Reconstructing the Social Fabric amid On-going Violence: Attitudes toward Reconciliation and Structural Transformation in Colombia

Given the increase of reconciliation processes initiated amid on-going violence, this study focuses on community reconciliation and its relation to structural transformation, or social reconstruction through reforming unjust institutions and practices that facilitate protracted violent conflict. Drawing lessons from the Caribbean coast of Colombia, mixed method analyses include eight in-depth interviews and 184 surveys. Four key dimensions of reconciliation – truth, justice, mercy, peace – are examined. In the interviews, participants prioritize reconstructing the truth and bringing perpetrators to justice as essential aspects of reconciliation. Notions of mercy and forgiveness are less apparent. For the participants, sustainable peace is dependent on structural transformation to improve livelihoods. These data, however, do not indicate how this understanding of reconciliation may relate to individual participation in reconciliation processes. Complementing the qualitative data, quantitative analyses identify some broad patterns that relate to participation in reconciliation events. Compared to those who did not participate, individuals who engaged in reconciliation initiatives report higher levels of personal experience with violence, live alongside demobilized paramilitaries, are more engaged in civic life, and express greater preference for structural transformation. The paper concludes with policy implications that integrate reconciliation and structural transformation to deepen efforts to rebuild the social fabric amid violence.

Stoichiometric Molecularly Imprinted Polymers for the Recognition of Anti-Cancer Pro-drug Tegafur

Molecularly Imprinted Polymers (MIPs) targeting tegafur, an anti-cancer 5-fluorouracil pro-drug, have been prepared by stoichiometric imprinting using 2,6-bis(acrylamido)pyridine (BAAPy) as the functional monomer. Solution association between tegafur and BAAPy was studied by 1H NMR titration, which confirmed the formation of 1:1 complexes with an affinity constant of 574±15 M-1 ¬in CDCl3. Evaluation of the synthesised materials by HPLC and equilibrium rebinding experiments revealed high selectivity of the imprinted polymer for the pro-drug versus 5-fluorouracil and other competing analytes, with maximum imprinting factors of 25.3 and a binding capacity of 45.1 μmol g-1. The synthesised imprinted polymer was employed in solid-phase extraction of the pro-drug using an optimised protocol that included a simple wash with the porogen used in the preparation of the material. Tegafur recoveries of up to 96% were achieved from aqueous samples and 92% from urine samples spiked with the template and three competing analytes. The results demonstrate the potential of the prepared polymers in the pre-concentration of tegafur from biological samples, which could be an invaluable tool in the monitoring of patient compliance and drug uptake and excretion.

Pro-neural transcription factors as cancer markers

BACKGROUND: The aberrant transcription in cancer of genes normally associated with embryonic tissue differentiation at various organ sites may be a hallmark of tumour progression. For example, neuroendocrine differentiation is found more commonly in cancers destined to progress, including prostate and lung. We sought to identify proteins which are involved in neuroendocrine differentiation and differentially expressed in aggressive/metastatic tumours.

RESULTS: Expression arrays were used to identify up-regulated transcripts in a neuroendocrine (NE) transgenic mouse model of prostate cancer. Amongst these were several genes normally expressed in neural tissues, including the pro-neural transcription factors Ascl1 and Hes6. Using quantitative RT-PCR and immuno-histochemistry we showed that these same genes were highly expressed in castrate resistant, metastatic LNCaP cell-lines. Finally we performed a meta-analysis on expression array datasets from human clinical material. The expression of these pro-neural transcripts effectively segregates metastatic from localised prostate cancer and benign tissue as well as sub-clustering a variety of other human cancers.

CONCLUSION: By focussing on transcription factors known to drive normal tissue development and comparing expression signatures for normal and malignant mouse tissues we have identified two transcription factors, Ascl1 and Hes6, which appear effective markers for an aggressive phenotype in all prostate models and tissues examined. We suggest that the aberrant initiation of differentiation programs may confer a selective advantage on cells in all contexts and this approach to identify biomarkers therefore has the potential to uncover proteins equally applicable to pre-clinical and clinical cancer biology.

Targeting translocator protein (18 kDa) (TSPO) dampens pro-inflammatory microglia reactivity in the retina and protects from degeneration

BACKGROUND: Reactive microglia are commonly seen in retinal degenerative diseases, and neurotoxic microglia responses can contribute to photoreceptor cell death. We and others have previously shown that translocator protein (18 kDa) (TSPO) is highly induced in retinal degenerations and that the selective TSPO ligand XBD173 (AC-5216, emapunil) exerts strong anti-inflammatory effects on microglia in vitro and ex vivo. Here, we investigated whether targeting TSPO with XBD173 has immuno-modulatory and neuroprotective functions in two mouse models of acute retinal degeneration using bright white light exposure.

