirm the safety of treatment protocols.To evaluate the immunosuppressive capabilities of equine bone-marrow-derived MSCs (BM-MSCs) on MHC-mismatched lymphocytes.In vitro experiment.Phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) from 3 Thoroughbreds (recipients) were co-cultured with mismatched BM-MSCs from 3 Connemara ponies (donors). Proliferation of lymphocytes was monitored by carboxyfluorescein succinimidyl ester labelling and analysed by flow cytometry. In total, 6 horses were haplotyped using microsatellites to confirm mismatching. Optimisation of the conditions to stimulate Thoroughbred lymphocytes and titration of equine anti-CD4 and anti-CD8 antibodies were performed. Connemara pony and Thoroughbred BM-MSCs were isolated, expanded and characterised by tri-lineage differentiation. Finally, BM-MSCs from both breeds were set up in co-culture at different ratios with stimulated Thoroughbred lymphocytes. Proliferation of CD4(+) and CD8(+) cells was determined by flow cytometry.A high proportion of CD4/CD8 double-positive lymphocytes were found in freshly isolated PBMCs, although this percentage decreased after 4 days of culture. Mismatched BM-MSCs inhibited proliferation of stimulated lymphocytes in a dose-dependent manner, with the greatest suppression occurring at a 1:10 ratio of BM-MSCs to PBMCs. Proliferation of CD4(+) and CD8(+) subpopulations decreased in 1:10 co-culture, with statistical significance in the case of CD8(+) cells, while that of the CD4/CD8 double-positive population was similar to the phytohaemagglutinin control.The results demonstrate dose-dependent immunosuppression of stimulated lymphocytes by mismatched equine BM-MSCs, supporting their future application in allo-MSC clinical treatments.

Key termsequine; immunophenotype; ISCTmarkersThere has been growing interest in recent years in the use ofmesenchymal stem cells (MSCs) as a potential treatment fora number of important diseases. MSCs were first describedas colony-forming units consisting of fibroblast-like cellsderived from bone marrow (1). Since then they have beenisolated from many different tissues such as adipose, muscle,synovium, dental pulp, tendon, peripheral blood, Wharton’sjelly, and umbilical cord blood (2–4). The biological charac-teristics of MSCs that contribute to their therapeutic activityand the mechanisms of action continue to be studied.Despite many advances in MSC therapy, a specific markerthat defines cultured MSCs and identifies them within theirtissue niche has remained elusive. As a consequence, theInternational Society of Cell Therapy (ISCT) proposed a setof minimal test criteria for human MSCs as a first attempt atstandardization for laboratory and preclinical research. Thesecriteria include plastic adherence, trilineage differentiation toosteoblast, adipocyte, and chondrocyte lineages, and a phe-notype relating to surface marker expression. This latter stip-ulates that MSCs, measured by flow cytometry, must show 95% positivity for CD73, CD90, and CD105 antigens and 2% for CD45, CD34, CD14 or CD11b, CD79a or CD19,and HLA class II (5).These criteria were established only for human MSCresearch. However, the study of MSCs is not limited to humanapplications: many animal models are routinely used in pre-clinical investigation and in veterinary applications. There isan urgent need for a universal marker(s) to define and identifyMSCs from all tissues of origin, which will apply across allspecies.There has been an interest in equine MSC therapy formore than 10 years, especially in the treatment of musculo-skeletal disorders such as tendon or joint disease. In addition,because of similarities in terms of structure and biomechanics,the horse is accepted by the US Food and Drug Administra-tion as an animal model suitable for the investigation of carti-lage and tendon repair therapies for human use. In recentyears, several equine trials have been carried out using MSCsfrom different sources. Most of these reported a positive out-come (6) although the mechanism of action remains unclear.It can be argued that failure to understand the biologicalmechanism of repair hinders development of optimized thera-pies. It can also be argued that the lack of meaningful potencytests will hamper the development of standardized cell prepa-rations. The most important identifying characteristics ofequine MSCs have been plastic adhesion and trilineage poten-tial. The use of cell surface markers has been limited due tothe lack of commercial antibodies that cross-react with equineantigens (7).The paper published in this issue (p. XXX) by Paebstet al. is the first to analyze the complete panel of human MSCmarkers established by the ISCT in equine MSCs derived fromfive different tissue sources (marrow, adipose, tendon, umbili-cal cord tissue, and umbilical cord blood).

