180 research outputs found

    Pseudogap and superconductivity in two-dimensional doped charge-transfer insulators

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    High-temperature superconductivity emerges in the CuO2_2 plane upon doping a Mott insulator. To ascertain the influence of Mott physics plus short-range correlations, we solve a three-band copper-oxide model in the charge-transfer regime using cellular dynamical mean-field theory with continuous-time quantum Monte Carlo as an impurity solver. We report the normal and superconducting phase diagram of this model as a function of doping, interaction strength and temperature. Upon hole doping of the charge-transfer insulator, the phase boundary between pseudogap and correlated metal consists of a first-order transition line at finite doping ending at a critical point, as in the one-band model. Beyond the endpoint, the phase boundary continues as a Widom crossover line, across which thermodynamic quantities peak. This phase boundary determines changes in the pairing mechanism and is an emergent phenomenon characteristic of doped Mott insulators, independent of many microscopic details. Broader implications are discussed.Comment: 6 pages, 4 figures and supplementary information; published versio

    Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells

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    BACKGROUND AIMS: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. METHODS: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. RESULTS: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. CONCLUSIONS: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection

    Antagonistic effects of nearest-neighbor repulsion on the superconducting pairing dynamics in the doped Mott insulator regime

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    The nearest-neighbor superexchange-mediated mechanism for d_{x^2-y^2}-wave superconductivity in the one-band Hubbard model faces the challenge that nearest-neighbor Coulomb repulsion can be larger than superexchange. To answer this question, we use cellular dynamical mean-field theory (CDMFT) with a continuous-time quantum Monte Carlo solver to determine the superconducting phase diagram as a function of temperature and doping for on-site repulsion U=9tU=9t and nearest-neighbor repulsion V=0,2t,4tV=0,2t,4t. In the underdoped regime, VV increases the CDMFT superconducting transition temperature TcdT_c^d even though it decreases the superconducting order parameter at low temperature for all dopings. However, VV decreases TcdT_c^d in the overdoped regime. We gain insight into these paradoxical results through a detailed study of the frequency dependence of the anomalous spectral function, extracted at finite temperature via the MaxEntAux method for analytic continuation. A systematic study of dynamical positive and negative contributions to pairing reveals that even though VV has a high-frequency depairing contribution, it also has a low frequency pairing contribution since it can reinforce superexchange through J=4t2/(UV)J=4t^2/(U-V). Retardation is thus crucial to understand pairing in doped Mott insulators, as suggested by previous zero-temperature studies. We also comment on the tendency to charge order for large VV and on the persistence of d-wave superconductivity over extended-ss or s+d-wave.Comment: Latex, 16 pages, 8 figure

    The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas

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    OBJECTIVES: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells. BACKGROUND: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering. However, the paradigm is now switching from the porcine to the human model. METHODS: To achieve our goal, human pancreata were decellularized with Triton-based solution and thoroughly characterized. Primary endpoints were complete cell and DNA clearance, preservation of ECM components, growth factors and stiffness, ability to induce angiogenesis, conservation of the framework of the innate vasculature, and immunogenicity. Secondary endpoint was hpaECMs’ ability to sustain growth and function of human islet and human primary pancreatic endothelial cells. RESULTS: Results show that hpaECMs can be successfully and consistently produced from human pancreata and maintain their innate molecular and spatial framework and stiffness, and vital growth factors. Importantly, hpaECMs inhibit human naïve CD4+ T-cell expansion in response to polyclonal stimuli by inducing their apoptosis and promoting their conversion into regulatory T cells. hpaECMs are cytocompatible and supportive of representative pancreatic cell types. DISCUSSION: We, therefore, conclude that hpaECMs has the potential to become an ideal platform for investigations aiming at the manufacturing of a regenerative medicine-inspired bioartificial endocrine pancreas

