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Prior, J. Bruce. "Who Is "Full of Grace and Truth" in the Ws Text of John 1:14?" Bulletin for Biblical Research 11, nr 2 (1.01.2001): 233–38. http://dx.doi.org/10.2307/26422272.
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Abstract Authorities disagree in their readings of "full" in the Codex Washingtonianus text of John 1:14. The Alands, Swanson, and I opt for πληρη, whereas Sanders and Goodspeed read πληρις. If the former reading is correct, then the referent for the accusative masculine-singular adjective πληρη is still the Word, or Jesus Christ. If πληρις is the correct reading, however, then the crucial question is whether πληρις is merely an itacism for πλήρης or whether it is the same word as the plural adjective πλήρεις. If πληρις is plural, then the substitute scribe of Ws as well as the scribe of Codex Seidelianus and others understood that it is we rather than the Word who are "full of grace and truth."
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Prior, J. Bruce. "Who Is "Full of Grace and Truth" in the Ws Text of John 1:14?" Bulletin for Biblical Research 11, nr 2 (1.01.2001): 233–38. http://dx.doi.org/10.2307/26422272.
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Abstract Authorities disagree in their readings of "full" in the Codex Washingtonianus text of John 1:14. The Alands, Swanson, and I opt for πληρη, whereas Sanders and Goodspeed read πληρις. If the former reading is correct, then the referent for the accusative masculine-singular adjective πληρη is still the Word, or Jesus Christ. If πληρις is the correct reading, however, then the crucial question is whether πληρις is merely an itacism for πλήρης or whether it is the same word as the plural adjective πλήρεις. If πληρις is plural, then the substitute scribe of Ws as well as the scribe of Codex Seidelianus and others understood that it is we rather than the Word who are "full of grace and truth."
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Hickey, John, Garry Nolan, Markus Covert, Eran Agmon, Nina Horowitz i John Sunwoo. "180 T cell phenotype drives restructuring of tumor microenvironment to balance T cell longevity and tumor control: insights from multiplexed imaging and multi-scale agent based modeling". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (listopad 2021): A192. http://dx.doi.org/10.1136/jitc-2021-sitc2021.180.
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BackgroundImmune cell therapies continue to have success in treatment of cancers yet face challenges of complexity, cost, toxicity, and low solid-tumor efficacy. Much work has focused on the phenotype characterization and control of ex vivo expanded cells; however, little is known about its relationship to changes in the tumor microenvironment in vivo. Thus, we imaged tumors treated with different phenotype tumor-specific CD8+ T cells with CODEX multiplexed imaging1–4 that is able to visualize 42 antibodies at the same tissue in the tissue (figure 1A). To further probe this data in a systems immunology approach we created a multiscale agent-based model including critical circuits from the T cell-tumor microenvironment interactions (figure 1B).MethodsWe initialized our agent-based models various percentages of either PD1+, PD1-, PDL1+, or PDL1- phenotypes and ran simulations for 72 hours. We also treated PMEL CD8+ T cells with or without 2 hydroxycitrate as a metabolic inhibitor during activation to achieve different input phenotypes of CD8+ T cells for therapeutic adoptive transfer on day 10 following B16-F10 tumors had been established. We performed neighborhood analysis on CODEX multiplexed imaging data by clustering neighboring cell types using a sliding window for neighborhood analysis.ResultsInterestingly, the agent-based modeling indicated that the tumor phenotype switch to decrease proliferation was more effective than direct T cell killing. We observed spatially restricted inflammatory immune fronts when simulating with different initial percentages of PD1+ T cells and also from our CODEX multiplexed imaging. Quantitatively we observe that there is a drastic increase in the PDL1+, MHCI+, Ki67- tumor phenotype that increases with metabolically inhibited T cells. Neighborhood analysis indicated that metabolically treated T cells were able to create distinct immune cell environments that supported productive T cell-tumor interactions and also helped maintain T cell phenotype.ConclusionsThis indicates there is a balance for therapeutic T cell to mitigate chronic tumor exposure while controlling tumor growth through killing and by changing tumor phenotype. We observe T cells create distinct tumor microenvironments that differs significantly based on the starting T cell phenotype. Controlling T cell phenotype to promote productive immune-tumor structures will be critical to maintain T cell functionality and efficacy. In the future we will investigate T cell recruitment of immune structures by similar systems biology technologies.AcknowledgementsJ.W.H. is funded by an ACS Postdoctoral Fellowship (PF-20-032-01-CSM).ReferencesGoltsev Y, Samusik N, Kennedy-Darling J, Bhate S, Hale M, Vazquez G, Black S and Nolan GP, Deep profiling of mouse splenic architecture with CODEX multiplexed imaging. Cell, 174(4):968–981.Schürch CM, Bhate SS, Barlow GL, Phillips DJ, Noti L, Zlobec I, Chu P, Black S, Demeter J, McIlwain DR and Samusik N. Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front. Cell 182(5):1341–1359.Black S, Phillips D, Hickey JW, Kennedy-Darling J, Venkataraaman VG, Samusik N, Goltsev Y, Schürch CM. and Nolan GP. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nature Protocols 1–36.Kennedy-Darling J, Bhate SS, Hickey JW, Black S, Barlow GL, Vazquez G, Venkataraaman VG, Samusik N, Goltsev Y, Schürch CM and Nolan GP. Highly multiplexed tissue imaging using repeated oligonucleotide exchange reaction. European Journal of Immunology 51(5):1262–1277.Ethics ApprovalAll studies involving mice were approved under Stanford’s APLAC protocol 33502.
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Argın, Sanem, i Sibel Şimşek Yazıcı. "Türkiye’de Üretilen Mısırlarda Mikotoksin Düzeylerinin ve GDO Varlığının Araştırılması". Turkish Journal of Agriculture - Food Science and Technology 7, nr 1 (14.01.2019): 54. http://dx.doi.org/10.24925/turjaf.v7i1.54-60.2108.
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In Turkey, there is a continuous increase in the annual production of corn. Nevertheless, consumers’ perception of corn becomes more negative each day, since corn is the most genetically modified product worldwide, after soybean. While the potential negative effects of genetically modified corn are being debated, the greatest threat to human health in corn is the presence of mycotoxins. In this study, corn samples were collected from 634 fields in 552 villages of 24 cities in Turkey, and the presence of GMO, aflatoxin B1, total aflatoxins, fumonisin B1, fumonisin B2, T-2 toxin, HT-2 toxin, zearalenone and deoxynivalenol was investigated. No transgenic element was found in any of the corn samples. The total aflatoxin levels of the corn samples were found to be below the Turkish Food Codex limit and, among the total of 634 samples, only one sample exceeded the Turkish Food Codex limit for aflatoxin B1. Moreover, no T-2 toxin, HT-2 toxin, zearalenone and deoxynivalenol were detected in the samples. The total amounts of fumonisins were also found to be below the Turkish Food Codex limit. These results show that domestically produced corn meets the standards for food safety.
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Xu, Mina, Stephanie Halene, Rong Fan i Archibald Enninful. "Spatial Multiomics Profiling of Angioimmunoblastic T-Cell Lymphoma". Blood 142, Supplement 1 (28.11.2023): 6109. http://dx.doi.org/10.1182/blood-2023-190647.
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Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of non-Hodgkin lymphoma (NHL) characterized primarily by a T follicular helper cell (TFH) phenotype. AITL presents with a highly complex tumor microenvironment with the tumor cells on a scaffold of highly arborized CD21+ follicular dendritic cells found in proximity to high endothelial venules (HEVs). The organized structure of the lymph node with distinct B cell and T cell zones is disrupted in the lymph node samples from patients with AITL. Lymphoid follicles in most AITL cases tend to be depleted, not hyperplastic as in other lymphomas. AITL tumor cells express CD10, BCL6, PD1, CXCL13, C-X-C motif chemokine receptor 5 (CXCR5), ICOS, and signaling lymphocytic activation molecule-associated protein (SAP) with diagnosis based on the expression of at least 2 of these markers. Our study uses novel spatial omics technology (Deterministic Barcoding in Tissue (DBiT-seq) and multiplexed immunofluorescence staining (CODEX)) to fully characterize the transcriptional and proteomic landscape of AITL. Methods: In this study, initial FFPE biopsy specimens from 22 patients with AITL were collected from archives. 10 µm thick tissue sections on poly-L-lysine coated slides were prepared for the performance of multiplexed immunofluorescence imaging (CODEX) for 12 immune-related markers: Podoplanin, CD20, CD4, CD8, CD68, CD45RO, CD3e, GranzymeB, PD1, Ki67, CD21 and CD34 using the PhenoCycler-Fusion system. We also validated anti-EBV Latent Membrane Protein 1 antibody. Cell segmentation was performed using a Stardist-based model in QuPath and downstream analysis done using the Seurat package. On an adjacent tissue section, we used Spatial CITE-seq to co-map the whole transcriptome and ~160 proteins. Results: From the multiplexed immunofluorescence staining, we observed CD21+ Follicular dendritic cells in close proximity to HEVs as expected from the spatial architecture of AITL. We also found 11 spatially distinct clusters differentially expressing the marker proteins. We observed a lower number of CD8+ cytotoxic T cells relative to CD4+ Helper T cells. We also identified cellular neighborhoods and their composition found a population of FDCs that directly interact with the tumor cells. From spatial CITE-seq, we average of ~670 genes were found in each spot. We also found the expression of CXCL13, TET2, DNMT3A and PDCP1 which are markers associated with AITL. There was a strong correlation between the transcript signals detected in Spatial CITE-seq and the protein expression from CODEX. Conclusions: Our study revealed the spatial organization of the tumor microenvironment of AITL. We envision that combining multiplexed immunofluorescence and Spatial CITE-seq will further our understanding of the AITL tumor environment and could lead to the discovery of novel clinical targets.
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Jung, Wulf-Ingo, Otto Lutz i Markus Pfeffer. "Localized NMR Spectroscopy with a 1.5 T Whole- Body Imager Using CODEX". Zeitschrift für Naturforschung A 46, nr 5 (1.05.1991): 401–4. http://dx.doi.org/10.1515/zna-1991-0504.
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AbstractWith a whole-body NMR imager working at 1.5 T localized 1H and 31P spectra were obtained using the CODEX sequence. Examples are presented: With ethanol 'H spectra the resolution, stability, and sensitivity are documented. Human in vivo investigations of the yellow bone marrow of (13 mm)3 volume elements show well resolved spectra with a good signal-to-noise ratio. An example for 31P spectroscopy is also given
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Jung, W. I., i O. Lutz. "Volume Selective NMR Spectroscopy by Coded Slice Excitation (CODEX)". Zeitschrift für Naturforschung A 43, nr 11 (1.11.1988): 909–13. http://dx.doi.org/10.1515/zna-1988-1101.
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Abstract A method for volume selective nuclear magnetic resonance spectroscopy has been developed and implemented on an 1.5 T whole body imager for in vivo investigations. Four single experiments produce different magnetizations in the same slice, and a special subtract scheme yields the signal of only the volume of interest, which is accurately defined. The resolution of the spectra and the stability of the method have been verified with a water phantom containing acetone, ethanol, methanol, and oil vessels.
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Baertsch, Marc-Andrea, Alexander Brobeil, John Hickey, Maximilian Haist, Alexandra Maria Poos, Guolan Lu, Wilson Kuswanto i in. "Spatial Dissection of the Bone Marrow Microenvironment in Multiple Myeloma By High Dimensional Multiplex Tissue Imaging". Blood 142, Supplement 1 (28.11.2023): 85. http://dx.doi.org/10.1182/blood-2023-189255.
