Active management in mutual funds with concentrated benchmarks: A major dilemma to fulfill the EU directive on portfolio concentration limits.

his doctoral thesis is focused on the increasing importance of mutual funds as saving vehicles for the finances of individuals in the economies of developed countries over the last half of the twentieth century. Among them, the equity funds that take the form of open-end funds like mutual funds are becoming one of the most relevant instruments. Mutual funds collect money from investors and invest it in stocks, bonds, other funds, and so on, and their performance depends on the mix of the allocated securities. Its main objectives were to contribute to the topic of the Active Share (AS) as applied to mutual funds in Eurozone countries. This investigation was mainly motivated by the need to analyse how both the level of concentration of the benchmarks and the level of concentration of the mutual fund industries in the Eurozone affect active management. Due to the scarce number of studies focused on this topic in Europe our results have relevant implications to investors, market supervisors, and policymakers. In Chapter 1, we analysed how article 52 in Directive 2009/65/EC (UCITS IV) on risk of portfolio diversification could distort the accuracy of AS due to the higher level of concentration in Eurozone domestic benchmarks. In this chapter, we were able to identify truly active management in Eurozone mutual funds. Thus, we developed an algorithm to capture the spurious AS (sAS), which is defined as the minimum AS, that is not a consequence of active decisions made by equity fund managers. The results provide evidence that the Directive negatively influences the accuracy of the AS shown for managers who work with very concentrated domestic Eurozone benchmarks such as the PSI 20 (Portugal), ATX 20 (Austria), and IBEX 35 (Spain). In contrast, the evidence from the sAS for the least concentrated domestic Eurozone benchmarks shows that AS reported by managers who work in France, Germany, and Finland are much more accurate. Hence, these results prove that direct AS comparisons in the Eurozone are not feasible and lead us to obtain three AS thresholds per domestic equity benchmark, which are the minimum values of AS needed to confirm that domestic equity funds are significantly active at 90%, 95%, and 99% confidence levels.We also analysed the level of active management in the domestic equity funds registered in each Eurozone country. Our findings also show that the high concentration level and the heterogeneity present in the domestic equity funds in the Eurozone prevent the direct comparability of the AS. Therefore, we had to consider the level of AS over the spurious level and the characteristics of each market that produces significant and different styles of active management. For that, we formulated an actual active share (aAS) that considered the level of concentration in the domestic equity funds of the Eurozone markets and the limits of the portfolio concentration on European regulation. We define aAS as the difference between the monthly AS obtained for each domestic equity fund minus its monthly AS threshold obtained previously at 90%, 95%, and 99% confidence levels. Focusing on the most relevant mutual fund industries in the Eurozone countries, we find that France is the most active domestic equity fund market. Spanish and Italian markets also show high levels of actual active management despite the large concentration in their domestic benchmarks. Conversely, domestic equity funds registered in Germany show lower levels of active management. Our research results support the hypothesis that aAS corrects the potential bias in the original AS caused by both the domestic benchmark concentration and the EU portfolio diversification rules.In summary, our study is the first to evaluate the consequences of both the assorted characteristics of domestic Eurozone benchmarks and the European regulation that prevents portfolio concentration (UCITS IV) in the appropriate estimation of AS. Furthermore, our study identifies truly active management in domestic equity funds in the Eurozone markets. This chapter has important implications for policymakers and practitioners of the domestic equity funds in the Eurozone. In the strongly regulated European markets, our unbiased approach allows both investors and market supervisors to identify the accurate levels of active management of each industry after considering both the regulation of portfolio diversification and the concentrated domestic equity benchmarks. Market supervisors will have a better picture of the active management map to develop appropriate regulations for the mutual fund industry. In addition, our approach should help practitioners and investors to effectively find out the level of active management of domestic equity funds and therefore provide information for fund management companies to replace actual performing managers. Further, our results should help to reduce the opacity in the management fees that funds charge by providing accurate measures of active management. In Chapter 2, we analysed how some market and fund characteristics play a crucial role in explaining the portfolio concentration default on Directive 2009/65/EC (UCITS IV). This chapter should help market supervisors to improve the monitoring process of defaults by domestic equity funds in the Eurozone mutual fund industries. On the one hand, the origin of UCITS directives was considered the beginning towards market protection and increased transparency in the Eurozone. On the other hand, the structure of mutual funds allows retail investors to access sophisticated active strategies that comply with liquidity and transparency restrictions protected by regulatory oversight. Their rules are based on a certain degree of portfolio diversification with the goal of reducing their