Despite the fact, that a range of clinically viable imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), photo emission tomography (PET), ultrasound and bioluminescence imaging are being optimised to track cells in vivo, many of these techniques are subject to limitations such as the levels of contrast agent required, toxic effects of radiotracers, photo attenuation of tissue and backscatter. With the advent of nanotechnology, nanoprobes are leading the charge to overcome these limitations. In particular, single wall nanotubes (SWNT) have been shown to be taken up by cells and as such are effective nanoprobes for cell imaging. Consequently, the main aim of this research is to employ mesenchymal stem cells (MSC) containing SWNT nanoprobes to image cell distribution in a 3D scaffold for cartilage repair. To this end, MSC were cultured in the presence of 32μg/ml SWNT in cell culture medium (αMEM, 10% FBS, 1% penicillin/streptomycin) for 24 hours. Upon confirmation of cell viability, the MSC containing SWNT were encapsulated in hyaluronic acid gels and loaded on polylactic acid polycaprolactone scaffolds. After 28 days in complete chondrogenic medium, with medium changes every 2 days, chondrogenesis was confirmed by the presence of glycosaminoglycan. Moreover, using photothermal optical coherence tomography (PT-OCT), the cells were seen to be distributed through the scaffold with high resolution. In summary, these data reveal that MSC containing SWNT nanoprobes in combination with PT-OCT offer an exciting opportunity for stem cell tracking in vitro for assessing seeding scaffolds and in vivo for determining biodistribution.

This is a study of three models of partnership between Trinity College Dublin and higher education institutes in six African countries. The goal is to deliver collaborative doctoral training programmes in global health, natural sciences and economics, to train researchers and build research and teaching capacity in African institutions, which is increasingly seen as a key influence on economic development. The purpose of this study was to assess the three models employed in order to understand their strengths and weaknesses, capture lessons from our partnerships and make recommendations to others establishing North-South doctoral training programmes. Findings from qualitative interviews revealed strengths, weaknesses, opportunities and threats for each model, and the specific strengths, challenges, recommendations and implications for future programme improvements are highlighted and discussed.

Objective TSG-6 [the product of tumor necrosis factor (TNF)-stimulated gene-6] is a hyaluronan-binding protein that is present in the synovial fluids of arthritis patients and is secreted by cells of articular joints (e.g. chondrocytes and synoviocytes). This study examines the pattern of TSG-6 expression in normal and diseased cartilage and synovium using immunohistochemical techniques. Design A polyclonal antibody was raised against recombinant Link module from human TSG-6 and used to detect the protein in tissue sections taken from osteoarthritis (OA) and rheumatoid arthritis (RA) patients and controls. Results There was no TSG-6 detected in normal tissues. In all OA synovium there was intense TSG-6 expression throughout the intimal layer, whereas in RA staining in this region was generally less pronounced and was absent at the synovial surface in tissues exhibiting significant inflammation. In RA TSG-6 was also expressed by infiltrating leukocytes and by cells at the cartilage–synovium pannus junction. TSG-6 immunoreactivity was present in the tunica intima of blood vessels in OA subintima, being particularly noticeable in the thickened smooth muscle of inflamed vessel walls, but was mostly confined to the lumen of the vessel in RA. In cartilage the majority of chondrocytes expressed TSG-6 in both OA and RA, usually with extensive staining in the surrounding matrix. Conclusion TSG-6 is present within synovium and cartilage of arthritic joints, but not normal controls, and is synthesized by the resident cells. The pattern of TSG-6 expression is consistent with its proposed roles in extracellular matrix (ECM) remodeling and cellular proliferation.