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Introduction Multiple myeloma (MM) is shaped by interactions between immune, stromal and tumor cells in the bone marrow (BM) microenvironment (BMME). Our understanding of these processes is based on high parametric flow cytometry and single cell transcriptomics, which lack spatial resolution. Thus, crucial aspects of the in situ tumor ecosystem, including cell-cell interactions, can only be predicted. Novel high dimensional, multiplex tissue imaging methods are able to capture similar granularity while also preserving spatial organization. By optimizing antibody selection, as well as staining, imaging and data processing protocols we have established a BMME-targeted CODEX workflow based on a 60 marker panel. Here, we conducted the first comprehensive multiplex protein imaging survey of the BMME across the spectrum of MM and precursor stages and leveraged paired FISH and whole genome sequencing (WGS) to elucidate the interplay of tumor intrinsic features and the BMME. Methods We imaged 489 BM trephine biopsies in tissue microarray format on the CODEX (Akoya Biosciences) platform. After quality control (≥750 cells per core, <25% unclassifiable cells) we retained data from 12 non-malignant controls, 13 MGUS, 20 smoldering MM, 349 uniformly treated newly diagnosed MM (NDMM) patients from a phase III clinical trial, as well as 22 relapsed MM samples with a median of 3 (range 1-6) tissue cores per sample, comprising a total of 3.1 million single cells. CODEX data was processed and analyzed using custom scripts. Cellular neighborhoods were computed by clustering the cell type composition of sliding windows (n=10 nearest neighboring cells) across the tissue. WGS (n=212) and FISH (n=309) were performed on CD138-purified BM mononuclear cells and analyzed using in-house pipelines. Results We identified 40 cell types, encompassing the relevant lineages (myeloid, lymphoid, stromal, endothelial, tumor), subtypes (e.g. T, B, NK cells) and functional states (e.g GRZB, Ki67, and PD1) of the BMME. The degree of plasma cell infiltration determined by CODEX correlated with the clinical pathologist's quantification based on classical immunohistology (r=0.77, p<0.0001), and the kappa/lambda status of MM cells matched the reported light chain restriction, supporting the validity of our data. At the compositional level, we observed shifts in relative cell type abundance from precursor to MM stages. Major changes in the BMME included enriched stromal, endothelial and CD8+ T cells as well as depleted polymorphonuclear (PMN), erythropoietic and CD4+ T cells in advanced stages. The highest proportion of monocytoid dendritic cells, monocytes, mast cells and cytotoxic CD8+ T cells was seen in relapsed MM. Leveraging the spatial resolution of the CODEX data, we identified multiple distinct cellular neighborhoods (CNs) defined by recurrent local cell type composition. CNs enriched for plasma cells in combination with different immune cell subsets including exhausted T cells increased towards the MM stage, while CNs dominated by PMNs, erythropoietic cells and CD206 negative macrophages decreased. To investigate links between MM subtypes and BMME patterns, we correlated CODEX data with MM-initiating and driver events. While patients with t(4;14) showed a significant increase in eosinophils, patients with gain1q had higher levels of endothelial and stromal subsets colocalizing in the same CN. Distinct types of stromal cells were also enriched in patients with double hits (≥2 FISH high risk features). RAS mutations and biallelic inactivation of tumor suppressor genes were associated with altered T cell subset composition. Further corroborating the importance of BMME architecture, a CN with colocalization of plasma and exhausted CD8 T cells was associated with unfavorable prognosis in NDMM patients. Conclusions High dimensional, multiplex tissue imaging of the BMME enables interrogation of cellular interactions and tissue architecture in situ in clinical samples at single cell resolution. To our knowledge this is the first highly multiplexed spatial study of the human BMME in a large clinical cohort and the first such study in multiple myeloma. We track characteristic shifts in tissue composition associated with disease progression, reveal genotype-phenotype associations in the BMME as a correlate of tumor-microenvironment co-evolution and detect prognostically relevant tissue architectural features.
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Pinheiro, Paulo José Moraes. "Sobre o manuscrito Alfa da Poética de Aristóteles (Parisinus Gr. 1741)". O que nos faz pensar 27, nr 42 (30.06.2018): 47. http://dx.doi.org/10.32334/oqnfp.2018n42a594.
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Dos manuscritos da Poética de Aristóteles que chegaram aos nossos dias, na condição de fonte primária subsistente (codd.), temos apenas dois textos gregos (o que consta no codex Parisinus Graecus 1741 (=A), proveniente do séc. X/XI, e o que consta no codex Riccardianus 46 (=B), do séc. XII), a tradução latina de G. de Moerbeke (codices Etonensis 129 (=O), de 1300, e Toletanus bibl. Capit. 47.10 (= T), de 1280), e a tradução árabe de Abu-Bishr Matta, feita a partir da tradução siríaca desaparecida. O que pretendo, nesse artigo, é descrever o percurso do assim chamado Manuscrito Alfa da Poética de Aristóteles, ou seja, a que consta no codex Parisinus Graecus 1741 entre as páginas 184 e 199. Pretendo ainda fazer alusão à importância de um estudo sobre as condições em que se dá a apreensão do texto antigo. De fato, a leitura que fazemos hoje da Poética é composta da variação de sentido inerente ao entendimento, o que é óbvio, e da variação, muitas vezes sutil e, via de regra, determinante, do que foi efetivamente escrito, há tantos séculos, com o estilete de um ou outro escriba.
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Delgado-Gonzalez, Antonio, Kenyi Donoso, Maximilian Haist, Veronica D. Gonzalez, Ying-Wen Huang, Brooke E. Howitt, Garry P. Nolan, Katherine Fuh i Wendy J. Fantl. "Abstract B061: Multiparametric single-cell characterization of the immune tumor microenvironment in ovarian carcinomas". Cancer Research 84, nr 5_Supplement_2 (4.03.2024): B061. http://dx.doi.org/10.1158/1538-7445.ovarian23-b061.
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Abstract Tubo-ovarian high-grade serous carcinoma (HGSC) has an overall 5-year survival rate of ~50%. Standard-of-care treatment is surgical debulking followed by platinum-based chemotherapy. Initially, most women respond, but eventually, most (~80%) will relapse within 5 years. Nevertheless, for women with tumors for whom upfront debulking surgery is not possible, neoadjuvant chemotherapy (NACT) with interval debulking surgery followed by chemotherapy is an alternative. Cancer immunotherapy, an alternative treatment modality, drives an anti-tumor immune response. Immunotherapy approaches targeting a patient’s T cells have shown remarkable success for a variety of malignancies. Unfortunately, HGSC is largely unresponsive. In a previous study, we applied mass cytometry to newly diagnosed HGSC tumors to characterize intra-tumoral T and natural killer (NK) cells. We identified intra-tumoral decidual-like (dl)-NK cells that were positively correlated with tumor cell and transitioning epithelial-mesenchymal cell abundance. Decidual NK cells comprise 70% of lymphocytes during the first trimester of pregnancy and have a critical immune tolerant role in preventing a mother-to-be from rejecting her hemi-allogenic fetus. dl-NK cells, like their decidual counterparts, are distinguished from other NK cell phenotypes by the expression of the tetraspanin CD9. In vitro data demonstrated that CD9 endowed NK cells with immune-suppressive functions (attenuated cytotoxicity and reduced anti-tumor cytokine production). This study also revealed that in four out of ten patient-matched HGSC samples pre- and post-NACT, chemotherapy induced a more immune-suppressive immune tumor microenvironment (iTME). These data led to our hypothesis that the spatial architecture of the HGSC iTME, specifically encompassing cellular neighborhoods (CNs) comprising dl-NK and T cells, will predict response to platinum-based chemotherapy. Thus, we have applied CO-Detection by indEXing (CODEX), a highly-multiplex single-cell proteomic imaging technology, to comprehensively characterize the iTME of HGSC tumors. By measuring ~60 markers per tissue section at a resolution of <400 nm, CODEX generates proteomic co-expression information to deeply phenotype individual cells while preserving their spatial coordinates and relationships within the HGSC iTME. We have developed and validated a CODEX antibody panel targeting tumor, stroma and immune cells, NK cells receptors and ligands, and proteins specific for decidual NK cells, for formalin-fixed paraffin-embedded tissues. We developed and validated a panel comprised of 57 CODEX antibodies to image the iTME of 14 HGSC tumors, 7 matched before- and after-NACT. Our continuing data analyses will identify the spatial features of cellular neighborhoods enriched for dl-NK and T-cells to gain insight into their role in disease progression and treatment outcomes. In conclusion, we used CODEX, a highly multiplex single-cell imaging platform to deeply characterize the cellular architecture of the iTME in HGSC tumors before and after NACT. Citation Format: Antonio Delgado-Gonzalez, Kenyi Donoso, Maximilian Haist, Veronica D Gonzalez, Ying-Wen Huang, Brooke E. Howitt, Garry P. Nolan, Katherine Fuh, Wendy J. Fantl. Multiparametric single-cell characterization of the immune tumor microenvironment in ovarian carcinomas [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B061.
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Shekhar, Soumya, Vaibhav Sahai, Kathryn Howe, Qingfeng Zhu, Aya Kondo, Helen L. Fedor, Valerie Gunchick i in. "Deep immune profiling of intrahepatic cholangiocarcinoma with CODEX multiplexed imaging." Journal of Clinical Oncology 42, nr 16_suppl (1.06.2024): 4117. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.4117.
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4117 Background: Intrahepatic cholangiocarcinoma (iCCA) is subclassified by the presence or absence of potentially actionable molecular alterations, of which IDH1 mutations and FGFR2 fusions and rearrangements are most frequently observed. Little is known about the relationship between molecular features of iCCAs and the tumor immune microenvironment (TME). Methods: We performed a high-parameter immune phenotyping of the TME of FGFR2 fusion/rearrangement positive (FGFR2+), IDH1 mutation positive (IDH1+), and FGFR2/IDH1 wild type iCCA samples at the single-cell level using CO-Detection by indEXing (CODEX). Neighborhood analysis was based on a k-nearest-neighbors approach followed by k-means clustering to identify the spatial location of each cell type and their proximity to one another. Simplified spatial networks specific to molecular subtypes were generated based on the shortest Euclidean distances from any given cell to all other cell types. Results: A total of 24 tumors were examined (n=7 FGFR2+, n=9 IDH1+, n=8 other). Compared to other molecular subtypes, FGFR2+ tumors had an immune-desert phenotype characterized by a reduced abundance of CD8+ T cells (p < 0.05), CD117+ mast cells (p < 0.05), and CD68+/CD163+ macrophages (p < 0.05) but with an increased number of CD11b+/CD15+ granulocytes (p < 0.05). IDH1+ tumors were characterized by a decreased amount of CD11b+/CD15+ granulocytes (p < 0.05) when compared to other subtypes. In terms of spatial analysis, CD4+ T cells were located further from tumor cells in FGFR2+ iCCA compared to IDH1+ iCCA (p < 0.05) and other molecular subtypes (p=0.05). In contrast, CD11b+/CD15+ granulocytes were located closer to tumor cells in FGFR2+ tumors (p < 0.05). Additionally, closer neighbor proximity between CD4+ T cells and CD11b+/CD15+ granulocytes was observed in FGFR2+ tumors compared to both IDH1+ tumors (p < 0.05) and other tumor subtypes (p = 0.05), indicating a stronger lymphoid–myeloid neighboring relationship in the TME of FGFR2+ iCCA. Conclusions: FGFR2+ and IDH1+ iCCAs have distinct immunophenotypes, providing initial evidence that molecular alterations may inform the selection of patients for immunotherapy. Both the quantity of immune cells as well as the spatial relationships between immune cells may influence iCCA prognosis and response to therapy. Tailoring immunotherapeutic approaches to specific molecular subsets may improve outcomes across the divergent molecularly defined iCCA subtypes.
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Pouderon, Bernard. "Note Critique Sur Le Codex Parisinus Graec. B.N. 1555 a. La Pseudo-Histoire Ecclésiastique De Basile De Césarée Et Les Quaestiones Attribuées à Grégoire De Nazianze". Vigiliae Christianae 52, nr 2 (1998): 204–6. http://dx.doi.org/10.1163/157007298x00119.
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AbstractLe codex Parisinus Graecus B.N. 1555 A est un codex de papier de 10 + 194 folios, écrit en minuscule mêlées de quelques onciales sur deux colonnes de 29 lignes; il est généralement daté des XIIIe-XIVe siècles. Il a été décrit par H. Omont dans son Inventaire sommaire des manuscrits grecs de la Bibliothèque nationale, t. 2, Paris, 1888, pp. 93-94; sa description peut être complétée par celle de G. Hansen dans son édition de Théodore le Lecteur: Theodoros Anagnostes Kirchengeschichte, Berlin, 1971, pp. XXV-XXVI.1 Son contenu, très hétérogène, est soigneusement décrit par H. Omont; nous ne reviendrons pas sur son relevé. Mais, au sein de cette collection disparate, quelques feuillets ont attiré notre attention. En effet, du folio 167v au folio 178v, on trouve les fragments ou l'épitomè d'une "Histoire ecclésiastique" attribuée à saint Basile.
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Shekarian, Tala, Anna Theresa Wachnowicz, Julia Flammer, Chiara Paganetti, Tomas Martins, Manuele Muraro, Christian Martijn Schürch i Gregor Hutter. "ATIM-48 (LTBK-05). MULTIDIMENSIONAL PERSONALIZED RESPONSE ASSESSMENT TO MICROGLIA MODULATORS IN GLIOBLASTOMA BIOREACTORS". Neuro-Oncology 21, Supplement_6 (listopad 2019): vi284. http://dx.doi.org/10.1093/neuonc/noz219.1198.