vulnerability to portfolio risks. This chapter is the first to analyse how concentrated strategies could lead to non-compliance with article 52 in UCITS IV. First, we analysed several market characteristics that may influence the probability of a fund manager failing to meet the portfolio concentration limits. Using a logic panel data model (fixed effects), we estimated the probability of incurring defaults. Our findings provide evidence that should lead market supervisors to pay attention to concentrated fund industries with concentrated domestic benchmarks to prevent defaults on Eurozone concentration limit. The level of concentration of the domestic equity benchmarks would make the defaults almost twice as likely to occur. The level of concentration of the domestic fund industry also has positive and significant effects on the likelihood of incurring defaults. That is, defaults are approximately 12% to 17% more likely to occur when the level of concentration in the domestic fund industry increases. This evidence is consistent with the findings in the literature that link competition with active management strategies such as concentrated portfolios (see Dyck et al., 2013). Second, in the same line of Chapter 1, we analysed several funds characteristics that may influence the probability of a fund manager failing to meet the portfolio concentration limits. In Eurozone markets, market supervisors should especially monitor the most experienced funds that are solo-managed to prevent portfolio weights over the 10% limit. This finding is in accordance with Goldman et al., (2016) who shows that individual managers have much more concentrated portfolios than management teams. The fund’s age has a positive and significant influence on the likelihood of defaults. That is, the probability of incurring defaults is approximately 18% to 26% higher among older funds. Thus, this evidence is in accordance with the literature that links older funds with higher levels of idiosyncratic risk as a consequence of having more concentrated portfolios (see Amihud and Goyenko, 2013). Further, we analysed the characteristics of those stocks that were especially subject to more concentrated strategies and, therefore, more vulnerable to mutual funds’ investment policies. For that, we applied a multinomial logic panel data model (fixed effects) and found that the weight of the stocks in their benchmarks had a positive and significant effect on default on the EU portfolio concentration limit. The results show how the probability of a stock being subject to default is approximately 8% to 25% higher when the stock weight in the domestic benchmark increases. Thus, market supervisors should monitor stocks with large weights in domestic equity benchmarks.In addition, we also find how the stocks of domestic benchmarks that have been held longer are likely to be subject to concentration defaults. That is, defaults are approximately 13% to 24% more likely to occur when choosing stocks that belong to the benchmarks during the last 24 months. Thus, this result is consistent with the literature that argues the local advantage of reducing information asymmetry problems.Thus, we find how stocks that present low volatility have a greater likelihood of being subject to non-compliance with EU portfolio concentration limits. In terms of percentages, the probability approximately lowers between 19% to 27% when stock volatility increases. This finding is in accordance with the commitment to controlled risk strategies (see Huang et al., 2011). Therefore, market supervisors should pay more attention to these stock characteristics to monitor stocks that are more frequently overweighted above EU concentration limits. In summary, this chapter is the first to both analyse and identify the determinants of domestic equity funds’ failure to comply with the portfolio concentration limits of EU Directive 2009/65/EC. Furthermore, our study also determines the characteristics of the stocks subject to these non-compliant portfolios in domestic equity funds in the Eurozone. This chapter has important implications for market supervisors and policymakers in the mutual fund industries of the Eurozone. Our approach allows market supervisors with limited resources to identify and control non-compliant domestic equity funds by monitoring only some fund-specific characteristics. The improvement of this monitoring process should contribute to the financial stability of the EU asset management industry in terms of investor protection and market transparency. That is, mutual fund unitholders should be completely certain that their money is allocated to portfolios fulfilling the concentration limits required by the EU. Our findings also show a tool to assist EU market supervisors in identifying some explanatory mechanisms for stock weights that are over the EU concentration limits. Thus, our results may help supervisors identify what kind of domestic equity funds are more inclined to default and what kind of stocks are likely overweighted by these funds. Market supervisors could especially monitor these stocks to verify that domestic equity funds are meeting the concentration limits. Market supervisors should focus their limited resources on these types of stocks held by domestic equity funds to prevent defaults in portfolio concentration. Finally, our approach could also help retail investors control their risk profiles in terms of exceeding portfolio concentration limits. This application is in line with the reinforcement of investor protection of portfolio concentration. Investors could be sure that domestic equity funds fully follow the diversification requirements and market transparency provided by the UCITS directives.Chapter 3 presents a new perspective in the analysis of active management. We introduced dynamism by proposing a new version of AS that considers how the managers deviate their portfolios