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Soldatova, Kristina I., Oleg Ivanovich Kit, Roman E. Tolmakh, Liubov Yu Vladimirova, and Denis S. Kutilin. "Cancer-testis gene-expression features in various tumors." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14260-e14260. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14260.
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e14260 Background: Cancer-testis antigens (CTA) can be an effective target for immunotherapy. Immunotherapeutic approaches targeting CTA in breast cancer (BC), endometrial cancer (EC), ovarian cancer (OC), and colon cancer (CRC) are in the incipient stages of development. The purpose of our study was screening of CTA specific for BC, EC, OC and CRC, based on an analysis of transcriptional profiles of CT-genes. Methods: Tumor and intact tissues of the breast, uterus, ovaries and colon were studied in 35, 30, 20 and 60 patients, respectively. RNAs were isolated using the method described by Chomczynski and Sacchi (2006). The REVERTA-L reagent kit was used for the cDNA synthesis. Relative expression of 16 genes ( MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NYESO1, SSX2, SCP1, PRAME1) was determined by Real-Time qPCR (with GAPDH and GUSB as reference genes). Statistical analysis was performed using the Mann-Whitney test. Results: BC patients showed significantly (p < 0.005) increased expression of MAGEA3, MAGEA4 and GAGE3 in tumor tissues compared to normal ones; EC patients - significantly (p < 0.05) increased expression of MAGEA1, MAGEA2, MAGEA4, MAGEB2, GAGE3, NY-ESO1, SCP1 and PRAME1 in tumor tissues compared to normal ones; OC patients - significantly (p < 0.05) increased expression of MAGEB1, MAGEB2, GAGE1, NY-ESO1 and decreased expression of MAGEA3, MAGEA4, GAGE3, GAGE4, XAGE3, SSX2, SCP1 and PRAME1; CRC patients - significantly (p < 0.05) increased expression of SSX2 and PRAME1, together with decreased BAGE expression, in tumors compared to normal tissues. Conclusions: Analysis of the transcriptional activity of CT-genes revealed the most common diagnostic markers and immunotherapeutic targets for every malignancy: in BC - MAGEA3, MAGEA4 and GAGE3, in EC - MAGEA1, MAGEA2, MAGEA4, MAGEB2, GAGE3, NY-ESO1, SYCP1 and PRAME1, in OC - MAGEB1, MAGEB2, GAGE1 and NY-ESO, in CRC - SSX2 and PRAME1.
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Andrade, Valéria C. C., André L. Vettore, Manuella S. S. Almeida, José S. R. Oliveira, Maria de Lourdes L. F. Chauffaille, Mihoko Yamamoto, Adagmar Andriolo, et al. "Prognostic Impact of Cancer Testis Antigens Expression in Advanced Stage Multiple Myeloma Patients." Blood 110, no. 11 (November 16, 2007): 4733. http://dx.doi.org/10.1182/blood.v110.11.4733.4733.
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Abstract Background: Cancer testis antigens have become the most extensively studied antigen group in the field of tumor immunology. Aims: This study aims to analyze global expression of 14 CT (cancer/testis) antigens in MM to identify possible prognostic markers and therapeutic targets. Patients and Methods: The expression of MAGEA1, MAGEA2, MAGEA3/6, MAGEA4, MAGEA10, MAGEA12, BAGE1, MAGEC1/CT7, GAGE family, LAGE-1, PRAME, NY-ESO-1, SPA17 and SSX1 was studied by RT-PCR in: 15 normal tissues, one pool of 10 normal bone marrow samples, three normal tonsils and bone marrow aspirates from six normal donors, three monoclonal gammophaties of undetermined significance (MGUS), five solitary plasmacytomas, 39 MM samples (95% advanced stage) and MM cell line U266. CodeLink Human UniSet I Bioarrays 10,000 genes was used for arrays analyses. Results: SPA17 was positive in all normal tissues and was excluded for further analyses. MAGEC1/CT7 was positive in bone marrow aspirates from one MGUS and in one plasmacytoma. U266 cell line was positive for all CT antigens, except SSX1. The frequencies of CT antigens expression in MM patients were: MAGEC1/CT7 = 30/39 (77%); LAGE-1 = 19/39 (49%); MAGEA3/6 = 16/39 (41%); MAGEA2 = 14/39 (36%); GAGE family = 13/39 (33%); NY-ESO-1 = 13/39 (33%); BAGE-1 = 12/39 (28%); MAGEA1 = 10/39 (26%); PRAME = 9/39 (23%); SSX-1 = 10/39 (26%); MAGEA12 = 8/39 (20.5%); MAGEA4 and MAGEA10 = 0%. Cox’s regression model showed that GAGE family positivity and number of positive CT antigens > 6 were independent prognostic factors when all patients were analyzed. However, MAGEC1/CT7 expression was the only independent prognostic factor when non-transplanted patients where analyzed. Three samples predominantly positive (> 6) and three samples predominantly negative (0 or 1) for the 13 analyzed CT antigens were submitted to microarrays analyses. 147 genes were overexpressed in predominantly positive CT antigens samples. Conclusions: Based on our findings, MAGEC1/CT7, MAGEA3/6 and LAGE-1 seem good candidates for immunotherapy, since together they are overexpressed in 85% of our MM cases. Besides, GAGE family expression, number of CT antigens > 6 and MAGEC1/CT7 seem to have impact on MM prognosis. Also, the results of arrays analyses corroborate the hypothesis that MM can be separate in two groups: predominantly positive and predominantly negative for CT antigens, meaning that these antigens may have important role for MM biology.
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Kutilin, D. S., and Kh A. Mogushkova. "EFFECT OF ANTHRACYCLINE ANTITUMOR ANTIBIOTICS UPON TRANSCRIPTION ACTIVITY OF CANCER-TESTIS ANTIGENS IN MODEL EXPERIMENTS WITH HeLa CELLS." Medical Immunology (Russia) 21, no. 3 (July 13, 2019): 539–46. http://dx.doi.org/10.15789/1563-0625-2019-3-539-546.
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Cancer-testis antigens (CTA) can be used as a target for immunotherapy of various malignant tumors, including cervical cancer. However, immunotherapy is often used in combination with anthracycline chemotherapy, in particular, doxorubicin (DXR). Their effects upon expression of CTA genes have not been yet studied. Therefore, we studied the effects of doxorubicin at different concentrations and exposure time upon transcriptional profile of 17 cancer-testicular (CT) genes of HeLa CCL-2 cells. A long-term line of human cervical cancer cells (HeLa CCL-2 line) was used in this work. Culturing of HeLa CCL-2 cells was carried out in sterile culture flasks with adhesive surface and ventilated lids at 5% CO2, and 95% humidity at 37 °C, in RPMI-1640 medium with 10% fetal bovine serum, supplied with gentamicin (50 μg/ml), and different concentrations of doxorubicin: 0 μg/ml (control), 2 μg/ml, and 4 μg/ml. Expression levels of 16 RT-genes were determined by quantitative RT-PCR using a Bio-Rad CFX96 thermal cycler. Normalization of results was performed against a reference gene, and expression of tested genes in the control samples. We have found that the time of in vitroexposure, and concentration of doxorubicin exert a significant influence upon expression ofMAGEA1, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, BAGE, CTAG1B, XAGE3, NY-ESO1, PRAME1andSYCP1genes, however, without affecting theSSX2, MAGEA2, GAGE4andMAGEC1expression, and DXR concentration as a single factor did not affectMAGEB1andMAGEB2expression. Time of response to DXR effects enabled us to discern early cancer testicular genes with increased expression (MAGEA1, MAGEA3, MAGEA4, NY-ESO1, SYCP1), reduced expression (GAGE1andBAGE), and late inducible testicular genes (GAGE3andXAGE3). These results must be taken into account when carrying out immunotherapy based on the dendritic-cell vaccine technology.
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Riente, Fabrizio, Umberto Garlando, Giovanna Turvani, Marco Vacca, Massimo Ruo Roch, and Mariagrazia Graziano. "MagCAD: Tool for the Design of 3-D Magnetic Circuits." IEEE Journal on Exploratory Solid-State Computational Devices and Circuits 3 (December 2017): 65–73. http://dx.doi.org/10.1109/jxcdc.2017.2756981.