METHODS: BALB/cJ and Cx3cr1 (GFP/+) mice received intraperitoneal injections of 10 mg/kg XBD173 or vehicle for five consecutive days, starting 1 day prior to exposure to either 15,000 lux white light for 1 h or 50,000 lux focal light for 10 min, respectively. The effects of XBD173 treatment on microglia and Müller cell reactivity were analyzed by immuno-stainings of retinal sections and flat mounts, fluorescence-activated cell sorting (FACS) analysis, and mRNA expression of microglia markers using quantitative real-time PCR (qRT-PCR). Optical coherence tomography (OCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stainings, and morphometric analyses were used to quantify the extent of retinal degeneration and photoreceptor apoptosis.

RESULTS: Four days after the mice were challenged with bright white light, a large number of amoeboid-shaped alerted microglia appeared in the degenerating outer retina, which was nearly completely prevented by treatment with XBD173. This treatment also down-regulated the expression of TSPO protein in microglia but did not change the TSPO levels in the retinal pigment epithelium (RPE). RT-PCR analysis showed that the microglia/macrophage markers Cd68 and activated microglia/macrophage whey acidic protein (Amwap) as well as the pro-inflammatory genes Ccl2 and Il6 were reduced after XBD173 treatment. Light-induced degeneration of the outer retina was nearly fully blocked by XBD173 treatment. We further confirmed these findings in an independent mouse model of focal light damage. Retinas of animals receiving XBD173 therapy displayed significantly more ramified non-reactive microglia and more viable arrestin-positive cone photoreceptors than vehicle controls.

CONCLUSIONS: Targeting TSPO with XBD173 effectively counter-regulates microgliosis and ameliorates light-induced retinal damage, highlighting a new pharmacological concept for the treatment of retinal degenerations.

EFFECTS OF ENVIRONMENTAL ANTIOXIDANTS ON PRO-ANGIOGENIC ROS SIGNALLING IN ENDOTHELIAL COLONY FORMING CELLS IN VITRO

Introduction. Endothelial colony-forming cells (ECFCs) hold great cytotherapeutic potential for ischaemic disease. Whilst increasing evidence supports a key role for reactive oxygen species (ROS), specifically those derived from Nox NADPH oxidases, in the underlying angiogenic processes of these and other endothelial cells, such studies investigating the role of redox signalling may be hampered by the standard inclusion of antioxidant agents in endothelial cell media, such as phenol red. Aims. To study the effects of antioxidants present in culture media on pro-angiogenic function of ECFCs in vitro. Methods. Human ECFCs isolated from umbilical cord blood were maintained in media with and without antioxidant components (EGM2 and phenol red-free DMEM, respectively) prior to treatment with pro-oxidant PMA and assessment of their in vitro migratory capacity using a scratch-wound assay to measure pro-angiogenic activity. Results. Our previous work in our group indicated that PMA (500nM) increased ECFC migration in a both a superoxide and NADPH oxidase-dependent manner (control 18.6±2.8, PMA 32.7±6.6% wound closure; n=6, P<0.05), as indicated by attenuation with PEG-SOD and VAS2870. However, inconsistencies in the data generated under varying experimental conditions led us to hypothesise that antioxidant agents in the standard ECFC media may be influencing these effects. Indeed, a direct comparison of cell migration between ECFCs incubated in EGM2 DMEM demonstrated a clear trend towards higher migration in the latter (EGM2 9.0±4.5, DMEM 22.7±6.4%; n=3, P=NS). Similar to our previous EGM2 studies, cell migration was potentiated by PMA (control 11.6±1.6, PMA 25.1±2.8%; n=3, P<0.05), but at a lower dose (100nM), which is consistent with a reduction in media antioxidants. Notably, this response was attenuated by VAS2870 (PMA 37.6±7.3, PMA+VAS2870 10.3±2.9%; n=6, P<0.05), underlining a likely role for Nox NADPH oxidases. Conclusion. Taken together, these data indicate that ECFC migration is sensitive to different endothelial cell growth media, which appears to be dependent upon their antioxidant content. Although further experiments, such as quantification of cellular superoxide generation by dihydroethidium fluorescence may be required to confirm a specific role for antioxidants, such blunting of ROS signalling in vitro is clearly an important consideration which may significantly impact upon data interpretation.