Despite the immunosuppressive, homing, and regenerative capabilities of mesenchymal stem cells (MSCs), their ability to migrate to arthritic joints and influence the course of arthritis in vivo remains poorly understood. The objective of this study was to determine if allogeneic MSCs migrate to inflamed joints in vivo and to determine if MSCs expressing the costimulation blocker cytotoxic T lymphocyte associated antigen-4 coupled to immunoglobulin-G (CTLA4Ig) could be used to ameliorate collagen induced arthritis (CIA). The migration of systemically delivered inbred mouse strain (FVB) MSCs to migrate to inflamed joints in CIA was studied using real-time quantitative polymerase chain reaction. Furthermore, the effect of BALB/c MSCs modified with an adenoviral vector to express CTLA4Ig, on T cell function in vitro and on CIA in vivo was assessed. After systemic delivery of FVB MSCs, eGFP DNA was detectable in the joints of mice with CIA confirming that some MSCs had reached to inflamed joints. BALB/c MSCs suppressed the secretion of both TNFα and IFNγ, and reduced the ratio of Th1:Th2 cytokine expression, by DBA/1 T cells in vitro irrespective of viral modification. The expression of CTLA4Ig did not augment this effect. Despite a worsening of disease scores after infusion of BALB/c MSCs in vivo, BALB/c MSCs expressing CTLA4Ig significantly delayed the onset of inflammatory arthritis in CIA. These data demonstrate that allogeneic MSCs can migrate to the inflamed joints of CIA in vivo and that genetically modified allogeneic MSCs may be considered for development of gene therapy strategies for inflammatory arthritis.

For over 70 years Irish income per head remained at around 60 percent of the level prevailing in the country's dominant trading partner, the UK. Ireland began to converge rapidly over the last 15 years however, and parity has now been achieved with the UK and the overall EU. This paper analyses the changes in public policy that facilitated the turnaround in economic fortunes.

Ireland has been the economic success story of the 1990s. Growth in GNP and in employment has far exceeded those seen elsewhere. We ask first whether this is simply a delayed catching-up process. Even if this turns out to be so, the question remains as to what the key differences in policy were between the unsuccessful phase, from 1950 to 1988, and the phenomenally successful phase since then. We present a brief overview of the key differences in terms familiar from conventional growth theory, and go on to look more carefully at the constellation of factors explaining the precise timing of the turnaround in economic fortunes.

Adult mesenchymal stem cells (MSCs), found in the bone marrow, have the potential to differentiate into multiple connective tissue types, including cartilage. In this study, we examined the potential of a porous gelatin sponge, Gelfoam, for use as a delivery vehicle for MSCs in cartilage regeneration therapy. Adult human MSCs (hMSCs) were seeded throughout the gelatin sponge after a 2-h incubation period. When cultured for 21 days in vitro in a defined medium supplemented with 10 ng/mL of TGF-beta 3, hMSC/Gelfoam constructs produced a cartilage-like extracellular matrix containing sulfated glycosaminoglycans (s-GAGs) and type-II collagen, as evident upon histologic evaluation. Constructs loaded with a cell suspension of 12 x 10(6) cells/mL produced an extracellular matrix containing 21 microg of s-GAG/microg of DNA after 21 days of culture. This production was more efficient than constructs loaded at higher or lower cell densities, indicating that the initial seeding density influences the ability of cells to produce extracellular matrix. When implanted in an osteochondral defect in the rabbit femoral condyle, Gelfoam cylinders were observed to be very biocompatible, with no evidence of immune response or lymphocytic infiltration at the site. Based on these observations we conclude that Gelfoam resorbable gelatin sponge is a promising candidate as a carrier matrix for MSC-based cartilage regeneration therapies.