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Zewdu, Eden B., Rachel M. Gonzalez, Yan Ma, Derek Ling, Xiaomin Hu, Qi Ren, Ranran Zhang, et al. "Abstract 2803: A renewable IHC control tool CytoSections࣪ for defining MAGEA3, MAGEA4, and MAGEA9 antibody specificity." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2803. http://dx.doi.org/10.1158/1538-7445.am2022-2803.
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Abstract Melanoma-associated antigen gene A (MAGEA) family proteins are expressed in a variety of tumors with each MAGEA protein having unique roles in cancer pathogenesis. The MAGEA members lack of expression in normal tissue and their role in cancer make them well suited for targeted cancer immunotherapy. Thus, knowing which MAGEA protein expression exists in a tumor is important. However, the MAGEA family shares sequence similarity that makes it difficult to find antibodies that are specific to just one family member. It is also challenging to source tissue generally with HIPAA regulation and even more so to get tissue representation of all 12 MAGEA family members. Here we present CytoSections as an alternative to patient control tissues. CytoSections are formalin fixed, paraffin embedded (FFPE) section of over-expression cell pellets. These cells were transfected with expression plasmids coding for genes of individual MAGES family. In this study, CytoSections are used to screen antibodies to all 12-member MAGEA family of proteins. The MAGEA family members were initially shown positive by targeted protein expression in western and immunohistochemistry using DDK tag antibody. Then multiple MAGEA3, MAGEA4, MAGEA9 antibodies were assessed by IHC to determine their specificity to their intended target. Using MAGEA family as a pilot project, we show that CytoSections is a verified, reproducible, and renewable alternative to human control tissues and serves as an ideal tool for antibody specificity assessment. Citation Format: Eden B. Zewdu, Rachel M. Gonzalez, Yan Ma, Derek Ling, Xiaomin Hu, Qi Ren, Ranran Zhang, Li-Hui Lei, Krishnan Allampallam, Dezhong Yin, Xuan Liu, Wei Fu. A renewable IHC control tool CytoSections࣪ for defining MAGEA3, MAGEA4, and MAGEA9 antibody specificity [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 2803.
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Gerdemann, Ulrike, Anne S. Christin, Conrad Russell Cruz, Carlos A. Ramos, Donald R. Shaffer, Stephen Gottschalk, Helen E. Heslop, et al. "Broad Spectrum Tumor Antigen-Specific Cytotoxic T Lymphocytes (CTL) for Therapy of Hematological Malignancy." Blood 114, no. 22 (November 20, 2009): 4083. http://dx.doi.org/10.1182/blood.v114.22.4083.4083.
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Abstract Abstract 4083 Poster Board III-1018 Tumor immunotherapy using cytotoxic T lymphocytes (CTLs) can effectively treat EBV-associated tumors such as Hodgkin's Lymphoma (HL). To extend the benefit of CTL therapy to other non-viral associated tumors we have now developed a means of generating CTLs that recognize a wide spectrum of non-viral tumor-associated antigens (TAA) expressed on a range of hematological malignancies, including Survivin, MAGEA4, Synovial sarcoma X (SSX2), WT1, Prame, Proteinase 3 (PR3), as well as TAAs such as Alpha-fetoprotein (AFP), MAGEA1 and MAGEA3, which are expressed on solid tumors. The generation of TAA-CTL is complicated by the low frequency of circulating reactive T cells which are often anergized or tolerized. We therefore assessed the potency of different cytokine combinations to overcome T cell anergy. The cytokines tested were Th1 polarizing (IL12, IL18, IL27), pro-survival/-proliferative (IL7, IL15, IL4), and Treg inhibitory (IL-6). We first used autologous dendritic cells (DCs) pulsed with overlapping peptide libraries (pepmixes) spanning the different antigens to stimulate T cells in the presence of the optimal cytokine combination. To further optimize the potency of this approach we chose to use combinations of antigens to produce multi TAA-CTL. The use of pepmixes spanning entire antigens as a stimulus both increases the range of suitable patient HLA polymorphisms beyond those matched to individual peptide epitopes and to reduce the risk of tumor immune evasion that is often observed when single defined-epitope TAA peptides are used as a stimulus. Antigen combinations were chosen based on their tumor expression profile; e.g. to target lymphoma we grouped SSX2, Survivin, and MAGEA4, for leukemia we targeted WT1, Prame, PR3, and Survivin and for hepatocellular carcinoma we combined MAGEA1, MAGEA3 and AFP. Using lymphoma as