in two consecutive periods. We define dynamic Active Share (dAS) as a measure to capture over time the actual level of activity by comparing the differences against the benchmark in two consecutive periods. Our measure captures not only the long and short static positions in each stock included in the benchmark but also the previous long (short) positions that have been overweighted (underweighted) in the next period. Thus, dAS allows us to divide between investment decisions driven to spread portfolio weights closer to the benchmark (i.e., decisions that lead to a lower differentiation to the benchmark) and the other which is further from the benchmark (i.e., decisions that lead to a higher differentiation). Focusing on the most relevant fund industries in the Eurozone, we analysed the predictive power of AS first. The best results were found in the Spanish industry and, with less robustness, in Germany, the Netherlands, Austria, and Belgium. France only shows this relationship in the long term when we consider the CAPM alpha; while Italy, Finland, Portugal, and Greece fail to offer significant results or even present negative relationships. These results indicate that the prediction ability of AS presents assorted results as this relation is less clear than that presented in the literature (Cremers and Petajisto, 2009) Second, we examined the influence on the prediction power for performance of AS by splitting stocks in the portfolios of our sample into benchmark and non-benchmark . The results allow us to identify how the high proportion of prediction ability for performance of AS is explained by the investment in non-benchmark stocks. Although the AS’s share of overweight or underweight benchmark stocks is really related to stock picking ability, investing in overweighted stocks may mean distortions in their performance evaluations that can lead to spurious contributions to portfolio performance.Third, we applied and analysed the predictive power of dAS. The results provided evidence that the performance of non-benchmark stocks in high AS funds did not extend to mutual funds with high dAS. Thus, this measure is less sensitive to the weight of the portfolio that is invested in non-benchmark securities that is very relevant in Eurozone countries where domestic benchmarks are highly concentrated. The main advantage of the dAS compared to the AS is that our measure provides more information and can be split according to different investment decisions. For that reason, we proposed splitting up the dAS to examine which trading decisions add value to the portfolio. Our most interesting results showed that German funds presents a robust relationship between selling investment decisions and subsequently better performance. This relationship was also found for Dutch, Austrian, and Portuguese funds but with actual limited significance. This finding is in accordance with the level of activity showed by these industries in Chapter 1.Further, we analysed the contributions to dAS that was generated by those trading decisions that might be considered as managers’ bets. These bets could be those decisions that increased holdings that were already overweighted (buy bets) or decrease those holdings that were already underweighted (sell bets). Our findings show as in Germany and in some cases in the Austrian and Portuguese industries that there is subsequent significantly better performance in buying decisions. Focusing on selling decisions, only Finnish funds show positive and strong beliefs and performance. The results for predicting performance show that those portfolios with a higher concentration of these bets offer subsequent abnormal returns as this prediction ability is even higher than the seminal AS in some of the markets in this study.Accordingly, the results shown in this chapter are an interesting addition to Cohen et al. (2010) who try to identify the trades in which the managers have more confidence. The empirical findings show that those mutual funds with trading decisions with a stronger belief from the manager (i.e., decisions that lead them to deviate even more from the benchmark) outperform the remaining funds, especially when buying decisions are considered. This evidence is consistent with Karoui and Patel (2020) who show that the benefit of AS lies in the selection decision rather than the weighting decision.In summary, Chapter 3 is the first to introduce a dynamic perspective on AS to capture managers’ activity and skill. This chapter is relevant for investors who should be interested in knowing whether their fund manager is active and whether their decisions on new investment opportunities add value to the portfolio (i.e., undervalued assets) or on the contrary, the fund manager is passive. The common argument is related to the fees because the management fees charged by these two types of funds should be different. In addition, the chapter is also relevant to regulators in order to adjust the management fees charged by management companies to the actual level of activity carried out by mutual funds. Several fields for further investigation have been identified in this dissertation. Regarding the EU Directive, an extensive test of the level of enforcement that the UCITS IV has implemented in each Eurozone country (including emerging markets) could be useful for making decisions about possible changes in the regulation. Furthermore, a complementary analysis of chapter VII in UCITS IV in terms of its appropriateness with the characteristics of each Eurozone country could allow a more complete assessment of the limits of portfolio concentration and the implementation of the protection to investors. In addition, this dissertation makes an important advance in the topic of active management to help further an analysis in other areas or regions with similar characteristics that could be relevant to the financial literature. <br /