    Self-evaluation as a strategy of resistance to the ranking external evaluation

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    This article discusses the current meaning of the evaluation policies inand of school, presenting a study carried out by Brazilian and Portuguese researchers, with the participation of twenty public schools in the cities of São Paulo and Campinas (Brazil) and Porto (Portugal). Theoretically anchored in the Participatory Institutional Evaluation and Negotiated Quality approaches, the research involves the schools’ professionals and also sectors of education administration, through the study groups in each of the universities. The article critically addresses theexpertise function of the research that frequently legitimizes evaluations centered on products and thus lends credibility to standardized tests and to the proliferation of the so-calledevaluocracy, with consequent changes in the school inspection and management procedures, and also in the management of education systems. These changes corrupt/deform the concept of school autonomy and favor the proliferation of concession schools, stimulate the use of education vouchers, as well as the increase and naturalization of school inequalities and a certain representation of the Knowledge Society, which promotes vocational training for the working classes, recreating a dual education system. In contrast, this study argues for the possibilities of a virtuous circle between education, research and extension as a method of relation with public schools, starting from the concept of Negotiated Quality that, together with professionals and community in every school, initiates self-evaluation processes, with the intention of transformation and developing new relationships within and outside the school, reinforcing the strategic learning of a collective competence of social actors in favor of public school social quality.Este artigo discute o sentido atual das políticas de avaliaçãona e da escola ao apresentar a investigação realizada por pesquisadores brasileiros e portugueses, com a participação de vinte escolas públicas, nas cidades de São Paulo e Campinas (Brasil) e do Porto (Portugal). Referenciando-se na Avaliação Institucional Participativa e na Qualidade Negociada, a pesquisa se junta aos profissionais das escolas e de setores da administração educacional, com a formação de grupos de estudo em cada uma das universidades. O artigo aborda criticamente a função expertise da pesquisa que frequentemente legitima avaliações centradas nos produtos, portando credibilidade aos testes padronizados, à proliferação de uma avaliocracia, com consequente alteração de procedimentos de inspeção e direção escolares, além de mudanças na gestão dos sistemas educativos, corrompendo/deformando o conceito de autonomia escolar, favorecendo a proliferação de escolas administradas por concessão, o estímulo ao cheque-ensino, bem como o aumento e naturalização das desigualdades escolares e uma dada representação da sociedade do conhecimento, que refuncionaliza a formação profissional para as classes populares, recriando a dualidade do ensino. Em contraponto, a pesquisa argumenta as possibilidades de um circuito virtuoso do ensino, da pesquisa e da extensão como método na relação com escolas públicas, partindo de uma concepção de Qualidade Negociada que, em conjunto com profissionais e comunidade, em cada escola, inicia processos deautoavaliação, com intencionalidade de transformação e com a possibilidade de desenvolvimento de novas relações dentro e fora da escola, reforçando a aprendizagem estratégica da competência coletiva dos atores sociais em prol da escola pública de qualidade social

    Fósforo disponível de fosfato extraído de efluentes da suinocultura.

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    Apesar do papel de destaque no agronegócio, devido à importância econômica e social, a suinocultura é apontada como uma das principais atividades com maior potencial poluidor da pecuária brasileira, uma vez que produz elevada quantidade de efluente com alta concentração de nutrientes (principalmente o nitrogênio e fósforo), podendo causar desequilíbrio ambiental quando tais nutrientes são eliminados em grandes quantidades no ambiente. Objetivando minimizar os impactos causados pela falta de manejo e controle, os processos para remoção de fósforo têm sido amplamente estudados. A Embrapa Suínos e Aves tem trabalhado neste assunto buscando várias alternativas para redução destes impactos e, na medida do possível, agregar valor a estes resíduos, utilizando o Sistrates (Sistema de Tratamento de Efluentes da Suinocultura). Para remoção do fósforo é proposto um processo químico de extração usando hidróxido de cálcio (cal hidratada), como pós tratamento biológico, gerando um fosfato de cálcio, que pode ser utilizado como fertilizante ou como ingrediente na alimentação animal (FERNANDES, 2012). O fósforo é um dos componentes mais caros em rações para suínos e aves, um nutriente essencial quando do desenvolvimento de monogástricos, tendo em vista que está diretamente associado à formação óssea (80% do fósforo encontra-se na composição esquelética) e na utilização e transporte de energia e é de conhecimento geral que as atuais fontes de fósforo utilizadas são finitas, sendo a principal fonte suplementar o fosfato bicálcico, que é uma fonte mineral inorgânica (GARZILLO, 1996)

    Mesenchymal Stem Cells Secrete Multiple Cytokines That Promote Angiogenesis and Have Contrasting Effects on Chemotaxis and Apoptosis

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    We have previously shown that mesenchymal stem cells (MSC) improve function upon integration in ischemic myocardium. We examined whether specific cytokines and growth factors produced by MSCs are able to affect angiogenesis, cellular migration and apoptosis. Conditioned media (CM) was prepared by culturing MSC for 48 hours. CM displayed significantly elevated levels of VEGF, Monocyte Chemoattractant Protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and monokine induced by IFN-γ (MIG) compared to control media. MSC contained RNA for these factors as detected by RT-PCR. CM was able to induce angiogenesis in canine vascular endothelial cells. MCP-1 and MIP-1α increased cell migration of MSC while VEGF reduced it. H9c2 cells treated with CM under hypoxic conditions for 24 hours displayed a 16% reduction in caspase-3 activity compared to controls. PI 3-kinase γ inhibitor had no effect on controls but reversed the effect of CM on caspase-3 activity. MCP-1 alone mimicked the protective effect of CM while the PI 3-Kγ inhibitor did not reverse the effect of MCP-1. CM reduced phospho-BAD (Ser112) and phospho-Akt (Ser473) while increasing phospho-Akt (Thr308). MCP-1 reduced the level of phospho-Akt (Ser473) while having no effect on the other two; the PI 3-Kγ inhibitor did not alter the MCP-1 effect. ERK 1/2 phosphorylation was reduced in CM treated H9c2 cells, and inhibition of ERK 1/2 reduced the phosphorylation of Akt (Ser473), Akt (Thr308) and Bad (Ser112). In conclusion, MSC synthesize and secrete multiple paracrine factors that are able to affect MSC migration, promote angiogenesis and reduce apoptosis. While both MCP-1 and PI3-kinase are involved in the protective effect, they are independent of each other. It is likely that multiple pro-survival factors in addition to MCP-1 are secreted by MSC which act on divergent intracellular signaling pathways
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