Grupos étnicos de Colombia: Etnografía y bibliografía

El presente trabajo quiere presentar un panorama de los grupos étnicos indígenas que hoy pueblan el territorio colombiano. La "visión etnológica sobre los grupos étnicos indígenas actuales de Colombia con su bibliografía" tiene como objeto presentar la riqueza étnica de las minorías indígenas que, junto con los negros y blancos, conforman el pueblo colombiano. Como lo indica el título, esta no es una investigación profunda sobre cada grupo, pero es una recopilación de datos, informes y libros ya existentes para dar una visión de cada grupo étnico mencionado, aunque sobre algunos los datos son escasos, por varias razones que especialmente debido a la poca literatura eústente en la etnología actual. Después del índice, la introducción y agradecimientos, se encuentra la bibliografia general, a la cual sigue la presentación de los deparamentos, intendencias y comisarías donde existen los resguardos y las reservas indígenas, complementados al final del trabajo con su respectivo mapa; en cada resguardo o reserva aparece entre paréntesis el número bajo el cual se puede buscar en el mapa. A continuación se éncuentta la clasificación de los grupos étnicos por familias lingüísticas y la descripción de cada uno, ordenados alfabéticamente, divididos en subtítulos como nominación, o bajo cuales nombres se conoce el grupo, localización, resguardos y/o reservas indígenas, lengua y/o familia linguística a Ia cual pertenece, vivienda, economía, vestidos y adornos, organización socio-política, creencias y rituales, aculturación. Aunque los subtítulos no se compaften siempre, debido a la escasez de trabajos sobre algunos grupos y/o a su falta de disponibilidad, espero que aún de este modo el presente trabajo será de utilidad y por ello despuás de cada gupo se menciona la bibliografía de los trabajos existentes sobre el mismo, para quienes quieran profundizar sus conocimientos sobre el tema.

Traduções portuguesas do Pro Archia de Cícero

Este estudo pretende, num primeiro momento, identificar as traduções portuguesas do discurso de Cícero Pro Archia , os seus autores e o contexto histórico e cultural em que foram produzidas. As traduções inéditas encontram- -se aqui editadas e as edições impressas com mais de uma edição têm uma edição crítica. Há ainda lugar a uma reflexão sobre as possíveis edições latinas do Pro Archia consultadas pelos tradutores. O segundo momento é dedicado à análise comparativa destas traduções, que assenta quer em aspectos linguísticos e lexicais específicos quer nos processos de tradução de cada texto, relacionando-os com o contexto de produção de cada uma.

Pro-internationalisation policies and outward foreign direct investment

This thesis addresses the impacts of public policies on outward foreign direct investment, seeking to contribute to a better understanding of the interplay between pro-internationalisation policies and firm behaviour. Home country measures associated with these policies are explored in terms of use and awareness, as determinants of foreign direct investment, as drivers of policy objectives, in terms of perceived importance and impact in different scenarios of internationalisation. Using a comprehensive database of 441 Portuguese firms, being those that had participated at least in one of the 11 types of public support between 1994 and 2009. The empirical papers presented here reveal a moderating effect of firm capabilities and internationalisation conditions on policy objectives. In fact, firms’ resources and capabilities frame the awareness and use of home country support measures, the existence of public policy determinants of foreign direct investment, the decision to carry out more aggressive modes of entry and the choice of more demanding environments, the impact of policy objectives, and the perceived importance of incentives. In practical terms, the findings of this thesis points that firms’ resources and capabilities are negatively associated with the use of public support, contrasting with awareness, which is found to increase with firms’ resources and capabilities. This insight sheds light on a potential problem of incentives allocation. Our results support the established theorizing about the co-evolution of government and firms' policies, home country measures being found as determinants of foreign direct investment. It is also shown that prointernationalization policies reinforce the firms’ resources and capabilities, which seems to have a positive impact on international growth. An evaluation of public policy, from the foreign direct investor's lens, supports the argument that firms involved in more demanding projects tend to attribute more importance to public supports. Behind the specific and concrete contributions identified in each of the empirical papers, as a whole this thesis makes methodological contributions by introducing the evaluation of impacts of public policies to the field of international business through the firm perspective; these contributions are achieved by taking the pro-internationalisation policies of a small open economy to better understand the impacts of public policies, and by shedding light on co-evolution between resource and institutional-based views.