Detection of Catecholamines Produced in Planktonic P. aeruginosa and S. aureus Treated with Adult Bovine Serum

Bacterial biofilms play a critical role in inducing and sustaining chronic wounds that are serious health threats. Bacterial biofilms can also be found on medical prosthetics and implants that sustain infections in patients and cause life threatening situations. Bacteria self-produce these sticky extracellular substances termed a biofilm which help them to adhere to each other forming a community of microorganisms. One of the major issues is that biofilms have antimicrobial characteristics and provide protection from the immune system; biofilms are found in over 80% of human bacterial infections. Formation of a bacterial biofilm occurs when an individual (planktonic) bacterial cell attaches to a surface such as collagen exposed in a wound. The planktonic bacterial cell then converts into a biofilm phenotype which allows it to grow and divide on the surface thereby forming layers of microcolonies. After maturation, which is characterized by the production of an extracellular matrix, cells detach from the biofilm and disperse to re-enter the planktonic mode and repeat the biofilm cycle. Under conditions of stress, namely injury or disease, the human body releases adrenaline-like hormones called catecholamines such as epinephrine (adrenaline) and norepinephrine (noradrenaline). Many studies have indicated a close relationship between the presence of catecholamine hormones in a human host and the growth, formation, and virulence of bacterial biofilms. Furthermore, studies from Dr. Isseroff’s dermatology lab at UC Davis confirm that the presence of these catecholamines at dermal wound sites impair the healing process by generating a cellular response through activation of beta-adrenergic receptors. However, few species of bacterial biofilms have been shown to produce catecholamines independently, and none have been shown to produce epinephrine. We examined two species of bacteria commonly found in chronic wounds, Pseudomonas aeruginosa(Gram negative) and Staphylococcus aureus (Gram positive), to determine whether they can produce catecholamines in eukaryotic cell growth conditions. We examined the supernatants of the media after the bacteria were cultured with 0% and 10% concentrations of Adult Bovine Serum (ABS) and then detected for the presence of catecholamines by High Pressure Liquid Chromatography Electrochemical Detection (HPLC-ED)