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Abstract BACKGROUND Recently, strategies harnessing the non-neoplastic immune tumor microenvironment (iTME), consisting of macrophages and microglia (TAMs), as well as adaptive immune cells have been employed to treat glioblastoma (GBM). To evaluate the effect of local TAM-modulating therapies in combination with T-cell checkpoint inhibitors, we generated 3D GBM perfusion bioreactor cultures from patient-derived samples. We report patient- and tumor region specific responses to microglia modulators and checkpoint inhibitors using multidimensional fluorescent microscopy techniques, and multiplexed cytokine measurements, Subsequently, we aime at identifying responders versus non-responders as well as predictive markers of treatment response. METHODS Fresh, neuronavigated GBM biopsies from tumor center and periphery were placed into perfusion bioreactors and cultured for 7 days. Explants were treated with combinations of TAM and T-cell modulating drugs including anti-PD1 and anti-CD47 antibodies and their combination. Tissue was harvested for histology, and supernatants were processed for multiplexed cytokine analysis. Multidimensional CODEX technology analysis using a customized TAM centric 54 marker panel was implemented, and a map of individualized response criteria to specific immunotherapies developed. RESULTS Multiplex cytokine analysis showed a dominance of proinflammatory cytokines (CCL2, CCL3, CCL4 and PAI-1) in the periphery of the tumor at baseline. We further observed that the tumor periphery was more responsive to treatments confirming the efficacy of the treatment after tumor resection. Using CODEX, we identified specific cell types responding to the treatment and undergoing phenotypic changes. Moreover, dynamic shifting of T-cell checkpoint expression levels under treatment pointed to potential resistance mechanisms in a subset of tumors. Further, we identified region-specific cytokine release as a response to the treatment in a series of 8 patient-specific explant cultures. In summary, we present an in-depth profiling of the GBM-region specific iTME at baseline and document its dynamic response under innate/adaptive immune modulators using CODEX. CONCLUSION The proposed approach serves as a patient-tailored ex vivo “Clinical Trial” by stratifying the individual patient’s iTME response.
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Parsons, P. J. "The Codex - C. H. Roberts, T. C. Skeat: The Birth of the Codex. Pp. ix + 78;, 6 plates. London: The British Academy, 1983. £13." Classical Review 37, nr 1 (kwiecień 1987): 82–84. http://dx.doi.org/10.1017/s0009840x00100459.
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CHARLESWORTH, S. D. "T. C. Skeat, [prod ]64+67 and [prod ]4, and the Problem of Fibre Orientation in Codicological Reconstruction". New Testament Studies 53, nr 4 (6.09.2007): 582–604. http://dx.doi.org/10.1017/s002868850700029x.
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Because of the uniformity of the text, NT papyri are well suited to codicological reconstruction. If there are two or more pieces of papyrus from the same codex, sound reconstructions are often possible. But good methodology will account for the fibre orientation of the fragments. Flawed conclusions are the inevitable result of neglecting such analysis. Skeat erred in this direction as regards [prod ]64+67 and [prod ]4. Nevertheless, his contribution in the area was substantial and enduring. It only remains for scholars to appreciate the insights that codicology can bring to the study of the NT text.
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Albrecht, Felix. "Neu entdeckte Traktate des (Ps.-)Amphilochius von Ikonium in Unzialschrift". Vigiliae Christianae 66, nr 3 (2012): 283–86. http://dx.doi.org/10.1163/157007212x617272.
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Abstract Codex Bodleianus Auct. T. 4. 21 (Misc. 259) is a 12th-century manuscript written in large part on palimpsested parchment. It contains, inter alia, hitherto unknown treatises of (Ps.-)Amphilochius Iconiensis as underlying scripture (scriptio inferior). In 2011 the author discovered these treatises during a research stay at the Bodleian Library in Oxford. The (Ps.-)Amphilochius sections are written in a clear uncial script from the 8th-9th century. A complete edition of the manuscript’s scriptiones inferiores together with a codicological analysis and a palaeographical description is in preparation.
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Shekarian, T., A. Wachnowicz, J. Flammer, C. Paganetti, T. Martins, M. Muraro, C. Schürch i G. Hutter. "P12.09 Multidimensional Personalized Response Assessment to Microglia Modulators in Gioblastoma Bioreactors". Neuro-Oncology 21, Supplement_3 (sierpień 2019): iii61. http://dx.doi.org/10.1093/neuonc/noz126.220.
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Abstract BACKGROUND Recently, strategies harnessing the non-neoplastic, immune tumor microenvironment (iTME) consisting of myeloid-derived macrophages and yolk sac derived microglia (termed TAMs) as well as adaptive immune components have been employed to treat glioblastoma (GBM). To evaluate the effect of TAM-modulating therapies in combination with T-cell checkpoint inhibitor approaches, we generated 3D GBM bioreactor cultures from patient-derived samples. Here, we report patient-tailored, tumor region specific response assessment to microglia modulators and T-cell checkpoint inhibitors using multidimensional fluorescent microscopy techniques MATERIAL AND METHODS GBM tissue fragments from the tumor center and periphery were placed into perfusion bioreactors shortly after resection and cultured for up to 3 weeks. Control conditions included non-perfused cultures of the same tissue. Cultures were treated with combinations of TAM and T-cell modulating, FDA approved drugs including anti-PD1, anti-CTLA4 and anti-CD47 antibodies. Tissue was harvested for histology, RNA extraction, and supernatants were processed for multiplexed cytokine analysis. Multidimensional CODEX technology analysis using a customized TAM/microglia-centric 50 marker panel was implemented, and a map of individualized response criteria to specific immunotherapies developed. RESULTS We were able to cultivate viable GBM tissue with intact iTME. Tumor cell proliferation and invasion capacity were preserved for up to 3 weeks. Conventional immunohistochemistry confirmed the presence of TAMs and T cells. Treatment with immunomodulators resulted in a profound polarization shift of TAMs. Furthermore, cytokine analysis confirmed proinflammatory immune responses in most assessed samples. We present preliminary data of the CODEX analysis of our combinatorial immunotherapies in a series of 8 patient-specific explant samples. CONCLUSION GBM tissue could be incubated in the perfused 3D bioreactor model and kept viable for up to 21 days. The proposed model allows patient-tailored testing of immunomodulatory drugs by taking into account the patients individual iTME response. GBM tissue could be incubated in the perfused 3D bioreactor model and kept viable for up to 21 days. The proposed model allows patient-tailored testing of immunomodulatory drugs by taking into account the patients individual iTME response.
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Dubovský, Peter. "Foreign Women Transforming Elijah into the Prophet of the Lord (1 Kgs 17–19)". Biblical Annals 14, nr 1 (30.01.2024): 1–16. http://dx.doi.org/10.31743/biban.15952.
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This paper analyses the different versions of the Elijah cycle (1 Kgs 17–19) as witnessed, in particular, in the Masoretic text (MT), the Codex Vaticanus (GB), the Codex Alexandrinus (GA), and the Antiochian text (GAnt.). The comparison of the manuscripts shows that the MT adds and omits certain words and expressions. The author explored whether the additions and omissions are scribal mistakes or rather an intentional redactional intervention. Arguing for the latter, the author proposes that the MT presents not only the great deeds of the great prophet Elijah but also how Elijah became such a great prophet. Based on this analysis, the author proposes five stages of Elijah’s formation process: 1 . t he transformation of a man into a listener (1 Kgs 17:2–6); 2. Elijah’s transformation into a man of God’s word (the Cherith episode and the Zarephath episode in 17:7–16); 3. the transformation from a man of God’s word into a man of God (the resuscitation of the dead son in 17:17–24); 4. the transformation from a man of God into a prophet (the Carmel episode 18:1–40); 5. the transformation of a zealous prophet into a man standing before the Lord (19:1–18).
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Xia, Yihan, Junrui Ma, Xiaobao Yang, Danping Liu, Yujie Zhu, Yanan Zhao, Xuefeng Fei, Dakang Xu i Jing Dai. "Identifying the Spatial Architecture That Restricts the Proximity of CD8+ T Cells to Tumor Cells in Pancreatic Ductal Adenocarcinoma". Cancers 16, nr 7 (7.04.2024): 1434. http://dx.doi.org/10.3390/cancers16071434.
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The anti-tumor function of CD8+ T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+ T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+ T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+ T and CD4+ T cell-enriched neighborhoods enriched the majority of CD8+ T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+ T cells in this spatial architecture were significantly closer to themselves and the CD4+ T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+ T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.
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Ruf, Benjamin, Noemi Kedei, Matthias Bruhns, Sepideh Babaei, Bernd Heinrich, Varun Subramanyam, Chi Ma i in. "Abstract 2106: Spatially resolved immune cell atlas of human liver cancer identifies the cellular interaction network underlying mucosal-associated invariant T (MAIT) cell dysfunction in hepatocellular carcinoma". Cancer Research 82, nr 12_Supplement (15.06.2022): 2106. http://dx.doi.org/10.1158/1538-7445.am2022-2106.
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Abstract Introduction: Hepatocellular Carcinoma (HCC) is considered a prototype of inflammation-derived cancer arising from chronic liver injury. The cellular composition of the HCC tumor immune microenvironment (TiME) has a major impact on cancer biology as the TiME can influence tumor initiation, progress, and response to therapy. Mucosal-associated invariant T (MAIT) cells can represent the most abundant T cell subtype in the human liver and have been found to be impaired in both number and function in liver cancer. These innate-like T cells are assigned crucial roles in regulating immunity and inflammation in the context of infection, albeit their role in HCC remains elusive. Methods: High-dimensional flow cytometry was used to analyze MAIT cell phenotypic changes in murine and human liver cancer. Highly multiplexed immunofluorescence microscopy was used to quantify immune cell infiltration in primary human HCC samples. We developed and validated a comprehensive 37-plex antibody panel for immunofluorescence imaging of human fresh frozen HCC samples. We applied co-detection by indexing (CODEX) technology to simultaneously profile in situ expression of 37 proteins at sub-cellular resolution in 15 HCC patient samples using whole slide scanning. Initial image analysis was performed using HALO quantitative image analysis software. Finally, we established an image analysis pipeline to quantify the MAIT cell interaction network at the HCC invasive front. Results: Profiling of human and murine HCC using flow cytometry and highly multiplexed CODEX imaging revealed substantial dysregulation/aberrant activation of MAITs in liver cancer. In situ phenotyping of 4,500,000 single cells (including 1,500,000 CD45+ immune cells) allowed for the quantification of 20 distinct immune cell phenotype clusters, differential analysis of activation markers and spatial features of each individual cell. CODEX imaging revealed detailed composition of the MAIT cell niche in human liver cancer tissue allowing for further distinct spatial analysis including infiltration and nearest-neighbor analysis. Importantly, flow cytometry data of paired samples correlated well with image-based immune phenotyping. Beyond that, whole slide imaging revealed spatial relationships and interactions within the MAIT cell hub localized in distinct tissue regions. Conclusion: Here, we demonstrate that spatially resolved, single-cell analysis of human liver cancer tissue allows for in-depth characterization of interacting immune cellular programs underlying MAIT cell dysfunction in HCC. Citation Format: Benjamin Ruf, Noemi Kedei, Matthias Bruhns, Sepideh Babaei, Bernd Heinrich, Varun Subramanyam, Chi Ma, Simon Wabitsch, Benjamin Green, Kylynda C. Bauer, Yuta Myojin, Jonathan Qi, Amran Nur, Justin McCallen, Layla Greten, William G. Telford, Merrill K. Stovroff, Kesha Oza, Jiman Kang, Alexander Kroemer, Manfred Claassen, Firouzeh Korangy, Tim F. Greten. Spatially resolved immune cell atlas of human liver cancer identifies the cellular interaction network underlying mucosal-associated invariant T (MAIT) cell dysfunction in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2106.
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Ruf, Benjamin, Vanessa Catania, Noemi Kedei, Simon Wabitsch, Chi Ma, Laurence Diggs, Qianfei Zhang i in. "693 Mucosal-associated invariant T (MAIT) cell regulation networks in anti-tumor immunity". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (listopad 2021): A721. http://dx.doi.org/10.1136/jitc-2021-sitc2021.693.