Early versions of the equilibrium approach to fiscal policy implied that temporary increases in public consumption reduced investment while permanent expansions left it unchanged; currentaccount effects in the open economy were held to be analogous to these closed-economy investment effects. It has been shown recently though that these investment results arise only under very restrictive assumptions. The present paper demonstrates this in a transparent fashion and extends the analysis to the open economy. Here the equilibrium approach has the implausible implication that fiscal expansions, whether temporary or permanent, should “crowd in” investment.

Mesenchymal stem cells are multipotent cells resident in the bone marrow throughout adulthood which have the capacity to differentiate into cartilage, bone, fat, muscle, and tendon. A number of monoclonal antibodies raised against human MSCs have been shown to react with surface antigens on these cells in vitro. A protein of molecular mass 92 kDa was immunoprecipitated using the SH-2 monoclonal antibody. This was purified and identified by peptide sequencing analysis and mass spectrometry as endoglin (CD105), the TGF-beta receptor III present on endothelial cells, syncytiotrophoblasts, macrophages, and connective tissue stromal cells. Endoglin on MSCs potentially plays a role in TGF-beta signalling in the control of chondrogenic differentiation of MSCs and also in mediating interactions between MSCs and haematopoietic cells in the bone marrow microenvironment.

Bone marrow contains a rare population of mesenchymal stem cells (MSCs) capable of giving rise to multiple mesodermal tissues including bone, cartilage, tendon, muscle, and fat. The cell surface antigen recognized by monoclonal antibody SB-10 is expressed on human MSCs but is lost during their developmental progression into differentiated phenotypes. Here we report on the immunopurification of the SB-10 antigen and its identification as activated leukocyte-cell adhesion molecule (ALCAM). Mass spectrometry establishes that the molecular mass of ALCAM is 80,303 +/- 193 Da and that it possesses 17,763 +/- 237 Da of N-linked oligosaccharide substituents. Molecular cloning of a full-length cDNA from a MSC expression library demonstrates nucleotide sequence identity with ALCAM. We also identified ALCAM homologs in rat, rabbit, and canine MSCs, each of which is over 90% identical to human ALCAM in their peptide sequence. The addition of antibody SB-10 Fab fragments to human MSCs undergoing osteogenic differentiation in vitro accelerated the process, thereby implicating a role for ALCAM during bone morphogenesis and adding ALCAM to the group of cell adhesion molecules involved in osteogenesis. Together, these results provide evidence that ALCAM plays a critical role in the differentiation of mesenchymal tissues in multiple species across the phylogenetic tree.

In Irish manufacturing, the foreign sector accounts for about one half of employment and some 60% of gross output. The Irish experience therefore provides us with a textbook case study of the effects on an EU host economy of export-oriented FDI. We explore in this paper the structural changes induced by FDI and the effects of FDI on the determinants of growth in Ireland. We also consider some possible adverse effects that may be associated with such strong reliance on multinational investment.

Analysis of the carboxymethylated subunit of human cartilage oligomeric matrix protein (COMP) by matrix-assisted laser desorption time-of-flight mass spectrometry indicated a protonated molecular mass of 86949 ± 149 Da, compared with 83547.0 Da calculated from the sequence. Treatment withN-glycanase caused a reduction in mass of 3571 ± 219 Da, but there was no loss of mass after treatment withO-glycanase or neuraminidase. Peptides containing two putative sites of N-glycosylation were purified and characterized. Analysis of the masses of these afterN-glycanase treatment indicated that one was substituted at Asn-101 with an oligosaccharide of mass 1847.2 ± 6.6 Da, and the other was unsubstituted at Asn-124. The remaining site of attachment, at Asn-721, was, therefore, also substituted with an oligosaccharide of mass 1724 ± 226 Da. Analysis of the total monosaccharide content by chemical methods indicated that there were no additional oligosaccharide substituents. The MALDI-TOF mass spectra of COMP from bovine fetal and adult cartilage were compared, indicating a more heterogeneous pattern of substitution at Asn-101 in the fetal form. Since COMP is distributed throughout the pericellular and territorial environments in developing cartilage but occupies the interterritorial zone in mature cartilage, these changes in glycosylation may allow for different intermolecular interactions.

