147 research outputs found

    Observação do tempo sensível nas aulas do PIBID de geografia

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    Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014O objetivo deste trabalho é relatar de que forma o professor bolsista do PIBID pode instrumentalizar suas aulas de geografia, utilizando uma metodologia, útil, eficiente e barata. O assunto experimentado envolvia as discussões sobre as manifestações de tempo que acabam por definir modelos climáticos. A atividade prática consistiu na observação sensível do tempo, baseada na visualização sensitiva e interpretação de uma simbologia gráfica. As atividades foram desenvolvidas em 8 aulas, 2 para explicação do conteúdo e 6 para exposição da técnica e analises dos resultados. Os resultados obtidos demonstram que essa junção de pratica de observação fundamentada com uma excelente teoria, é capaz de despertar por parte dos alunos um grande interesse pelo assunt

    Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy

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    <p>Abstract</p> <p>Background</p> <p>Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies.</p> <p>Results</p> <p>A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1) retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US), BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12). Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival.</p> <p>Conclusion</p> <p>We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.</p

    Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment

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    Glioblastomas (GBMs) are high-grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12–15 months following standard therapy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR-specific affibody (ZEGFR:03115) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near-infrared light produces a cytotoxic response. ZEGFR:03115–IR700DX EGFR-specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter-Glo® assay, and in vivo using subcutaneous U87-MGvIII xenografts. In addition, mice were imaged pre- and post-PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor-dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the ZEGFR:03115–IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof-of-concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts

    The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

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    We present new measurements of cosmic microwave background (CMB) lensing over 94009400 sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at 2.3%2.3\% precision (43σ43\sigma significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of Alens=1.013±0.023A_{\mathrm{lens}}=1.013\pm0.023 relative to the Planck 2018 CMB power spectra best-fit Λ\LambdaCDM model and Alens=1.005±0.023A_{\mathrm{lens}}=1.005\pm0.023 relative to the ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination S8CMBL≡σ8(Ωm/0.3)0.25S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25} of S8CMBL=0.818±0.022S^{\mathrm{CMBL}}_8= 0.818\pm0.022 from ACT DR6 CMB lensing alone and S8CMBL=0.813±0.018S^{\mathrm{CMBL}}_8= 0.813\pm0.018 when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with Λ\LambdaCDM model constraints from Planck or ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} CMB power spectrum measurements. Our lensing measurements from redshifts z∼0.5z\sim0.5--55 are thus fully consistent with Λ\LambdaCDM structure growth predictions based on CMB anisotropies probing primarily z∼1100z\sim1100. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

    Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

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    Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe
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