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BackgroundMAIT cells are MR1-restricted innate-like T cells that recognize non-peptide antigens including riboflavin derivates. They account for up to 10 % of circulating T cells, but they are further enriched at mucosal sites and the liver. On one hand, altered MAIT number and function have been reported in liver cancer with MAITs correlating with poor clinical outcome. On the other hand, we recently demonstrated that MAIT cells can potentially have anti-tumor activity suggesting them as a novel target for cancer immunotherapy. Yet, the cellular and humoral factors that determine MAIT cell fate in the context of malignancies remain largely unknown.MethodsHighly multiplexed immunofluorescence-based CODEX imaging and high-dimensional flow cytometry was used to analyze MAIT cell infiltration and phenotype in human HCC samples. We recently developed an experimental framework to manipulate MAIT cells in vivo using VitaminB2 synthesis pathway-derived antigen 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) in combination with Toll-like receptor 9 agonist CpG. Next, we used murine models of orthotopic primary liver cancer and liver metastasis across two different mouse strains, to assess anti-tumor activity of MAIT cells. A series of pharmacological depletion experiments and genomic knockout mouse strains were used to identify additional effector immune cells and humoral factors mediating the anti-tumor effect.ResultsUsing flow cytometry and spatially resolved analysis of multiplexed CODEX microscopy images, we found impaired infiltration and altered phenotype of MAIT cells in human HCC tumors compared to unaffected liver tissue. Thus, we sought out to experimentally increase MAIT cell infiltration into liver cancers using murine models. Co-administration of 5-OP-RU + CpG induced a strong systemic in vivo expansion and activation of MAIT cells with Th1/NK-like polarization. We found MAIT cells to be potent orchestrators of anti-tumor function in vivo when activated by a combination of 5-OP-RU + CpG. MAIT-directed 5-OP-RU/CpG showed pronounced and consistent anti-tumor activity against different models of liver cancer and prolonged mouse survival. Importantly, such tumor inhibition was absent in MAIT-deficient MR1 k.o. mice but nor dependent on MR1 expression on tumor cells. Additional pharmacological depletion studies/genomic k.o. models helped to identify antigen presenting cells, downstream effector cells as well as co-stimulatory cytokines as critical components needed for MAIT-induced tumor suppression.ConclusionsMAIT cells are important players in cancer immunology and represent an attractive novel target for cancer immunotherapy. Fine-tuned, context-dependent mechanisms determine MAIT-cell fate in vivo as they undergo a phenotypic switch upon 5-OP-RU and CpG treatment enabling them to exert potent anti-tumor function.
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Schreiner, Peter. "Briga o rukopisima - dve malo poznate vesti o srpskoj kulturi u XIV veku". Zbornik radova Vizantoloskog instituta, nr 41 (2004): 353–60. http://dx.doi.org/10.2298/zrvi0441353s.
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(nemacki) Der Beitrag umfa?t zwei ganz unterschiedliche Beispiele der F?rsorge um Erwerb und Erhalt von Handschriften. Bald nach 1360 gr?ndete Despot Thomas Preljubovic in Vodena (Edessa) in Nordgriechenland ein Kloster der Theotokos Gabaliotissa, das er neben anderen Sch?tzen mit 37 liturgischen B?chern ausstattete. Bemerkenswert ist dabei die Tatsache, da? sich diese Schenkung zu verschiedenen Zeitpunkten vollzog und sich wohl der wachsenden Anzahl der M?nche anpa?te. Aus einer zweiten, sprachlich nicht immer klaren Notiz geht hervor, wie durch das tatkr?ftige Eingreifen eines Albaners und eines griechischen Hieromonachos ein wertvoller Bestand von 27 B?chern, darunter der heute noch erhaltene codex argenteus von Berat vor einem serbischen Angriff (1357) in Sicherheit gebracht wurde. .
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Schuerch, Christian, Graham L. Barlow, Salil S. Bhate, Nikolay Samusik, Garry P. Nolan i Yury Goltsev. "Dynamics of the Bone Marrow Microenvironment during Leukemic Progression Revealed By Codex Hyper-Parameter Tissue Imaging". Blood 132, Supplement 1 (29.11.2018): 935. http://dx.doi.org/10.1182/blood-2018-99-111708.
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Abstract Introduction The bone marrow (BM) microenvironment consists of various cell types such as mesenchymal stromal cells, endothelial cells, osteoblastic cells and multiple immune cell types including mature myeloid cells and lymphocytes. Recent studies have shown that leukemias can create and maintain a leukemia-supporting BM microenvironment, and vice versa, a dysfunctional BM microenvironment can contribute to leukemia development and progression. Moreover, in tumors the microenvironment is often immunosuppressive and restrains effective anti-tumoral immune responses by adaptive and innate immunity. A better understanding of the precise localization of microenvironmental and immune cell types in intact tissue, and how they physically interact with each other and with tumor cells, will improve our understanding of the mechanisms by which cancer reprograms its microenvironment and may form the basis for novel immunotherapies. Methods CO-Detection by antibody indEXing (CODEX) is a multiplex fluorescence microscopy platform based on DNA-conjugated antibodies that allows the analysis of 50+ markers in a single tissue section. After staining with an antibody cocktail, tissues are imaged in a multi-cycle reaction using a microfluidics system and a fluorescence microscope with a computer automated X/Y/Z stage. DNA-conjugated antibodies are rendered visible using complementary fluorescent DNA probes, followed by imaging, probe stripping, washing and re-rendering. This process is repeated until all the antibodies present in the initial cocktail have been rendered and imaged. Here, we used CODEX to analyze intact BM at the single-cell level (~200nm resolution) during leukemic progression. Chronic myeloid leukemia (CML)-like disease was induced in non-irradiated mice using BCR-ABL1-GFP retrovirus. Tissue sections of femoral bones harvested at different time points after leukemia onset were stained using a 50+ marker CODEX antibody panel to simultaneously identify hematopoietic and leukemic stem and progenitor cells, multiple BM microenvironmental cell types, myeloid and lymphoid cells as well as functional markers. Results We have built an integrated computational pipeline for the analysis of high-dimensional CODEX data that enables the identification and characterization of BM cell types as well as their spatial organization in situ. Raw images were concatenated and aligned using Hoechst nuclear stain as a reference, followed by deconvolution, segmentation, marker expression quantification and spatial compensation. Exported data were clustered in an unsupervised manner using VorteX algorithm, which identified 28 distinct cellular clusters based on marker expression values. All major BM compartments including stromal (vascular, pericytes, osteoblastic), lymphoid (T and B cell subsets), myeloid (megakaryocytes, macrophages, dendritic cells, granulocytes) and progenitor cell types, as well as leukemic cells, were represented. During leukemic progression, the BM microenvironment was dramatically rearranged. Besides the expected growth of the leukemic clone, we observed a massive increase in vascular and osteoblastic cell types, whereas immune cell clusters were significantly reduced. Interestingly, CD71, the transferrin receptor, was strongly up-regulated on tumor cells in advanced leukemia, indicating towards a role for iron metabolism in malignant progression. Furthermore, hierarchical clustering of tissue regions based on cellular composition using X/Y/Z positional information pointed towards the emergence of specific cell-cell interaction modules that developed during leukemic progression, including mutual attraction between B cells and central arterioles. Conclusions High-dimensional imaging of the BM microenvironment by CODEX allows studying the abundance and distribution of cellular elements that are often underestimated or missed by traditional flow cytometry, such as stromal cells, vasculature and megakaryocytes. Importantly, CODEX identifies single cells in their tissue context during leukemic progression and facilitates the discovery of novel cell-cell interactions and cell types as well as unexpected marker constellations. Disclosures Samusik: Akoya Biosciences: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Nolan:Akoya Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Goltsev:Akoya Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.
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Longworth, Aaron J., Sharmila Mallya, Tatyana Lev, Maren Pein, Isam Adam, Antony Lincy, Pascal Naef i in. "Multiomic and spatial immunophenotyping reveals a prominent Runx3 +resident T cell population in the healthy human breast." Journal of Immunology 210, nr 1_Supplement (1.05.2023): 63.12. http://dx.doi.org/10.4049/jimmunol.210.supp.63.12.
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Abstract The role of Runt-domain related transcription factor 3 (Runx3) in the early development of T cells is well established, however recent work has implicated Runx3 as a driver of residency in barrier tissues such as the lung and intestinal epithelium, as well as in the tumor infiltrating lymphocytes of murine and human melanomas. We have identified a subpopulation of resident T cells in the healthy human breast exhibiting constitutive expression of Runx3. Employing single-cell RNA sequencing paired with concurrent sequencing of T cell receptors (TCRseq, 10× Genomics) and oligo-tagged antibodies (Totalseq, BioLegend) specific to canonical markers of memory and effector T cells, we compared the clonality and transcriptome of T lymphocytes isolated from reduction mammoplasty or tumor-patient-derived contralateral mastectomies to those obtained from matched patient peripheral blood. We subsequently utilized highly-multiplexed spatial immunophenotyping through Co-detection by indexing (CODEX, Akoya Biosciences) to infer the role of Runx3 +resident T cells in the healthy human breast based on informatic analysis of the associated cellular neighborhoods. Our analysis finds an abundant population of highly clonal CD8 +Runx3 +cytotoxic T lymphocytes consistently located in the milk-producing lobular and secretory ductal regions of the healthy adult breast, postulating roles in barrier immunity and tissue reconstruction. Furthermore, marked presence of these cells in the contralateral mastectomies of tumor-bearing patients suggests a protective antitumoral role in nonaffected or cleared tissue. Supported by NIH grant R01 (5R01CACA237376-03), T32 (T32-NS121727-01)
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Longworth, Aaron J., Katrina Evans i Devon Lawson. "In situ analysis of the metastatic immune milieu in breast cancer brain metastasis at the single-cell level." Journal of Immunology 208, nr 1_Supplement (1.05.2022): 179.01. http://dx.doi.org/10.4049/jimmunol.208.supp.179.01.
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Abstract Despite advances in early detection and treatment, breast cancer remains the second-leading cause of death among women. Among these cases, incidence of breast cancer brain metastasis (BCBM) carries a poor prognosis with a mean survival of 6 months following diagnosis, demonstrating a drastic unmet need for effective treatments. As the most abundant resident immune cell in the brain, microglia are poised to be effective first-responders to combat tumor infiltration, yet their response to metastases has not been fully characterized. Prevailing literature suggests that microglia promote metastatic outgrowth, however these works fail to adequately discriminate microglia from other brain resident and infiltrating macrophages. Employing a mouse model harboring a deletion in a super-enhancer of macrophage colony-stimulating factor 1 receptor which results in a near-complete loss of microglia, we find more tumor outgrowth compared to animals with microglia. We subsequently compared the metastatic immune milieu in the microglia replete and deficient mice using single-cell RNA sequencing and Akoya’s CODEX (CO-Detection by indEXing) high-parameter immunofluorescence multiplexing platform. We demonstrate that microglia undergo a pro-inflammatory shift in response to BCBM and infiltrating lymphocytes fail to express the inducible costimulatory molecule, ICOS, in the absence of microglia. To understand how microglia promote productive T cell responses to BCBM, we used CODEX to interrogate 20+ different biomarkers in BCBM with or without microglia. Through spatial phenotyping of immune cells from mice with and without microglia we uncover the importance of the microglia/lymphocyte crosstalk in controlling BCBM outgrowth. Supported by NIH Grant (R01 CA237376-02)
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Medrano, Ruan, Fei Han, Bassem Ben Cheikh, Patrick Leinert, Wm Pat Leinert, Oliver Braubach i Robert Schreiber. "309 Visualizing the immunotherapy-induced spatial reorganization of the tumor-immune microenvironment by CODEX multiplex imaging". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (listopad 2021): A334. http://dx.doi.org/10.1136/jitc-2021-sitc2021.309.
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BackgroundTumors contain spatially organized microenvironments in which the location and composition of the cellular components ultimately determine tumor fate. We previously characterized CD45+ cells infiltrating T3 sarcomas using complementary forms of high-dimensional profiling (scRNAseq and CyTOF) and identified key immune cell populations that became associated either with growing tumors in mice treated with control antibody (cmAb) or rejecting tumors in mice treated with immune-checkpoint therapy (ICT) i.e., anti-PD-1 and/or anti-CTLA-4. To better understand the effects of the intratumoral immune cell populations on one another and on the tumor itself, we used CODEX multiplex imaging to simultaneously characterize expression of 35 distinct immune cell markers on tumor tissue sections thereby maintaining the spatial relationships between effector cells and their cognate tumor cell targetsMethodsT3 tumor bearing syngeneic mice were treated with cmAb or a-PD-1/a-CTLA-4 on days 6,9 and 12, harvested on different days, fresh frozen, cut in 8µM sections, transferred to coverslips, and stained with a panel of commercially available and custom-made CODEX antibodies following optimized staining conditions using the manufacturer’s protocol. Whole tumor tissue raw TIFF images were subjected to an image processing pipeline developed by Akoya Biosciences, Inc, where dapi+ cells used for cell segmentation by the Startdist method. Unsupervised clustering using Scanpy toolkit based on normalized marker expression profiles identified and validated 12 unique cell clustersResultsWhen compared to the cmAb group, a-PD-1/a-CTLA-4 tumors harvested on day 10 displayed a marked increase in percentage as well as density of CD4+ and CD8+ T cells, Ly6G neutrophils, MHC-II+cd11c+cd24+DCs and a decrease of CD140a+ tumor cells. Spatial analysis indicated statistically significant differences in the organization of these cell types upon treatment with a-PD-1/a-CTLA-4 compared to cmAb treatment. Specifically, immune cells were found at the border of the tumor in cmAb treated mice and heavily infiltrated tumors following ICT. Neighborhood identification analysis revealed changes in the composition of the main neighborhood clusters, of which the top three clusters present in cmAb treated tumors (macrophage, tumor, and other immune cells) were substituted by clusters of CD4+ and CD8+ T cells, neutrophils, and macrophages.ConclusionsThese results not only confirm the remodeling of both the lymphoid and myeloid compartments previously observed with scRNAseq and CyTOF but also suggest that changes in the spatial organization of immune cells are drivers of the tumor rejection process upon treatment with ICT.