Transforming the news value chain in the social era: a technical perspective

Purpose: This paper develops a conceptual framework to unde rstand the influence that the social era is having on the value chain of the local news industry. We theoretically advance value chain theory by firstly, considering the influence of community type and age on consumption and secondly exploring the role that consumers can play in value adding activities. Our theoretical contribution lies in moving from a transactional approach towards consumer relationships in the value chain towards managing consumers as a source of relational value (e.g. co-creation and integrated perspectives). Design: The conceptual framework is theoretically positioned in relation to community and digital community practices in the social era. A series of research questions are presented, then these questions are explored drawing on empirical data from the PEW database. We then advance the framework further to consider news firm strategy towards its consumers. 15 in-depth executive interviews were conducted with local news organizations in the Manchester area of the UK. Findings: We illustrate that different types of communities (merging cohorts and locations) are influencing levels of technological and social connectivity within the value chain. We also find that the news industry is experimenting with reconfiguring its consumer relations from a purely transactional to a co-created and participatory value added activity in the social era. In terms of its policy impact our findings show that the whole strategic value chain ideology of the news industry needs to change radically; away from its largely transactional (and lack of trust) approach in the ability of consumers to create value in the supply chain (other than to buy a product) and, move towards much greater consumer involvement and participation in value chain processes (creation, production and distribution of news products and services). Originality/value: The change associated with social media and connec tivity is changing the way that different community types and consumer groups are now consuming and participating in news content creation. Unlike previous studies we show that there is variance and complexity in the levels of consumer participation by community type/age group. Using the PEW data we contribute to knowledge on the value creation strategy of news firms in the social era, by identifying how communicative, social and communicative logics influence value and co-creation activities in the local news supply chain. Through our interviews we advance value co-creation theory from its strategic and marketing origins to operational and supply chain implementation

A Comparison of Nutritional Habits, Physical Function and Psychological Constructs between Urban and Rural Costa Rican Older Adults

Purpose: To compare nutritional habits, physical function and psychological constructs between Costa Rican older adults from urban and rural zones.Methods: Male and female older adults aged ? 65 yr. from urban (n = 185) and rural (n = 109) Costa Rica were assessed on nutritional habits, physical function measures, and cognitive function by a face-to-face interview.Results: Rural older adults consumed more daily carbohydrates, protein, and energy at breakfast and lunch (p < 0.05 for all), and more carbohydrates (p ? 0.001), fat (p = 0.002), protein (p ? 0.001), and energy (p ? 0.001) at dinner than urban elderly. Aerobic power (p = 0.044) was higher in urban compared to rural elderly. A correlation was found between aerobic power and global fatigue (r = -0.20, p = 0.014) in urban elderly. Lifetime cognitive activity correlated to total energy (r = 0.37, p = 0.003), carbohydrate (r = 0.37, p = 0.002), and protein (r = 0.34, p = 0.005) consumption in rural elderly. Higher depression scores (p = 0.048), and lower lifetime cognitive activity were observed in urban compared to rural elderly (p = 0.004).Conclusion: The health profile is positive for either group depending on the variable analyzed, except for a higher aerobic power, which provides benefits to the entire cohort

Detecting polymeric nanoparticles with coherent anti-stokes Raman scattering microscopy in tissues exhibiting fixative-induced autofluorescence

© 2015 SPIE.Recent advances in pharmaceutical nanotechnology have enabled the development of nano-particulate medicines with enhanced drug performance. Although the fate of these nano-particles can be macroscopically tracked in the body (e.g. using radio-labeling techniques), there is little information about the sub-cellular scale mechanistic processes underlying the particle-tissue interactions, or how these interactions may correlate with pharmaceutical efficacy. To rationally engineer these nano-particles and thus optimize their performance, these mechanistic interactions must be fully understood. Coherent Anti-Stokes Raman scattering (CARS) microscopy provides a label-free means for visualizing biological samples, but can suffer from a strong non-resonant background in samples that are prepared using aldehyde-based fixatives. We demonstrate how formalin fixative affects the detection of polymeric nanoparticles within kidneys following oral administration using CARS microscopy, compared with samples that were snap-frozen. These findings have implications for clinical applications of CARS for probing nanoparticle distribution in tissue biopsies

Finite Element modeling of cell behavior under different biophysical stimuli: from passive to active behavior.

