102 research outputs found

    Refleksi Diri Sebagai Ide Dalam Penciptaan Seni Lukis

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    The purpose of this final project is to visualize several forms of self-reflection in telling personal experiences that become lessons. Self-reflection is the thing that is most attached to the writer's life when approaching the end of the lecture period. The idea of art is to visualize human figures as the subject of paintings that depict different body shapes. The method of realizing ideas is through the preparatory stage or the observation stage of the problems of concept realization or the creation of works of exhibition or display of works. The author presents 15 (fifteen) works of art through figures, all of which are different body shapes. The entire work was made using acrylic paint on canvas of the same size and was made in the year 2022

    Pengaruh Alat Bantu Penangkapan terhadap Hasil Tangkapan Alat Tangkap Purse Seine di Kecamatan Besuki Kabupaten Situbondo

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    Penelitian tentang pengaruh alat bantu penangkapan terhadap hasil tangkapan alat tangkap purse seine dilaksanakan di Kecamatan Besuki, Kabupaten Situbondo pada bulan September – Oktober 2012. Alat bantu yang digunakan berupa lampu, kombinasi rumpon dan lampu, dan tanpa menggunakan alat bantu. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh alat bantu terhadap hasil tangkapan dan pendapatan nelayan purse seine. Metode yang digunakan adalah eksperimen kuasi, sedangkan metode analisis data dengan cara Rancangan Acak Kelompok (RAK) dan menggunakan metode ANOVA serta uji Beda Nyata Terkecil (BNT). Hasil penelitian ini menunjukkan bahwa alat bantu penangkapan berpengaruh nyata terhadap hasil tangkapan nelayan purse seine. Alat bantu kombinasi rumpon dan lampu merupakan perlakuan terbaik untuk mendapatkan hasil tangkapan yang optimal. Alat bantu kombinasi rumpon dan lampu meningkatkan jumlah hasil tangkapan sebesar 21 % dibandingkan dengan alat bantu lampu, dan meningkatkan jumlah hasil tangkapan sebesar 34 % dibandingkan saat tanpa menggunakan alat bantu. Penggunaan alat bantu kombinasi rumpon dan lampu juga memberikan pendapatan terbesar dibandingkan dengan penggunaan alat bantu lampu dan tanpa menggunakan alat bantu

    Loss of SMAD4 Is Associated With Poor Tumor Immunogenicity and Reduced PD-L1 Expression in Pancreatic Cancer

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    Transforming Growth Factor β (TGFβ) is a key mediator of immune evasion in pancreatic ductal adenocarcinoma (PDAC), and the addition of TGFβ inhibitors in select immunotherapy regimens shows early promise. Though the TGFβ target SMAD4 is deleted in approximately 55% of PDAC tumors, the effects of SMAD4 loss on tumor immunity have yet to be fully explored. Using a combination of genomic databases and PDAC specimens, we found that tumors with loss of SMAD4 have a comparatively poor T-cell infiltrate. SMAD4 loss was also associated with a reduction in several chemokines with known roles in T-cell recruitment, which was recapitulated using knockdown of SMAD4 in PDAC cell lines. Accordingly, JURKAT T-cells were poorly attracted to conditioned media from PDAC cells with knockdown of SMAD4 and lost their ability to produce IFNγ. However, while exogenous TGFβ modestly reduced PD-L1 expression in SMAD4-intact cell lines, SMAD4 and PD-L1 positively correlated in human PDAC samples. PD-L1 status was closely related to tumor-infiltrating lymphocytes, particularly IFNγ-producing T-cells, which were more abundant in SMAD4-expressing tumors. Low concentrations of IFNγ upregulated PD-L1 in tumor cells in vitro, even when administered alongside high concentrations of TGFβ. Hence, while SMAD4 may have a modest inhibitory effect on PD-L1 in tumor cells, SMAD4 indirectly promotes PD-L1 expression in the pancreatic tumor microenvironment by enhancing T-cell infiltration and IFNγ biosynthesis. These data suggest that pancreatic cancers with loss of SMAD4 represent a poorly immunogenic disease subtype, and SMAD4 status warrants further exploration as a predictive biomarker for cancer immunotherapy

    Epidermal Growth Factor Receptor-Mediated Membrane Type 1 Matrix Metalloproteinase Endocytosis Regulates the Transition between Invasive versus Expansive Growth of Ovarian Carcinoma Cells in Three-Dimensional Collagen