a model system we were consistently able to generate TAA CTL directed against SSX2, Survivin, and MAGEA4 (n=6 healthy donors). The lines were polyclonal comprising CD4+ (mean 57+/-7%) and CD8+ (mean 40+/-16%) T cells, and showed reactivity against SSX2 (median 345 spot forming units (SFU)/1×106 CTL, range 20-4065), Survivin (median 290 SFU/1×106 CTL, range 30-4632.5) and MAGEA4 (median 255 SFU/1×106 CTL, range 27.5-2962.5), using the relevant pepmixes as a stimulus in ELIspot assays. The CTL were also cytolytic against autologous pepmix-pulsed targets; SSX2 (mean 53+/- 32% specific lysis) and Survivin (30%) at an effector:target (E:T) ratio of 40:1, as well as against whole antigen-expressing targets (30% killing of fibroblasts expressing Survivin from a retrovirus vector, E:T 100:1) with no recognition of non-transduced control targets (9%). For leukemia we generated CTL lines with reactivity against WT1 (mean 733 SFU/1×106 CTL +/-88), Prame (mean 555 SFU/1×106 CTL +/-326), PR3 (mean 145 SFU/1×106 CTL +/-156), and Survivin (mean 32 SFU/1×106 CTL +/-25), n=2. We were similarly successful in generating multi TAA-CTL targeting hepatocellular carcinoma with reactivity for MAGEA1, MAGEA3 and AFP (mean 740+/-969, 929+/-624, 163+/-117 SFU/1×106 CTL, respectively), (n=2). These multi TAA-CTL were generated using pepmixes, which may not be well suited to clinical use. To more accurately target tumors expressing naturally processed antigens, we reproduced these experiments using DCs nucleofected with tumor antigen-encoding DNA plasmids. Using this approach we were consistently able to generate polyclonal SSX2- and MAGEA4-specific T cells. Production of Survivin-reactive cells required a plasmid encoding a Survivin-ubiquitin fusion protein to enhance proteosomal processing, degradation and subsequent presentation. By significantly increasing expression of CD70 on DCs [from median 23.4% (range 13.3-48.8) to median 61.9% (range 46.7-83.8)], (p=0.025) using nucleofection (n=4), we could also enhance the production of in vitro expanded MAGEA3-specific T-cells (from 822 SFU/1×106 CTL to 2460 SFU/1×106 CTL). Finally, we successfully substituted CD40L activated autologous B-blasts for DCs to reduce the volume of patient blood required and to facilitate the logistics of preparation. This study shows the successful generation of tumor specific CTL lines targeting multiple tumor antigens simultaneously to reduce the risk of tumor immune escape and describes a technology feasible for clinical application targeting a broad spectrum of hematologic malignancies. Disclosures: No relevant conflicts of interest to declare.
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Fain, Jean S., Aurélie Van Tongelen, Axelle Loriot, and Charles De Smet. "Epigenetic Coactivation of MAGEA6 and CT-GABRA3 Defines Orientation of a Segmental Duplication in the Human X Chromosome." Cytogenetic and Genome Research 159, no. 1 (2019): 12–18. http://dx.doi.org/10.1159/000502933.
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The human genome harbors many duplicated segments, which sometimes show very high sequence identity. This may complicate assignment during genome assembly. One such example is in Xq28, where the arrangement of 2 recently duplicated segments varies between genome assembly versions. The duplicated segments comprise highly similar genes, including MAGEA3 and MAGEA6, which display specific expression in testicular germline cells, and also become aberrantly activated in a variety of tumors. Recently, a new gene was identified, CT-GABRA3, the transcription of which initiates inside the segmental duplication but extends far outside. According to the latest genome annotation, CT- GABRA3 starts near MAGEA3, with which it shares a bidirectional promoter. In an earlier annotation, however, the duplicated segment was positioned in the opposite orientation, and CT-GABRA3 was instead coupled with MAGEA6. To resolve this discrepancy, and based on the contention that genes connected by a bidirectional promoter are almost always co-expressed, we decided to compare the expression profiles of CT-GABRA3, MAGEA3, and MAGEA6. We found that in tumor tissues and cell lines of different origins, the expression of CT-GABRA3 was better correlated with that of MAGEA6. Moreover, in a cellular model of experimental induction with a DNA demethylation agent, activation CT-GABRA3 was associated with that of MAGEA6, but not with that of MAGEA3. Together these results support a connection between CT-GABRA3 and MAGEA6 and illustrate how promoter-sharing genes can be exploited to resolve genome assembly uncertainties.