La mecanobiología celular se encarga del estudio del comportamiento de las células cuando son sometidas a cargas mecánicas y de los mecanismos de mecanotransducción que éstas tienen. Se sabe que las células son capaces de adaptarse al ambiente mecánico en el que se encuentran, pudiendo aumentar o disminuir su rigidez en función de la rigidez del sustrato que las rodea. Además, son capaces de cambiar de un modo de migración a otro, buscando el modo más eficiente de migrar dependiendo de las propiedades mecánicas de la matrizen la que se encuentren. Sin embargo, esta capacidad de adaptación también permite que algunas células tumorales cambien sus propiedades mecánicas para invadir otros órganos de manera más sencilla. Para ello, las células utilizan diferentes mecanismos de mecanotransducción que les permiten tomar este tipo de decisiones en función de lo que estén sintiendo mecánicamente.Descifrar y entender los mecanismos de mecanotransducción no es una tarea sencilla, sin embargo, los modelos computacionales ayudan a entender mejor qué está sintiendo la célula para tomar algunas de estas decisiones. Para ello, distintos autores han propuesta diferentes tipos de modelos computacionales, desde modelos basados en agente a modelos continuos, pasando por modelos híbridos, que han ido resolviendo parte de los mecanismos de mecanotransducción, aunque todavía quedan muchos de ellos sin resolver.En esta Tesis, se estudia cómo las células son capaces de sentir diferentes ambientes mecánicos de manera pasiva y activa. Para ello, se presentan tres modelos computacionales distintos que se resuelven utilizando el Método de los Elementos Finitos (MEF). Debido a la gran capacidad de las células para adaptarse al entorno y estar en constante remodelación, los modelos constitutivos de material para describir cada caso de estudio son diferentes en función del comportamiento predominante. Estos modelos muestran la respuesta mecánica que las células podrían estar percibiendo en diferentes condiciones. El primero es una célula fluyendo de forma pasiva por el interior de un citómetro donde el cambio en el perl de velocidad, provocado por el cambio de sección del canal, induce una deformación en la célula. El segundo es una célula migrando de forma lobopodial dentro de una matriz extracelular tridimensional, donde sus propiedades mecánicas dependen o no del nivel de deformación que soporte la matriz. Finalmente, el último de los modelos es un cultivo celular sobre una matriz donde se simula la infección por bacteria de algunas células del cultivo.Todos los modelos en conjunto pretenden dar a conocer los diferentes mecanismos de mecanotransducción que las células pueden utilizar para percibir su entorno y que podrían desencadenar importantes mecanismos biológicos.<br /

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin

Recent changes of water discharge and sediment load in the Yellow River basin, China

The Yellow River basin contributes approximately 6% of the sediment load from all river systems globally, and the annual runoff directly supports 12% of the Chinese population. As a result, describing and understanding recent variations of water discharge and sediment load under global change scenarios are of considerable importance. The present study considers the annual hydrologic series of the water discharge and sediment load of the Yellow River basin obtained from 15 gauging stations (10 mainstream, 5 tributaries). The Mann-Kendall test method was adopted to detect both gradual and abrupt change of hydrological series since the 1950s. With the exception of the area draining to the Upper Tangnaihai station, results indicate that both water discharge and sediment load have decreased significantly (p&lt;0.05). The declining trend is greater with distance downstream, and drainage area has a significant positive effect on the rate of decline. It is suggested that the abrupt change of the water discharge from the late 1980s to the early 1990s arose from human extraction, and that the abrupt change in sediment load was linked to disturbance from reservoir construction.Geography, PhysicalGeosciences, MultidisciplinarySCI(E)43ARTICLE4541-5613

Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research

A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ventral mesencephalon (hVM1). This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn). Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH+ neuron generation and expression of a neuronal mature marker (hNSE), we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experimentsThis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (formerly Science and Innovation; PLE2009-0101, SAF2010-17167), Comunidad Autónoma Madrid (S2011-BMD-2336), Instituto Salud Carlos III (RETICS TerCel, RD06/0010/0009) and European Union (Excell, NMP4-SL-2008-214706). This work was also supported by an institutional grant from Foundation Ramón Areces to the Center of Molecular Biology Severo Ocho