634 research outputs found

    Think Tanks and Poverty in Latin America: The role of thinkers in the marketplace of social policies in Argentina, Chile and Mexico

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    The high levels of poverty and inequity that affect a large portion of Latin American population is among the main issues that the region faces. According to CEPAL (2007), 36,5% of the population of the region (194 million) is below the poverty line, while 13,4% (71 million) is below the extreme poverty line. Even though this issue has been present in the public policy agenda for a long time, it is in the last decades that the repeated socio economic crisis that affected the region have significantly increased the concern for this issue. Without doubt, finding solutions for such a wide and complex matter -as is the lack of resources and opportunities of a great portion of the population- requires a significant effort, not only from governments and public bureaucracies, but also from a wider range of actors that can participate and offer alternatives to face and gradually solve the problem. In this context, social policies are of great relevance for helping reduce poverty, specially considering the weakening of formal labour as the main source of social integration. In this context, the role that different actors play, including government, academic institutions, think tanks or other civil society organizations constitutes an aspect that should be analyzed in greater depth. However, even though the significant relevance of social policies, and the increasing participation of different civil society institutions that produce knowledge and try to influence policy decisions, the ways in which these actors participate in the social policy process is a subject of study which has been insufficiently explored. The premise is that analyzing and better understanding the role and interests of all actors involved in the social public policy process leads to a better understanding the results obtained with such policies. Taking this into account, the objective of this research is to make a first approach in the analysis of the means and levels of involvement of think tanks and individual Experts in the area –specialists, academics, or professional researchers- in the different stages of social policy making in Latin America.Think Tanks; América Latina; pobreza; Gerardo Una; Carina Lupica; Luciano Strazza; Progresa; Plan Jefes y Jefas; Chile Solidario

    Improvement of antitumor therapies based on vaccines and immune-checkpoint inhibitors by counteracting tumor-immunostimulationw

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    Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors), counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth.Fil: Chiarella, Paula. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Vermeulen, Mónica. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Montagna, Daniela R.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Vallecorsa, Pablo. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Strazza, Ariel Ramiro. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Bustuoabad, Oscar D.. Retired; ArgentinaFil: Ruggiero, Raúl A.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Prehn, Richmond T.. University Of Washington, Seattle

    "Identification of human monoclonal antibodies from single cells: two different approaches in the context of infectious diseases"

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    In the age of personalised medicine, creating and producing molecules with strong affinity and specificity, like monoclonal Antibodies (mAbs), presents a great research opportunity. Various techniques exist for large-scale mAb production, making them one of the most powerful tools both for research and therapy. However, the identification of monoclonal antibodies with the desired characteristics of affinity, functional activity and developability still remains a challenging task for scientists. In this context, single B cell isolation methods have become a crucial research technique to interrogate the immune repertoire in humans. This thesis aimed to investigate the feasibility, efficiency and efficacy of two distinct methods to generate monoclonal antibodies from single B cells in the context of infectious diseases. Study A was carried out at Toscana Life Sciences (TLS) in the HARD Lab group, with the support of the University of Siena while, Study B was carried out at the Department of Biochemistry of Oxford University, in the Draper Lab group. The objective of study A was to establish a rapid and efficient workflow for the generation of human recombinant monoclonal antibodies using an innovative Fluorescence Activated Cell Sorting (FACS)-free technology based on Ferrofluid particles. Starting from single Antibody Secreting Cells (ASCs), enriched for the marker CD138 by magnetic cell sorting, cells were selected for their antigen-specificity by Enzyme-Linked ImmunoSorbent Assay (ELISA) of their cell culture supernatants. These cells were then used to generate recombinant mAbs by direct transfection of PCR fragments called “minigenes”, containing variable regions of the mAbs, which were validated by ELISA for specificity to the antigen of interest. In the context of the pandemic situation, the SARS-CoV-2 infection was considered a good opportunity to test the feasibility of generating mAbs using this platform, starting from the peripheral blood of convalescent COVID-19 donors who had recovered from the disease. In this proof-of-concept study, we aimed to develop a method and demonstrate the feasibility of this in less than 10 days, while pooling a panel of SARS-CoV-2 Spike-specific mAbs for further characterisation of functional activity by neutralisation assays. The aim of study B was to isolate antimalarial human mAbs against the Plasmodium falciparum Reticulocyte-binding protein Homolog 5 (RH5) antigen. RH5 is currently a leading blood-stage malaria vaccine target and clinical trials of vaccines containing this antigen are ongoing. It plays an essential role in parasite invasion of erythrocytes as part of the PCRCR invasion complex and, through its interaction with basigin, it is a major target of growth inhibitory antibodies. Immunity directed against the blood-stage is unique because it would allow for the development of naturally-acquired immunity and reduce morbidity and mortality. However, antibody-mediated immunity against the blood stage requires high levels of antibodies, which has been difficult to achieve thus far. Starting with PBMCs samples from RH5-vaccinated volunteers, antigen-specific memory B cells were single-cell sorted by FACS using fluorescently-labelled RH5 antigen probes. While a large number of RH5-specific antibodies have been generated previously by the Draper group, the focus of this part of the thesis was to isolate human mAbs that bind to uncharacterised regions on RH5, potentially identifying new sites of vulnerability on RH5 or “inert” sites that could be excluded from RH5 in next-generation vaccine designs to improve the response. Here we have developed a repertoire of mAbs from the peripheral blood of UK adults vaccinated with PfRH5 (VAC063 trial), a vaccine reported to be safe and immunogenic in phase I/IIa (PfRH5 in adjuvant VAC063 clinical trial, NCT02927145). We generated two new panels of mAbs: one against the full-length RH5 protein (RH5.1) and one against the N-terminus portion of the protein (RH5-NT). The mAbs in the second panel will also be used to investigate the biological role of the N-terminus, which is still unclear. Both panels of mAbs were characterised by ELISA and an in vitro parasite Growth Inhibition Assay (GIA). Although both projects have common aspects, the first study is more focused on establishing a methodology to develop mAbs in a rapid and reliable way, while the second study uses an established antibody discovery pipeline and aims to develop and characterise two panels of mAbs and provide more information in the context of vaccine design