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Riente, Fabrizio, Umberto Garlando, Giovanna Turvani, Marco Vacca, Massimo Ruo Roch, and Mariagrazia Graziano. "Corrections to “MagCAD: A Tool for the Design of 3-D Magnetic Circuits” [2017 65-73]." IEEE Journal on Exploratory Solid-State Computational Devices and Circuits 3 (December 2017): 111. http://dx.doi.org/10.1109/jxcdc.2018.2794158.
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Seager, RJ, Erik Van Roey, Shuang Gao, Jonathan Andreas, Vincent Giamo, Blake Burgher, Felicia Lenzo, et al. "64 Cancer testis antigen co-expression landscape in solid tumors." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A69. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0064.
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BackgroundCancer testis antigens (CTAs) are tumor antigens that have a highly tissue-restricted expression but are often expressed in diverse malignancies. With their highly immunogenic expression limited to tumor cells, CTAs have become a prime target for cancer vaccinations and T-cell-based therapy with chimeric T-cell receptors. In this study, we investigated the landscape of 17 CTA (NY-ESO-1, LAGE-1A, and 15 other CTAs) in the context of the tumor immune microenvironment of real-world clinical tumors spanning multiple histologies.MethodsRNA-seq was performed on 5450 FFPE tumors, and the expression of each of the 17 CTAs were classified as Positive (nRPM≥20) or Negative (nRPM<20). Pearson correlation analysis was conducted on the nRPM values for each CTA to determine co-expression relationships between any of the 17 CTAs. In order to visualize patterns in the CTA expression landscape, heatmap analysis was performed, using hierarchical clustering with Pearson’s correlation as a distance measure to reveal patterns in CTA status across all samples and CTAs.Results5450 tumor samples analyzed in this study spanned 39 histologic types of tumor and were predominantly composed of lung cancer (40.4%) followed by colorectal cancer (10.6%) and breast cancer (8.6%). Positive CTA prevalence ranged from 2.4% (GAGE13) to 31.5% (XAGE1B). A high degree of significant correlation between the expression of all CTAs was observed, with only GAGE10, XAGE1B, MLANA, MAGEA4, GAGE13, and SSX2 having a no significant correlation with at least one other CTA. Three key groups of co-expressed CTAs were observed: 1) NY-ESO-1, LAGE-1A, MAGEA12, MAGEA3, MAGEA1, MAGEA10, and MAGEA4 (0.36≤R≤0.82); 2) GAGE12J, GAGE2, GAGE1, GAGE13 (0.58≤R≤0.72); 3) SSX2, BAGE, MAGEC2 (0.4≤R≤0.58). The three remaining CTAs (GAGE10, XAGE1B, and MLANA) had little or no (R<0.22) correlation with any other CTA or each other. Clustering CTAs across all samples revealed three CTA expression clusters: 1) samples that express a collection of multiple CTAs; 2) samples that express mostly XAGE1B, over-represented by lung cancer (p=1.51e-296); 3) samples that express mostly GAGE10, over-represented by neuroendocrine tumors (p=1.64e-05).ConclusionsAcross multiple cancer subtypes, the expression of a CTA occurs in the context of other CTAs, and specific groups of CTAs are likely to co-express, forming expression patterns characteristic to tumor subgroups. These findings provide a scientific base for selecting appropriate CTAs and designing multiplex vaccination in immunotherapies of a variety of tumors. Further studies are needed to understand the relationship of these CTAs with traditional and emerging immune-oncology biomarkers.
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Hurtado López, Ana M., Tzu Hua Chen-Liang, Joaquín Panadero, Eduardo José Salido, Victor Beltrán, Begoña Muiña, Noelia Navarro-Villamor, et al. "TFDP3and DDX53 are Highly Re-Expressed after One Cycle of Azacitidine in Myelodysplastic Syndrome Patients Achieving Complete Response: A Cancer Testis Antigen RNA-Seq Screening." Blood 132, Supplement 1 (November 29, 2018): 4340. http://dx.doi.org/10.1182/blood-2018-99-117851.