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deLuca, Emilie Patton. ""Livre des simples medecines," Codex Bruxellensis IV 1024: A 15th-century French Herbal. Enid Roberts , William T. Stearn , Carmelia Opsomer". Isis 76, nr 4 (grudzień 1985): 631–32. http://dx.doi.org/10.1086/354016.
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Acquisgrana, María Del Rosario, Laura Cecilia Gómez Pamies i Elisa Inés Benítez. "Hydrothermal Treatment to Remove Tannins in Wholegrains Sorghum, Milled Grains and Flour". Food Science and Nutrition Studies 3, nr 4 (30.10.2019): p122. http://dx.doi.org/10.22158/fsns.v3n4p122.
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Pigmented sorghum with high content of tannins were studied in this work. Tannins bind to proteins and reduce their availability. A hydrothermal treatment was carried out to reduce tannins. A control sample of non-pigmented pericarp variety was used. After the treatment, grains were milled, and a part was separated for wholegrain flour elaboration. Several determinations were done after treatment: tannins (T), total antioxidant capacity (TAC) and total polyphenols (TPP) content. TPP and TAC in wholegrain pigmented sorghum were 3.9 to 12.3 and 2.3 to 3.5 times higher than those of non-pigmented sorghum, respectively. In all sorghum varieties the extractions of TPP decreased with milling. TAC in flour increased 3.3 times the initial value for non-pigmented sorghum, whereas for the other sorghum samples it increased slightly from 1.1 to 1.3 times the initial value. In flours there was a noticeable reduction in T, with respect to the wholegrain. It was possible to conclude that the hydrothermal treatment allowed lower levels of tannins than those established in the Codex for both wholegrain sorghum and flour. This reduction makes it possible to obtain flour which may be suitable for food processing and the recovery of tannins for other uses.
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Kioridis, Ioannis, Maria Sourba i Dimosthenis Stratigopoulos. "The image of the Greeks in the greek (codex H) and aragonese (Arag.) Chronicle of Morea". Studia Philologica Valentina, nr 23 (30.03.2022): 45. http://dx.doi.org/10.7203/sphv.23.21704.
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The study examines the image of the Greeks in two of the codices of the Chronicle of Morea, the H and the Arag ., texts of the 14th century, with the lost prototype tracing back to t he start of the same century. The image of the G reeks (which are usually called Ρωμα?οι and griegos respectively in the two texts )), is directly linked with the identity of the authors a nd the targeting of the texts ? composition The author of H aligns wit h the Franks, he disp arages the Greeks of Constantinople, while exhibiting a more positive attitude about the local Greeks of Morea. He does not hesitate to distort historical reality it self in order to achieve his goals, which are praising the Villehardouins and the nostalgic reminiscing of an era that had been lost for good. On the other hand, on the Aragonese text, the author’ s stance on the Greeks and the Franks is generally negative. He, same as before, is positive regarding the local Greeks of Morea . The author never align s himself with the Francs, which makes him more objective. He is mainly interested in the subjects that relate to the Kingdom of Aragon, while his stance is influenced by the fact that his work is completed not long after the described events, comissioned by an prominent ex administrator of Morea.
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Monkman, James, Afshin Moradi, Connor O'Leary, Zhenqin Wu, Steven Hamel, David Mason, Fabian Schneider i in. "Abstract 4627: Immune profiling of immunotherapy and adjuvant chemotherapy pretreatment NSCLC tissues by CODEX". Cancer Research 83, nr 7_Supplement (4.04.2023): 4627. http://dx.doi.org/10.1158/1538-7445.am2023-4627.
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Abstract Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma subtypes, is a leading cause of cancer deaths worldwide. Treatment of NSCLC has advanced from chemotherapy modalities to the use of immunotherapy, namely immune checkpoint inhibitors (ICIs) which enhance the adaptive immune response against tumour cells. Thus, while the immune cell composition of tumours and its influence on treatment outcomes is poorly understood, it likely holds the key to effective, personalized treatment regimens. Here we profiled an adjuvant chemotherapy (n=61) as well as a second line immunotherapy (n=42) NSCLC cohort by the Phenocycler CODEX technology (highplex spatial proteomics) to investigate the association between immune composition and patient outcome. We applied a panel of 38 markers to delineate naïve, memory, cytotoxic and hyperactivated T cell states, as well as B cells, Tregs and myeloid lineage innate immune cell types. Our study sought to understand the heterogeneity of tumour-immune composition across patients and investigate the spatial neighbourhoods and clusters that these cells inhabit within TMA cores. We used Phenoplex™ software for tissue segmentation (into classes for tumor, stroma, artifacts, blood vessels, etc.), cellular segmentation, and cellular phenotyping based on thresholds for each marker, and then performed spatial analyses (distances, interactions, neighborhoods) using SpatialMap1 to identify cellular motifs associated with clinical phenotypes. Our study has identified spatial features associated with immune contexture linked to therapy outcome in both chemotherapy and immunotherapy modalities. Taken together, our study demonstrates the utility of spatial proteomics to identify cellular features associated with outcome to therapy in lung cancer. 1) Trevino A, Ivison G, Hamel S, Chiou A (2022). SpatialMap: Analysis of Spatial Biology Data. R package version 0.4.57. Citation Format: James Monkman, Afshin Moradi, Connor O'Leary, Zhenqin Wu, Steven Hamel, David Mason, Fabian Schneider, James Robert Mansfield, Aaron Meyer, Ken O'Byrne, Arutha Kulasinghe. Immune profiling of immunotherapy and adjuvant chemotherapy pretreatment NSCLC tissues by CODEX. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4627.
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Villasboas, Jose C., Patrizia Mondello, Angelo Fama, Melissa C. Larson, Andrew L. Feldman, Zhi-Zhang Yang, Ilia Galkin i in. "High Dimensional Tissue-Based Spatial Analysis of the Tumor Microenvironment of Follicular Lymphoma Reveals Unique Immune Niches inside Malignant Follicles". Blood 136, Supplement 1 (5.11.2020): 17–18. http://dx.doi.org/10.1182/blood-2020-134941.
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Background The importance of the immune system in modulating the trajectory of lymphoma outcomes has been increasingly recognized. We recently showed that CD4+ cells are associated with clinical outcomes in a prospective cohort of almost 500 patients with follicular lymphoma (FL). Specifically, we showed that the absence of CD4+ cells inside follicles was independently associated with increased risk of early clinical failure. These data suggest that the composition, as well as the spatial distribution of immune cells within the tumor microenvironment (TME), play an important role in FL. To further define the architecture of the TME in FL we analyzed a FL tumor section using the Co-Detection by Indexing (CODEX) multiplex immunofluorescence system. Methods An 8-micron section from a formalin-fixed paraffin-embedded block containing a lymph node specimen from a patient with FL was stained with a cocktail of 15 CODEX antibodies. Five regions of interest (ROIs) were imaged using a 20X air objective. Images underwent single-cell segmentation using a Unet neural network, trained on manually segmented cells (Fig 1A). Cell type assignment was done after scaling marker expression and clustering using Phenograph. Each ROI was manually masked to indicate areas inside follicles (IF) and outside follicles (OF). Relative and absolute frequencies of cell types were calculated for each region. Cellular contacts were measured as number and types of cell-cell contacts within two cellular diameters. To identify proximity communities, we clustered cells based on number and type of neighboring masks using Phenograph. The number of cell types and cellular communities were calculated inside and outside follicles after adjustment for total IF and OF areas. The significance of cell contact was measured using a random permutation test. Results We identified 13 unique cell subsets (11 immune, 1 endothelial, 1 unclassified) in the TME of our FL section (Fig. 1A). The unique phenotype of each subset was confirmed using a dimensionality reduction tool (t-SNE). The global composition of the TME varied minimally across ROIs and consisted primarily of B cells, T cells, and macrophages subsets - in decreasing order of frequency. Higher spatial heterogeneity across ROIs was observed in the frequency of T cell subsets in comparison to B cells subsets. Inspecting the spatial distribution of T cell subsets (Fig. 1B), we observed that cytotoxic T cells were primarily located in OF areas, whereas CD4+ T cells were found in both IF and OF areas. Notably, the majority of CD4+ T cells inside the follicles expressed CD45RO (memory phenotype), while most of the CD4+ T cells outside the follicles did not. Statistical analysis of the spatial distribution of CD4+ memory T cell subsets confirmed a significant increase in their frequency inside follicles compared to outside (20.4% vs 11.2%, p < 0.001; Fig. 1D). Cell-cell contact analysis (Fig 1C) showed increased homotypic contact for all cell types. We also found a higher frequency of heterotypic contact between Ki-67+CD4+ memory T cells and Ki-67+ B cells. Pairwise analysis showed these findings were statistically significant, indicating these cells are organized in niches rather than randomly distributed across image. Analysis of cellular communities (Fig. 1C) identified 13 niches, named according to the most frequent type of cell-cell contact. All CD4+ memory T cell subsets were found to belong to the same neighborhood (CD4 Memory community). Analysis of the spatial distribution of this community confirmed that these niches were more frequently located inside follicles rather than outside (26.3±4% vs 0.004%, p < 0.001, Fig. 1D). Conclusions Analysis of the TME using CODEX provides insights on the complex composition and unique architecture of this FL case. Cells were organized in a pattern characterized by (1) high degree of homotypic contact and (2) increased heterotypic interaction between activated B cells and activated CD4+ memory T cells. Spatial analysis of both individual cell subsets and cellular neighborhoods demonstrate a statistically significant increase in CD4+ memory T cells inside malignant follicles. This emerging knowledge about the specific immune-architecture of FL adds mechanistic details to our initial observation around the prognostic value of the TME in this disease. These data support future studies using modulation of the TME as a therapeutic target in FL. Figure 1 Disclosures Galkin: BostonGene: Current Employment, Patents & Royalties. Svekolkin:BostonGene: Current Employment, Current equity holder in private company, Patents & Royalties. Postovalova:BostonGene: Current Employment, Current equity holder in private company. Bagaev:BostonGene: Current Employment, Current equity holder in private company, Patents & Royalties. Ovcharov:BostonGene: Current Employment, Current equity holder in private company, Patents & Royalties. Varlamova:BostonGene: Current Employment, Current equity holder in private company, Patents & Royalties. Novak:Celgene/BMS: Research Funding. Witzig:AbbVie: Consultancy; MorphSys: Consultancy; Incyte: Consultancy; Acerta: Research Funding; Karyopharm Therapeutics: Research Funding; Immune Design: Research Funding; Spectrum: Consultancy; Celgene: Consultancy, Research Funding. Nowakowski:Nanostrings: Research Funding; Seattle Genetics: Consultancy; Curis: Consultancy; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Kymera: Consultancy; Denovo: Consultancy; Kite: Consultancy; Celgene/BMS: Consultancy, Research Funding; Roche: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding. Ansell:Trillium: Research Funding; Takeda: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; AI Therapeutics: Research Funding; ADC Therapeutics: Research Funding.
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Shekarian, Tala, Ewelina Bartoszek-Kandler, Carl Zinner, Christian Schuerch i Gregor Hutter. "EXTH-40. MULTIDIMENSIONAL INTERROGATION OF GLIOBLASTOMA MICROENVIRONMENT TREATMENT RESPONSE IN EXPLANT CULTURES". Neuro-Oncology 23, Supplement_6 (2.11.2021): vi172. http://dx.doi.org/10.1093/neuonc/noab196.679.
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Abstract The immune tumor microenvironment (iTME) of glioblastoma (GBM) contains microglial, macrophage, other myeloid cell populations and as adaptive immune cells. Recent therapeutic strategies for GBM aim at targeting iTME components to induce antitumoral immunity. A patient-tailored, ex vivo drug testing and response analysis platform would facilitate personalized therapy planning, provide insights into treatment-induced immune mechanisms in the iTME, and enable the discovery of biomarkers of response and resistance. Here, we generated patient-derived, live 3D GBM bioreactors from different tumor regions to assess iTME treatment responses to microglia modulators and immune checkpoint inhibitors. Intact GBM tissue specimens from the tumor center and periphery were cultured for 7 days in the presence or absence of anti-PD1, anti-CD47 antibodies or their combination. Tissues were analyzed by CODEX highly multiplexed microscopy using an immune-centered 54-marker panel, and changes in cytokine and chemokine levels in culture supernatants were investigated. A computational pipeline for integrative therapy response assessment was implemented. Explant cultures from n=8 IDH wt GBM were subjected to this integrative personalized analysis. Tissue integrity after 3D bioreactor cultures was comparable to tissue taken directly after surgery. FFPE CODEX workflow was feasible with adequate staining quality in bioreactor cultures. 850'000 single cells were segmented and clustered. Cellular composition between tumor center and the peripheral invasion zone differed significantly in immune phenotypes, cytokine profile and response to innate, adaptive or combinatorial local immunotherapies. Multiplexed cytokine analysis revealed IFNγ response signatures in a subset of center samples, whereas the peripheral invasion zone displayed a blunted cytokine response. This cytokine signature corresponded to cellular composition shifts within specific cellular neighborhoods. CD4 and CD8 T cells were invigorated and left their vascular niche. Our study demonstrates that local immunotherapies enable an active antitumoral immune response within the tumor center, and provides a multidimensional personalized framework for immunotherapy response assessment.