    "Hola, mi amor. Yo soy el lobo"

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    En este artículo se analiza la presencia del erotismo como tema central en la obra poética de Luis Alberto de Cuenca. Primeramente, se realiza una revisión crítica que comenta la presencia del elemento amoroso y erótico en la poesía cuenquista; y finalmente, se propone el estudio de un corpus poético para tratar de manera exhaustiva el argumento. This paper focuses on the presence of erotism as main theme in the poetic work of Luis Alberto de Cuenca. First of all, it presents a critical review about the presence of love and erotism in his poetry. Last but not least, it suggests a study of his poetic work with the aim of discussing the argument exhaustively.In questo articolo si analizza la presenza dell'erotismo come tema centrale nell'opera poetica di Luis Alberto de Cuenca. In primo luogo, si realizza una revisione critica che commetna la presenza dell'elemento amoroso ed erotico nella poesia dell'autore. Infine si propone uno studio del corpus poetico al fine di trattare l'argomento in maniera esaustiva.  This paper focuses on the presence of erotism as main theme in the poetic work of Luis Alberto de Cuenca. First of all, it presents a critical review about the presence of love and erotism in his poetry. Last but not least, it suggests a study of his poetic work with the aim of discussing the argument exhaustively

    Analisi geochimiche su materia organica (delta 13 C org) e indagini su framboidi di pirite come proxi di anossia della sezione Pignola 2, bacino di Lagonegro, Potenza

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    In the Carnian (Upper Triassic) a period of increasing rainfall, named Carnian Pluvial Episode (CPE), is evidenced by lithological changes in various successions in the world. The environmental change seems to be closely associated with a global carbon cycle perturbation that was identified in stratigraphic successions of the Southern Alps of Italy, Northern Calcareous Alps of Austria, Hungary, South China and UK. This thesis presents organic carbon isotope data and ocean redox condition based on framboidal pyrite from Pignola 2, a Carnian deep-water stratigraphic section. Organic carbon isotope data show two negative δ13Corg shift within the CPE. The first, of about 3.5‰, within the Julian 2, and the second, of about 2‰, at the Julian/Tuvalian boundary. The investigation of framboidal pyrite suggests anoxic condition at the base of the CPE. These observations verify that sedimentological changes related to the CPE coincide with the carbon cycle perturbation and therefore occurred synchronously also in the Pignola 2 section. The injection of light CO2 into the Carnian atmosphere-ocean system may have been directly responsible for both the recorded two negative δ13Corg shift and the increase in rainfall. The consequent increased continental weathering led to the transfer of large amounts of siliciclastics sediments into the basins, while the increased run-off and nutrient flux triggered the development of anoxiaope

    PLCε1 suppresses tumor growth by regulating murine T cell mobilization

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/1/cei13409.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/2/cei13409_am.pd
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