This book provides authoritative academic and professional insights into the effects of FDI on home and host countries. It highlights global trends and patterns, and explores related policy challenges all with a special focus on the countries in Central, Eastern and South-Eastern Europe. The book cuts through the existing data fog by offering a wide range of up-to-date academic findings and institutional expertise. Those findings are rounded off with lessons to be learned from historical developments (Ireland’s success story), an evaluation of current trends (role of China) and an investment promotion agency policy for attracting sustainable investment (CzechInvest).

This unique, extensive Handbook illustrates that multinational enterprises can contribute substantially to the competitive advantage of small countries. It advances the notion that small nations increasingly need to rely on both home-grown and foreign multinational enterprises to achieve domestic economic success in industries characterized by international competition.

Allogeneic mesenchymal stem cells (allo-MSCs) have potent regenerative and immunosuppressive potential and are being investigated as a therapy for osteoarthritis; however, little is known about the immunological changes that occur in allo-MSCs after ex vivo induced or in vivo differentiation. Three-dimensional chondrogenic differentiation was induced in an alginate matrix, which served to immobilize and potentially protect MSCs at the site of implantation. We show that allogeneic differentiated MSCs lost the ability to inhibit T-cell proliferation in vitro, in association with reduced nitric oxide and prostaglandin E2 secretion. Differentiation altered immunogenicity as evidenced by induced proliferation of allogeneic T cells and increased susceptibility to cytotoxic lysis by allo-specific T cells. Undifferentiated or differentiated allo-MSCs were implanted subcutaneously, with and without alginate encapsulation. Increased CD3(+) and CD68(+) infiltration was evident in differentiated and splenocyte encapsulated implants only. Without encapsulation, increased local memory T-cell responses were detectable in recipients of undifferentiated and differentiated MSCs; however, only differentiated MSCs induced systemic memory T-cell responses. In recipients of encapsulated allogeneic cells, only differentiated allo-MSCs induced memory T-cell responses locally and systemically. Systemic alloimmune responses to differentiated MSCs indicate immunogenicity regardless of alginate encapsulation and may require immunosuppressive therapy for -therapeutic use.

Mesenchymal Stem Cells are known to engraft and integrate into the architecture of colorectal tumours, with little known regarding their fate following engraftment. This study aimed to investigate mediators of Mesenchymal Stem Cell (MSC) and colon cancer cell (CCC) interactions. Mesenchymal Stem Cells and colon cancer cells (HT29 and HCT-116) were cultured individually or in co-culture on 3-dimensional scaffolds. Conditioned media containing all secreted factors was harvested at day 1, 3 and 7. Chemokine secretion and expression were analyzed by Chemi-array, ELISA (Macrophage migration inhibitory factor (MIF), plasminogen activator inhibitor type 1 (PAI-1)) and RQ-PCR. Colon cancer cell migration and proliferation in response to recombinant PAI-1, MSCs and MSCs + antibody to PAI-1 was analyzed using Transwell inserts and an MTS proliferation assay respectively. Chemi-array revealed secretion of a wide range of factors by each cell population, including PAI-1and MIF. ELISA analysis revealed Mesenchymal Stem Cells to secrete the highest levels of PAI-1 (MSC mean 10.6 ng/mL, CCC mean 1.01 ng/mL), while colon cancer cells were the principal source of MIF. MSC-secreted PAI-1 stimulated significant migration of both CCC lines, with an antibody to the chemokine shown to block this effect (67–88% blocking,). A cell-line dependant effect on CCC proliferation was shown for Mesenchymal Stem Cell-secreted PAI-1 with HCT-116 cells showing decreased proliferation at all concentrations, and HT29 cells showing increased proliferation in the presence of higher PAI-1 levels. This is the first study to identify PAI-1 as an important mediator of Mesenchymal Stem Cell/colon cancer cell interactions and highlights the significant functional impact of Mesenchymal Stem Cell-secreted PAI-1 on colon cancer cells. Deposited by bulk import