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Shang, Olive, Judi Gordon, Nadya Nikulina, Sejal Mistry, Jasmine Singh, Hailing Zong, Jessica Yuan i in. "49 Highly multiplexed detection of critical immune checkpoints and immune cell subtypes in cancerous FFPE tissues using CODEX". Journal for ImmunoTherapy of Cancer 9, Suppl 2 (listopad 2021): A56. http://dx.doi.org/10.1136/jitc-2021-sitc2021.049.
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BackgroundThere is growing consensus that spatial biology is the key to unlocking the underlying mechanisms of cancer immunotherapy and to predicting patient outcomes. Indeed, a recent example using the Akoya Phenoptics technology revealed a unique phenotypic signature of CD8/Foxp3 positive cells embedded within the tumor microenvironment of patients that responded favorably to PD-1 checkpoint inhibition.1 In this case, the combination of both multiparameter and spatial readouts was required to correlate significantly with outcome. As the number of treatment options expands and knowledge regarding cell types that contribute to treatment mechanisms improves, so too do the number of markers required to analyze responses that enable discovery of new signatures.MethodsHere, we present data from the analysis of human FFPE cancer tissues using an expanded CODEX antibody catalog targeting a variety of immune, immune checkpoint and transcription factors. CODEX enables the highly multiplexed detection of more than 40 targets within the same tissue sample, with single cell resolution and without degradation of the sample.ResultsOur expanded target list enables detection of key macrophage populations, T and B cell subtypes, granulocytes, dendritic cells, natural killer cells, stromal, tumor and epithelial cells. Additionally, the activation state of these immune and tumor cell types can be measured through detection of key immune checkpoints, including PD-1 and PD-L1. Through the addition of these critical markers, both cells known to contribute to treatment outcome and new biomarker signatures can be identified.ConclusionsContinued expansion of spatial biology discovery capabilities will be critical to continuing to improve patient outcomes and to develop new treatment options of solid tumors using cancer immunotherapies.ReferenceBerry S, Taube J, et al. Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade. Science. 2021; 372: 6547.
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Castillo, Simon P., Afrooz Jahedi, Pravesh Gupta, Jason T. Huse, Kasthuri Kannan, Yinyin Yuan i Krishna P. Bhat. "Abstract 6171: Evolution of the spatial myeloid-lymphoid engagement in glioblastoma under temozolomide treatment". Cancer Research 84, nr 6_Supplement (22.03.2024): 6171. http://dx.doi.org/10.1158/1538-7445.am2024-6171.
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Abstract The current standard of care for glioblastoma (GBM), encompassing surgery, chemotherapy, and radiation, fails to extend patient survival beyond ~12-15 months. Even advanced immunotherapies, such as checkpoint blockade and chimeric antigen receptor-armored T-cell therapies, are ineffective in GBM due to tissue-specific niche-dependent escape strategies employed by glioma cells. Immune effectiveness, a finely regulated spatial and context-dependent process, underpins such a dismal state of the present therapeutic options. Herein, we applied CO-Detection by indEXing (CODEX), a state-of-the-art multiplex imaging platform, to elucidate the immune cell networks of the tumor microenvironment. By harnessing computational tools on multiplexed regions of interest across whole-slide images, we characterize the immune repertoire of GBMs by studying intratumor heterogeneity across space-histological territories- and time, matching pre- and post-treatment tissue sections of GBMs from seven patients under treatment (Stupp protocol). We aimed to assess changes in the interactions between the two main compartments of the immune system, myeloid and lymphoid, pre- and post-treatment using spatial statistics. We designed a computational workflow for the georeferencing, classification, and phenotyping individual cells of CODEX images across 105 regions of interest, representative of a mosaic of histologically defined cellular tumor (CT) or infiltrating tumor. We defined six major immune phenotypes and evaluated their spatial association with Cd45-Nestin+Olig2+ glioma cells. We modeled the GBM ecosystem and the cells’ spatial coexistence as spatial point processes that allowed the projection of coexistence networks. After stringent quality control, we detected and phenotyped 2.3M cells. Despite interpatient heterogeneity, some patients maintained an even immune composition, while others showed an enrichment in microglia, particularly in CT. Spatial network analyses revealed an increased coexistence between myeloid and lymphoid cells after treatments despite T cells being canonically considered moderately abundant. Quantitatively, the immune meta-network displayed higher edge density and lower modularity post-treatment compared with pre-treatment, reflecting increased lymphoid-myeloid engagement. In summary, we detected an increased spatial myeloid-lymphoid engagement in GBM undergoing chemo-radiation treatments. Spatiotemporal rearrangement of tumor-immune interactions indicates mechanisms implicated in disease recurrence and resistance to standard treatment, opening the frontiers for developing new targeted immunotherapies. Citation Format: Simon P. Castillo, Afrooz Jahedi, Pravesh Gupta, Jason T. Huse, Kasthuri Kannan, Yinyin Yuan, Krishna P. Bhat. Evolution of the spatial myeloid-lymphoid engagement in glioblastoma under temozolomide treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6171.
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Osarumwense, J. O., E. E. Osagiede, F. I. Okolafor i O. N. Aghedo. "ASSESSMENT OF BIOCONCENTRATION FACTOR FOR SELECTED HEAVY METALS IN Talinum triangulare (WATER LEAF) GROWN IN THE VICINITY OF AUTOMOBILE WORKSHOP IN OLUKU, BENIN CITY". Open Journal of Environmental Research (ISSN: 2734-2085) 3, nr 2 (23.12.2022): 54–64. http://dx.doi.org/10.52417/ojer.v3i2.407.
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Sensitive vegetables grown in heavy metals polluted soils tend to accumulate heavy metals which are harmful to the human body even at low concentrations. In this study, the bioconcentration factor (Transfer Factor) was used to assess the accumulation of some heavy metals in Talinum triangulare grown in the vicinity of an automobile workshop in Oluku, Benin City. Physical and chemical parameters found to affect the interactions and mobility of heavy metals in the soil mass were also examined. A pH of 6.17±0.2 was obtained for the topsoil while the middle and bottom soil samples were 5.93±0.4 and 6.00±0.1 respectively, The values of CEC obtained for top, middle, and bottom soil samples were 5.58±0.54, 4.56±0.11, and 3.65±0.14 meq/100g respectively. Soil samples were randomly collected from three depths of 0-10 cm, 10-20 cm, and 20-30 cm with the aid of a soil auger; and T. triangulare were collected within the soil sampling locations. The concentrations of heavy metal were evaluated through the use of atomic absorption spectrophotometer after the samples were subjected to tri-acid digestion techniques. Particle size analysis showed that the soil is a sandy loam texture. High Transfer factor values were ascertained for some metals but none was greater than one. Therefore T. triangulare cannot be considered a hyperaccumulator of heavy metals investigated in this study. However, all metals found in T. triangulare were highly significant (p<0.05), and higher than the permissible limits recommended by FAO/WHO/EC/CODEX. Consumption of T. triangulare harvested from the vicinity of automobile workshops should be highly discouraged to avoid public health hazards.
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Santinon, François, Theodoros Papadopoulos, Meagan-Helen Henderson-Berg, Christophe Gonçalves, Madelyn Abrahams, Natascha Gagnon, Vrinda Gupta, Hsiang Chou, Wilson H. Miller i Sonia Victoria del Rincon. "Identification of p-eIF4E as a new regulator of regulatory T-cell activity". Journal of Immunology 210, nr 1_Supplement (1.05.2023): 70.08. http://dx.doi.org/10.4049/jimmunol.210.supp.70.08.
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Abstract Objective: Phosphorylated Eukaryotic translation initiation factor 4E (p-eIF4E) is a critical regulator of protein synthesis and is phosphorylated by MNK1/2 to promote the translation of a mRNA subset. We have shown that blocking the eIF4E phosphorylation increased the anti-tumor immune response, especially the CD8 T cell activation. However, the role of p-eIF4E in CD4 T cell subsets, and in particular regulatory T cells (Tregs) is still unknown. The aim of this study was to explore the impact that the absence of p-eIF4E could have on the Treg activity as well as in an inflammatory context. Methods: To investigate the role of p-eIF4E on Tregs activity, we used genetically modified mice expressing a non-phosphorylatable form of eIF4E (KI mice). First, we analyzed Treg activity in WT and KI mice and the same mice subjected to dextran sulfate sodium (DSS)-induced colitis. We also analyzed the colonic immune cell infiltration using spectral flow cytometry and CODEX technology. Results: Using our mouse models, we observed that the p-eIF4E lack led to a decrease in Treg stability as well as a decrease in their ability to control the helper T cell (Th) proliferation. In the colitis context, we observed an increase in the disease severity in KI compared to WT mice characterized by an increase in colonic immune infiltration. Moreover, our mesenteric lymph node and colon immunophenotyping revealed a significant decrease in Treg, and an increase in Th expressing IFNγ in KI compared to WT mice. Finally, we observed a decrease in KI Treg ability to migrate to the lymph nodes. Conclusion: These results demonstrate for the first time the preponderant role of p-eIF4E in the control of Treg stability and Treg migration but also in their ability to regulate inflammation.
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Mangaonkar, Abhishek A., Terra L. Lasho, Justin Boysen, Christy M. Finke, Jenna A. Fernandez, Jose C. Villasboas, Christopher Dean i in. "Cellular Interactions within Clonal Dendritic Cell Aggregates Drive Immune Tolerance in Chronic Myelomonocytic Leukemia Bone Marrow Microenvironment". Blood 142, Supplement 1 (28.11.2023): 4077. http://dx.doi.org/10.1182/blood-2023-186856.
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Introduction: Clonal dendritic cell (DC) aggregates in chronic myelomonocytic leukemia (CMML) are seen in approximately 20-30% patients at diagnosis. Previously, these were thought to be comprised of CD123+ plasmacytoid DCs but our data has suggested that these are heterogenous and comprise of myeloid DCs, monocytes, and myeloid-derived suppressor cells. Furthermore, these aggregates uniformly express immune checkpoints such as indoleamine 2,3-dioxygenase-1 (IDO), associate with an IDO-specific systemic impact (increased trytophan catabolism), and expanded regulatory T cell population in CMML, suggesting a role in inducing immune tolerance. DC aggregates are also associated with increased risk of acute myeloid leukemia (AML) transformation and resistance to hypomethylating agents, highlighting that they are important for disease progression in CMML (Mangaonkar A et al. Blood Adv 2020). We performed this study to decipher the architecture of a CMML DC aggregate to understand the complex inter-cellular interactions, and assess their impact on the adaptive immune system. Methods: In this study, we used archival fresh-frozen paraffin-embedded (FFPE) bone marrow biopsy specimens obtained from CMML patients, and isolated monocytes (CD14+ magnetic bead sorting) and lymphocytes (CD14-ve fraction) from untreated CMML and age-matched normal control (NC) peripheral blood mononuclear cells (PBMCs). DCs were cultured from monocytes using a commercial protocol. Spatial architecture of the CMML BM microenvironment was interrogated through multiplex imaging of FFPE samples by co-detection by indexing (CODEX) using 30 markers (CCR6, CD107a, CD11c, CD20, CD21, CD31, CD3e, CD4, CD44, CD45, CD45RO CD56, CD68, CD8, E-Cadherin, FoxP3, HLA-DR, CD14, CD16, CD11b, CD33, CD15, CD66b, CD123, CD303, CD34, CD163 and IDO). Single-cell transcriptomic signatures were analyzed using the 10X single cell Fixed RNA profiling platform, and validated using bulk RNA seq (Illumina stranded mRNA prep) from isolated and cultured cells. Impact of DCs on lymphocytes was assessed via autologous mixed DC-T culture experiments. Results: BM FFPE samples from 5 CMML cases (3 with DC aggregates) were included for multiplex imaging via CODEX. Results confirm the significant interactions of CD8+ and CD4+ T cells with CD123+/HLA-DR+ DCs within a CMML DC aggregate (Fig. 1A). Upon quantitative assessment of cell-cell interactions, IDO+/CD8+T ( P=0.006), IDO+/MDSC ( P=0.005), and IDO+/macrophage ( P=0.001) interactions were significantly increased in CMML samples with versus without DC aggregates . Specific findings were validated using single-stain immunohistochemistry and multiplex immunoflourescence staining. Next, in order to assess transcriptomic signatures within BM at the single-cell level, we chose two cases; CMML (BM aspirate blast% 1, WBC 49.6 x 10 9/L, ASXL1/GATA2/SETBP1/SRSF2 mutations) and AML transformed from CMML (BM aspirate blast% 81, WBC 152 x 10 9/L, NPM1/DNMT3A/TET2 mutations). Approximately, 10,000 cells were obtained and analyzed with cell type annotation through human PBMC reference (Azimuth). Results show an expanded regulatory T cell population in AML compared to CMML (UMAP plot, Fig. 1B), suggestive of immune tolerance. In order to validate findings and perform functional experiments, we used sorted monocytes and cutured DCs from CMML and NC. DC phenotype was confirmed both through visual inspection and flow cytometry, and clonality was confirmed through Sanger sequencing (for previously identified mutations). Differential gene expression analysis through bulk RNAseq showed significant differences between CMML and NC lymphocytes with immunoinhibitory receptor, LILRB2 (log2fold change=7.05, adjusted P=0.0002) being one of the top five significantly upregulated genes, further confirming immune tolerance. Finally, mixed autologous DC-lymphocyte reaction (1:4 ratio) experiments demonstrated that DCs induce T cell tolerance in CMML (expansion of exhausted PD1/TIM3/LAG3+ CD8 T cells) when compared to NC. Conclusion: Clonal dendritic cell aggregates within the CMML bone marrow microenviroment interact with T cells and induce immune tolerance. This represents a novel mechanism of disease progression in CMML with potential therapeutic targets (IDO, LILRB2, and/or CD123).