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    Abstract The epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas and promotes cellular responses that contribute to ovarian cancer pathobiology. In addition to modulation of mitogenic and motogenic behavior, emerging data identify EGFR activation as a novel mechanism for rapid modification of the cell surface proteome. The transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) is a major contributor to pericelluar proteolysis in the ovarian carcinoma microenvironment and is subjected to extensive posttranslational regulation. In the present study, the contribution of EGFR activation to control of MT1-MMP cell surface dynamics was investigated. Unstimulated ovarian cancer cells display caveolar colocalization of EGFR and MT1-MMP, whereas EGFR activation prompts internalization via distinct endocytic pathways. EGF treatment results in phosphorylation of the MT1-MMP cytoplasmic tail, and cells expressing a tyrosine mutated form of MT1-MMP (MT1-MMP-Y 573 F) exhibit defective MT1-MMP internalization. As a result of sustained cell surface MT1-MMP activity, a phenotypic epithelial-mesenchymal transition is observed, characterized by enhanced migration and collagen invasion, whereas growth within three-dimensional collagen gels is inhibited. These data support an EGFR-dependent mechanism for regulation of the transition between invasive and expansive growth of ovarian carcinoma cells via modulation of MT1-MMP cell surface dynamics

    Long-Term Gemcitabine Treatment Reshapes the Pancreatic Tumor Microenvironment and Sensitizes Murine Carcinoma to Combination Immunotherapy

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    Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death with a median survival time of 6–12 months. Most patients present with disseminated disease and the majority are offered palliative chemotherapy. With no approved treatment modalities for patients who progress on chemotherapy, we explored the effects of long-term Gemcitabine on the tumor microenvironment in order to identify potential therapeutic options for chemo-refractory PDAC. Using a combination of mouse models, primary cell line-derived xenografts, and established tumor cell lines, we first evaluated chemotherapy-induced alterations in the tumor secretome and immune surface proteins by high throughput proteomic arrays. In addition to enhancing antigen presentation and immune checkpoint expression, Gemcitabine consistently increased the synthesis of CCL/CXCL chemokines and TGFβ-associated signals. These secreted factors altered the composition of the tumor stroma, conferring Gemcitabine resistance to cancer-associated fibroblasts in vitro and further enhancing TGFβ1 biosynthesis. Combined Gemcitabine and anti-PD-1 treatment in transgenic models of murine PDAC failed to alter disease course unless mice also underwent genetic or pharmacologic ablation of TGFβ signaling. In the setting of TGFβ signaling deficiency, Gemcitabine and anti-PD-1 led to a robust CD8+ T-cell response and decrease in tumor burden, markedly enhancing overall survival. These results suggest that Gemcitabine successfully primes PDAC tumors for immune checkpoint inhibition by enhancing antigen presentation only following disruption of the immunosuppressive cytokine barrier. Given the current lack of third-line treatment options, this approach warrants consideration in the clinical management of Gemcitabine-refractory PDAC

    Economics and finance of Small Modular Reactors: A systematic review and research agenda

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    The interest toward Small Modular nuclear Reactors (SMRs) is growing, and the economic competitiveness of SMRs versus large reactors is a key topic. Leveraging a systematic literature review, this paper firstly provides an overview of “what we know” and “what we do not know” about the economics and finance of SMRs. Secondly, the paper develops a research agenda. Several documents discuss the economics of SMRs, highlighting how the size is not the only factor to consider in the comparison; remarkably, other factors (co-siting economies, modularisation, modularity, construction time, etc.) are relevant. The vast majority of the literature focuses on economic and financial performance indicators (e.g. Levelized Cost of Electricity, Net Present Value, and Internal Rate of Return) and SMR capital cost. Remarkably, very few documents deal with operating and decommissioning costs or take a programme (and its financing) rather than a “single project/plant/site” perspective. Furthermore, there is a gap in knowledge about the cost-benefit analysis of the “modular construction” and SMR decommissioning

    Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading

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    <p>Abstract</p> <p>Background</p> <p>Squamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor.</p> <p>Methods</p> <p>In this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated.</p> <p>Results</p> <p>The T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma.</p> <p>Conclusion</p> <p>The results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis.</p
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