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Tomelleri, Vittorio Springfield. "Der heilige Wenzel in der (alt)kirchenslavischen Hymnographie". Slovo, nr 73 (19.05.2023): 115–43. http://dx.doi.org/10.31745/s.73.7.
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Im vorliegenden Beitrag geht es um das Offizium (akolouthia) für den heiligen Märtyrer Wenzel, Fürst von Böhmen von 921 bis zu seiner Ermordung durch den jüngeren Bruder Boleslav (929 oder 935). Nach einer kurzen Darstellung des Textes, der von drei Handschriften ostslavischer (Novgoroder) Herkunft aus dem späten 11. bis 12. Jahrhundert überliefert ist, werden Abweichungen sowohl auf makro- (Textstruktur) als auch auf mikrotextueller Ebene (Lesarten) behandelt, mit besonderem Augenmerk auf Binde- und Trennfehler. Die Analyse der Varianten und deren Verteilung zeigt deutlich, dass die drei Textzeugen unabhängig voneinander auf eine gemeinsame Quelle, das nicht erhaltene (westslavische?) Original bzw. den ostslavischen Archetyp zurückgehen und demzufolge ein drei- oder eher zweiästiges Stemma bilden, wobei der älteste Codex T den zwei späteren, Sin und Sof, gegenübersteht. In vielen Fällen, wenn T mit Sin oder Sof übereinstimmt, kann das Original (oder zumindest der ostslavische Archetyp) mit einer gewissen Wahrscheinlichkeit erschlossen werden. Da das Offizium auf einige Episoden aus Wenzels Leben Bezug nimmt, die seinen Tod (28. September) und die Überführung seiner Reliquien nach Prag (4. März) betreffen, kann nicht ausgeschlossen werden, dass es das Ergebnis einer Zusammenstellung verschiedener hymnographischer Quellen darstellt. Das hier gesammelte Material stellt unter Beweis die Relevanz einer kritischen Herangehensweise an die gesamte Texttradition des Wenzeloffiziums, die auch andere Werke aus seinem Zyklus berücksichtigen sollte. Dies wurde uns nämlich ermöglichen, Variationsfälle sowohl in philologischer als auch in linguistischer Perspektive zu untersuchen und zu entwirren.
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Er Demirhan, Buket, i Burak Demirhan. "The Investigation of Mycotoxins and Enterobacteriaceae of Cereal-Based Baby Foods Marketed in Turkey". Foods 10, nr 12 (7.12.2021): 3040. http://dx.doi.org/10.3390/foods10123040.
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In this study, a total of 85 cereal-based baby foods with or without milk (four different brands; A, B, C, and D) collected from Ankara local markets, Turkey were analyzed for mycotoxins, total aerobic mesophilic bacteria (TAMB), and Enterobacteriaceae contamination. Baby foods were analyzed for 12 toxicological important mycotoxins such as aflatoxin B1, B2, G1, and G2; fumonisin B1 and B2; ochratoxin A; sterigmatocystin (STE); deoxynivalenol (DON); zearalenone (ZON); and T-2 toxin and HT-2 toxin by LC-MS/MS multi-mycotoxin method. In addition to these mycotoxins, the presence of aflatoxin M1 (AFM1) was investigated in baby foods containing milk. The classical culture method was used for microbiological analysis. Consequently, at least one mycotoxin was detected in 69.41% of the total samples. The most frequently detected mycotoxins were STE (34.12%) and HT-2 (34.12%). However, AFM1 was not detected in any of the baby foods containing milk. Also, TAMB and Enterobacteriaceae were isolated from 30.59% and 10.59% of samples, respectively. As a result, it was determined that the mycotoxin levels in the analyzed samples were in accordance with the mycotoxin levels specified in the Turkish Food Codex.
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Grant, Robert M. "The Birth of the Codex. By C. H. Roberts and T. C. Skeat. New York: Oxford University Press, 1983. ix + 78 pp. + 6 plates. $32.50." Church History 54, nr 3 (wrzesień 1985): 438–39. http://dx.doi.org/10.2307/3165726.
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Álvarez Aspiazu, Andry, Jaime Vera Chang, Christian Vallejo Torres i Diego Tuarez García. "OBTENCIÓN DE MANTECA A PARTIR DE ALMENDRAS INFESTADAS CON MONILLA, EN CINCO CLONES EXPERIMENTALES DE T. CACAO". Universidad Ciencia y Tecnología 24, nr 105 (11.10.2020): 43–53. http://dx.doi.org/10.47460/uct.v24i105.380.
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Esta investigación se planteó la extracción de manteca a partir de almendras infestadas al 25% con monilla (Moniliophthora roreri Cif & Par.). Se aplicó un diseño completamente al azar con cinco tratamientos y cuatro repeticiones, para la diferenciación entre medias se empleó el test Tukey y para el análisis sensorial el test de Kruscal Wallis. Respecto a los resultados, en el rendimiento de manteca extraída en pasta (g/kg), no existieron diferencias. En cuanto a variables físico-químicas el mejor tratamiento fue T3(CCAT-46-88) con 81,88% de grasa, 1.03% en proteína, 807,80 Kcal/100g de energía y 0,22% de índice de acidez. En el contenido de humedad destacó el testigo (EET-103) con 0.07%. Por otro lado, T4 (CCAT-49-98) presentó el mejor registro de materia seca (99,83%) y carbohidratos (9,52%). Mientras que en contenido de ceniza no existieron diferencias. Finalmente, el análisis sensorial demostró que T1 (CCAT-46-57) obtuvo el mejor perfil sensorial.
Palabras Clave: análisis sensorial, análisis físico-químicos, cacao, rendimiento.
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[20]R. Cuamba, «Caracterización de grasas alternativas de la manteca de cacao,» México D.F., 2008.
[21]C. Arriaga, «Contenido de Ácidos Grasos de la manteca provinientes de mezclas, en distintas fracciones,de semillas de Theobroma cacao y Theibroma bicolor y su uso en la manufactura de chocolate.,» Guatemala, 2007.
[22]S. Lannes, M. Medeiros y L. Gioielli, «Physical interactions between cupuassu and cocoa fats,» Grasas y Aceites, vol. 62, nº 4, pp. 467-478, 2011.
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Šarkić, Srđan. "The Influence of Byzantine Law on Serbian Medieval Law". Slovene 4, nr 2 (2015): 106–18. http://dx.doi.org/10.31168/2305-6754.2015.4.2.5.
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Serbian law from the early 13th century developed under the direct influence of Byzantine law. Serbian jurists adopted Byzantine law through translations of Byzantine legal compilations. The first such translation was the Nomokanon of St. Sabba of 1219. St. Sabba’s Nomokanon contained ecclesiastical rules together with the canonist’s glosses, a translation of part of Justinian’s Novels, and the whole of the Procheiron of Basil I. Between 1349 and 1354, Serbian lawyers created a special Codex Tripartitus, codifying both Serbian and Byzantine law. The Russian scholar T. Florinsky noticed this as long ago as 1888, pointing out that in the oldest manuscripts, Dušan’s Code is always accompanied by two other compilations of Byzantine law: the abbreviated Syntagma of Matthew Blastares and the so-called Code of Justinian. In addition to translations of Byzantine legal miscellanies, Serbian lawyers also adopted a great number of the institutions of Roman law. However, Serbian jurists were not educated in Bologna so, as a consequence, Roman law was adopted in an indirect way, i.e., through Greek (Byzantine) translations and not from original Latin texts. Dušan’s Code, as the most important legal source of medieval Serbian law, took about sixty articles directly from the Basilica: the most important are articles 171 and 172.
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Segura, Verónica, Miguel Ángel Siglez, Ángela Ruiz-Carnicer, Izaskun Martín-Cabrejas, María van der Hofstadt, Encarnación Mellado, Isabel Comino i Carolina Sousa. "A Highly Sensitive Method for the Detection of Hydrolyzed Gluten in Beer Samples Using LFIA". Foods 12, nr 1 (28.12.2022): 160. http://dx.doi.org/10.3390/foods12010160.
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Most gluten analysis methods have been developed to detect intact gluten, but they have shown limitations in certain foods and beverages in which gluten proteins are hydrolyzed. Methods based on G12/A1 moAbs detect the sequences of gluten immunogenic peptides (GIP), which are the main contributors to the immune response of celiac disease (CD). Immunogenic sequences with tandem epitopes for G12/A1 have been found in beers with <20 mg/kg gluten, which could be consumed by CD patients according to the Codex Alimentarius. Therefore, an accurate method for the estimation of the immunogenicity of a beer is to use two moAbs that can recognize celiac T cell epitopes comprising most of the immunogenic response. Here, a specific and sensitive method based on G12/A1 LFIA was developed to detect GIP in beers labeled gluten-free or with low gluten content, with an LOD of 0.5 mg/kg. A total of 107 beers were analyzed, of those 6.5% showed levels higher than 20 mg/kg gluten and 29% showed levels above the LOD. In addition, G12/A1 LFIA detected gluten in 15 more beer samples than competitive ELISA with another antibody. Despite their labeling, these beers contained GIP which may cause symptoms and/or intestinal damage in CD patients.
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Bautista Vega, Anderson, i Segundo Víctor Olivares Muñoz. "Dilución y concentración de Theobroma cacao L en las características del néctar de Passiflora edulis". Revista Científica UNTRM: Ciencias Naturales e Ingeniería 5, nr 1 (10.11.2022): 24. http://dx.doi.org/10.25127/ucni.v5i1.885.
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<p><strong> </strong></p><p><strong> </strong></p><p>El objetivo de investigación fue determinar el efecto de la dilución y concentración de mucilago de cacao (<em>T. cacao </em>L) en las características fisicoquímicas y sensoriales de néctar de maracuyá (<em>P. edulis</em>), para ello se utilizó un diseño completamente al azar (DCA) con un arreglo factorial (3A*3B) donde el factor A: porcentaje de mucílago (A1: 5%, A2: 10%, A3: 15%) y factor B: dilución (B1: 1:3 ; B2: 1:5; B3: 1:7). Se modularon las características fisicoquímicas y sensoriales; mediante análisis de varianza, prueba de Tuckey y Prueba de Friedman al 95% de confianza, se determinó que a una dilución de 1:5 y adición de 15% de mucílago se obtiene las mejores características que confluyen en la denominación de néctar según el Codex Alimentarius STAN (247-2005); con calificación sensorial promedio de me gusta (4); asimismo registró pH 3,61; densidad 1061 kg/m3; sólidos totales 14,2 ° Brix; acidez titulable 0,47 % de ácido cítrico; viscosidad 8,87 cp; humedad 85,63%; ceniza 0,29%, grasa 0,03% y proteína (Factor 6,25) 0,43%.</p>
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Ekambaram, Gnanadesigan. "Impact of smart phone use on adolescence health in India". Bioinformation 19, nr 11 (30.11.2023): 1090–93. http://dx.doi.org/10.6026/973206300191090.
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Smart phone use is on the rise globally, which may have an impact on people's health. The second-largest country in terms of mobile phone usage is India. However, there aren't many studies that have been done in India to evaluate its health impacts. Therefore, it is of interest to assess the effectiveness of codex on the impact of smart phone use on various dimensions of health status among adolescence. The pre-test mean score for knowledge regarding the impact of smart phones on physical health was 1.92, while the post-test mean score was 3.75. The pre-test and post-test standard deviations were 0.91 and 0.93, respectively, and the mean deviation score was the ‘t’-value that was 11.000 and Significant at the p<0.001*** level. The research was conducted in higher secondary school, and 60 students participated. The research design was a pre-experimental design; a self-administered questionnaire was used to assess the knowledge of Students on the Impact of mobile phone use on various dimensions of health. Most people, on average, spend 3 hours and 15 minutes on their phones each day. As adolescents are engaged in smart phone use, it disturbs their sleep patterns, adversely impacting their short-term memory .
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Barbara, Maria Cristina Santa, Lígia Luriko Miyamaru i Jaim Lichitig. "Determinação de basicidade em produtos alisantes de cabelos contendo guanidina e hidróxido de cálcio em sua formulação". Revista do Instituto Adolfo Lutz 66, nr 2 (1.04.2007): 176–80. http://dx.doi.org/10.53393/rial.2007.66.32829.
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O presente trabalho teve como objetivo determinar a basicidade em cremes alisantes para atender a legislação vigente que permite no máximo 7,0% p/p expresso em hidróxido de cálcio. Este estudo realizou a comparação entre dois métodos duas técnicas analíticas titulométricas. Foram utilizadas amostras “brancas” (sem princípio ativo) enriquecidas com hidróxido de cálcio nas concentrações de 3,0%, 6,0% e 8,0% (p/p); sendo oito replicatas para cada concentração. A determinação de basicidade foi efetuada por titulação direta de íons cálcio na amostra, pesou-se a amostra equivalente a 0,1500 g de hidróxido de cálcio, diluiu-se em água e ácido clorídrico, sob agitação e aquecimento, resfriou-se e titulou-se com EDTA 0,0500 mol/L, utilizando azul de hidroxinaftol como indicador. A titulação direta por neutralização de íons OH- com HCl e fenolftaleína mostrou que a recuperação não foi satisfatória o que atribuímosa os íons OH- estarem adsorvidos na mistura do creme. A precisão do método foi de 0,03 a 1,3% no intervalo de 2,9-8,0 % Ca (OH)2 (p/p). A recuperação foi obtida no intervalo de 96,0-100,5%. O método do Food Chemicals Codex 4ª edição foi utilizado em comparação ao método adaptado no laboratório. Os testes t e F mostraram que os dois métodos são equivalentes.
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Mari, Tommaso. "A NEW MANUSCRIPT OF CONSENTIUS’ DE BARBARISMIS ET METAPLASMIS". Classical Quarterly 66, nr 1 (2.03.2016): 370–75. http://dx.doi.org/10.1017/s0009838816000021.
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Modern knowledge of the grammarian Consentius’ De barbarismis et metaplasmis, a work valuable for the study of the Latin language, dates back to a relatively recent past: it was only in 1817 that its editio princeps was published by Ph.C. Buttmann, just a few years after the legal scholar A.W. Cramer came across a mention of the then unknown treatise in a ninth-century MS in the Bayerische Staatsbibliothek of Munich, numbered Clm 14666. Based on this solitary manuscript, H. Keil published the short treatise in the fifth volume of his Grammatici Latini. With no little enthusiasm did W.M. Lindsay announce his unearthing of what, in his own words, had ‘long been a “desideratum”, a second authority’ for this text, in the MS F 15 III d at the Universitätsbibliothek Basel; this was followed by E.O. Winstedt's complete collation and M. Niedermann's critical edition. After about a century now there comes to light a third authority, surprisingly enough in a codex which has enjoyed such fame in the past decades that one might wonder how Consentius could have gone unnoticed in it for so long: this is the eleventh-century MS of Venice, Biblioteca Nazionale Marciana Lat. Z. 497 (= 1811), in which the De barbarismis et metaplasmis is contained on fols. 84vb 39 - 90va 39; moreover, a so-far-unnoticed quotation from it (32.9-14), together with one from Consentius’ De nomine et uerbo (Consent. gramm. V 353.6-7), is found on fol. 41vb 16–21 of the same manuscript in a famous grammatical florilegium. The codex, written in Romanesque minuscule and probably originating in Rome, is regarded as a handbook of liberal arts designed by Lawrence Archbishop of Amalfi, formerly a monk at Montecassino, thereafter a teacher in Florence and Rome, where he died in about 1049. Based on palaeographical evidence, F.L. Newton rightfully assumed as an exemplar for this codex a MS in Beneventan script, as some features can be detected that betray the scribal imitation of that typical South Italian script, namely the use of the distinctive abbreviation for eius as ‘ei in ligature with stroke through the descender of the i’, the Beneventan ti ligature for the assibilated sound, and the 2-shaped Beneventan interrogation sign, to which I would add the typical abbreviation for in as a long i cut by a horizontal stroke and the confusion of a and t. Interestingly enough, none of these features is found on fols. 66–95, those containing the new Consentius: from a codicological point of view, this is an autonomous section, written by a different scribe from the rest of the MS and preserving some grammatical texts generally attributed to insular authors, such as Smaragdus’ Liber in partibus Donati (fols. 66–81vb) and part of the compilation entitled Pauca de barbarismo (fols. 81vb - 84vb), which precedes the De barbarismis et metaplasmis; not surprisingly, the new text of Consentius displays numerous features of the Insular script, such as the symbols for enim, autem, eius, est, nihil and et. On this basis it is most likely that this whole section was never included in the Beneventan exemplar, but was added at the time and place of copying of our MS in order to enrich the grammatical content.
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Bozkus, Cansu Cimen, Mona Saleh, Rachel Brody, Stephanie V. Blank i Nina Bhardwaj. "Abstract 253: Analyses of tumor-specific T cell dynamics and tumor immune contexture in microsatellite instability-high cancers in response to first-line therapy". Cancer Research 82, nr 12_Supplement (15.06.2022): 253. http://dx.doi.org/10.1158/1538-7445.am2022-253.
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Abstract Microsatellite instability-high (MSI-H) phenotype arises from defective DNA repair mechanisms and is found in many malignancies, including colorectal and endometrial cancers. Due to high neoantigen loads derived from tumor-specific mutations, evidence of tumor-infiltrating T cells and high response rates to checkpoint blockade (30-60%), MSI-H cancers can be leveraged to study the features of neoantigen-induced anti-tumor immunity in response to therapy and disease outcome. Previously we identified a set of recurrent frameshift (fs) mutations in MSI-H cancers that yielded immunogenic polyepitope neoantigens (neoAgs) eliciting CD8+ T cell responses. Here we investigate whether these shared fs-neoAgs engendered spontaneous T cell responses in MSI-H colorectal and endometrial cancer patients. Using peripheral blood mononuclear cells (PBMCs), we evaluated the frequency of the fs-neoAg-specific T cells by ex vivo IFN-γ ELISPOT upon fs-peptide stimulation. Additionally, we isolated naïve and memory T cells from MSI-H patient PBMCs and expanded fs-neoAg-specific T cells within each subset. Fs-neoAg-induced effector cytokine (IFN-γ, TNF-α) production was measured by flow cytometry and was detected only in the memory subset, supporting the hypothesis that shared fs-neoAgs prime CD8+ T cells in vivo to generate clonally-expanded memory T cells in MSI-H patients. To further evaluate the clonal expansion of fs-neoAg-specific T cells in MSI-H cancer patients, we identified fs-neoAg-specific T cell receptors (TCRs). T cell lines enriched for fs-neoAg-specific T cells were generated from patient PBMCs and sequenced for variable β chains of TCRs. These fs-neoAg-specific TCRs were monitored in the blood and tumor tissues, including those from primary and recurrent sites. Finally, to determine the spatial relationships between the infiltrating immune cells and the malignant cells at single cell resolution, we performed multiplexed immunohistochemistry using CODEX technology. A panel of 35 markers was used to evaluate the myeloid (HLA-DR, CD11c, CD14, CD68, CD206) and T (CD4, CD8, Foxp3) cell subsets, the activation (CD107a, CD69, Ki67) and exhaustion (PD-1, TIM3, LAG3) status of T cells, T cell states (TCF-1, TOX, PD-1) and the presence of tertiary lymphoid structures/antigen presenting cell niches (CD19, CD20, HLA-DR) in the tumor microenvironment of primary or recurrent MS-stable and MSI-H tumors from endometrial cancer patients. We also investigated potential immune escape mechanisms in MSI-H tumors, such as the loss of B2M and MHC-I expression. This study will provide insights into the quality and quantity of shared anti-tumor T cells within the periphery and tumor tissues and will help identify the immune correlates of response or resistance to therapy in MSI-H cancer patients. Citation Format: Cansu Cimen Bozkus, Mona Saleh, Rachel Brody, Stephanie V. Blank, Nina Bhardwaj. Analyses of tumor-specific T cell dynamics and tumor immune contexture in microsatellite instability-high cancers in response to first-line therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 253.
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Yilmaz Eker, Funda, Karlo Muratoglu, Muhsin Ozturk, Bayram Cetin i Serkan Kemal Buyukunal. "Determination of Multimycotoxin in Cereal-Based Products Sold in Open-Air Markets". Foods 12, nr 14 (19.07.2023): 2744. http://dx.doi.org/10.3390/foods12142744.
Pełny tekst źródłaStreszczenie:
In this study, a total of 140 cereal-based foods sold in temporary open-air markets were analyzed by LC-MS/MS for aflatoxin B1, B2, G1, G2, ochratoxin (OTA), zearalenone (ZEN), deoxynivalenol (DON), fumonisin B1, fumonisin B2, citrinin (CIT), HT-2, and T-2 toxins. Breakfast cereals (n:27), cornmeal (n:41), extruded maize (n:32), and oatmeal (n:40) purchased from these alternative shopping areas created to meet the food needs of low-income people in the suburbs formed the sample set of the study. These foods, which are sold in areas that are out of legal control and greatly affected by external environmental conditions, are more open to health risks. Mycotoxins, chemicals of a biological origin, are some of the most important of these risks. In terms of public health, it is important to investigate the presence of mycotoxins in foods, which can cause acute and chronic diseases such as immunosuppression, genotoxic, estrogenic, teratogenic effect, cancer, and liver and kidney dysfunctions. Grain-based foods are often contaminated with a large number of mycotoxins, but legal regulations have not been prepared that consider the health risks associated with the co-existence of mycotoxins. Many of the studies have focused on the presence of a single mycotoxin and the risks it poses. As a result, aflatoxin B1 levels in 28.57% of the samples and total aflatoxin (B1 + B2 + G1 + G2) levels in 26.43% of the samples were determined to exceed the limits defined in the “Turkish Food Codex Contaminants Regulation”. Citrinin could not be detected in any of the samples. The rate of mycotoxin occurrences above the limit of detection (LOD) in grain-based food samples ranged from 22.86% to 99.29%. Total aflatoxin (TAF) + Total Fumonisin (FUM) were found in 83.57% of the samples; TAF + FUM + OTA in 82.14%; TAF + FUM + OTA + T-2 in 44.29%; TAF + FUM + OTA + DON + HT-2, TAF + FUM + OTA + DON + T-2, and TAF + FUM + OTA + DON + ZEN in 22.86% of the samples.
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Er Demirhan, Buket, i Burak Demirhan. "Investigation of Twelve Significant Mycotoxin Contamination in Nut-Based Products by the LC–MS/MS Method". Metabolites 12, nr 2 (26.01.2022): 120. http://dx.doi.org/10.3390/metabo12020120.
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In this study, a total of 80 peanut butter, hazelnut butter, and chocolate samples were obtained from local markets in Ankara, Turkey. These foods were analyzed for twelve toxicological important mycotoxins, such as aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), and aflatoxin G2 (AFG2); fumonisin B1 (FB1) and fumonisin B2 (FB2); ochratoxin A (OTA); sterigmatocystin (STE); deoxynivalenol (DON); zearalenone (ZON); T-2 toxin (T2); and HT-2 toxin (HT2) by the LC–MS/MS multi-mycotoxin method. In addition to this analysis, the presence of total aerobic mesophilic bacteria was investigated in the samples. The samples were analyzed microbiologically using standard procedures. Finally, the minimum and maximum levels of AFB1, AFB2, AFG1, FB2, OTA, STE, DON, ZON, T2, and HT2 in the samples were found to be 0.04–27.37 µg/kg, 0.06–6.19 µg/kg, 0.14–0.40 µg/kg, 2.73–2.93 µg/kg, 0.01–37.26 µg/kg, 0.19–2.25 µg/kg, 11.81–42.09 µg/kg, 0.03–7.57 µg/kg, 1.41–2.54 µg/kg, and 6.94–7.43 µg/kg, respectively. AFG2 and FB1 were not detected in any of the samples. The most frequently detected mycotoxins in analyzed samples were OTA (78.75%) and AFB1 (75%). In addition, total aerobic mesophilic bacteria were isolated from 53.75% of samples. Some of the tested food samples contained mycotoxins above the Turkish Food Codex maximum limit.