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Abstract Background and Aim: Azacitidine have shown clinical activity in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), particularly at low, non-cytotoxic doses favoring hypomethylation over cytotoxicity. Cancer/testis antigens (CTAs, encoding for immunogenic proteins which are normally expressed in the testicles and trophoblastic cells of the ovary, have been shown to undergo derepression after the use of demethylating agents in cancer cell line models. We took advantage of the unique model of Aza-treated high risk MDS to in vivocharacterize candidates for immunotherapy following hypometilating therapy. Methods:Targeted RNA-Seq (tRNA-Seq) designed to capture 214 CTA genes was performed in 19 MDS or CMML patients at day 0 and at day +28 after first AZA cycle. In 10 patients the analysis was extended to third and/or four cycles. Sequencing, coverage, mapping and alignment was performed using the Ion Torrent Browser Suite. We used LIMMA package or empirical analysis of digital gene expression data in R (edgeR) to identify differential expressed genes. A homogeneous treatment schedule with AZA (75 mg/m2/day x 7 days) was received by each patient.The response criteria were from IWG 2006, including a bone marrow and cytogenetic reevaluation after 6 cycles. The main candidates selected from de tRNA-seq experiment were characterized at protein level in cell lysate and/or plasma by Western Blot. Primary antibodies used from Thermo Fisher were: ADAM29, DDX53, PRAME, B-TUBULINA, FAM46D, B-ACT, TMPRSS12, MAGEB4, GAPDH, MAGEA1, MAGEA2, TSPY2, Cxorf48, DNAJB8, NY-ES0-1, CT83/Cxorf61 and TFDP3 from Santa Cruz Biotechnology. We used either cell lysate or plasma to study the protein levels in non-reducing SDS-PAGE at different acrylamide concentration depending on the protein size. ImageJ was used to quantify protein levels. Results:The median age of the cohort was 69 (range 48-81 years). The cohort consisted of 16 MDS and 3 CMML patients. MDS Patients were stratified based on IPSS as low or intermediate-1 (n=14) and intermediate-2 or high (n=2) risk groups and CMML patients based on a CPSS of intermediate-2 (n=3). Five patients were classified as complete responders achieving a complete cytogenetic and/or marrow remission (CR). Regarding the tRNA-Seq, on average, we achieved 3.888.308 mapped reads per sample (p25-p75, 1.2x106 - 5.9x106) which represents a sufficient depth for digital gene expression profiling of 214 genes. CTAs re-expressed significantly after one AZA cycle in complete responders were TFDP3 (FC=6,4), ZNF645 (FC=2), MAGEB4 (FC=3,1), MAGEA5 (FC=2), DDX53 (FC=2), VENTPX1 (FC=5,5), TSPY2(FC=3,4) and TSYP3 (FC=3,5). Other potential candidates with significantly re-expression in any responders vs. non responder were:SLCO6A1, ADAM29, DDX53, PRAME, FAM46D, TMPRSS12, MAGEA1, MAGEA2, Cxorf48, DANJB8, NYESO-1 and CT83. In the western-blot experiments, protein expression, longitudinally measured in peripheral blood lysate and/or plasma showed a parallel dynamic to gene expression in the case of TFDP3and DDX53. Conclusions:In this study, targeted RNA-seq is shown as effective and accurate tool to detect weakly expressed transcripts as CTAs. In this work, TFDP3 and DDX53, validated at proteomic level, emerge as most promising candidates for immunotherapy in combination with hypomethylating agents in MDS patients. Disclosures No relevant conflicts of interest to declare.
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Bhan, Sheetal, Sandeep S. Negi, Chunbo Shao, Chad A. Glazer, Alice Chuang, Daria A. Gaykalova, Wenyue Sun, David Sidransky, Patrick K. Ha, and Joseph A. Califano. "BORIS Binding to the Promoters of Cancer Testis Antigens, MAGEA2, MAGEA3, and MAGEA4, Is Associated with Their Transcriptional Activation in Lung Cancer." Clinical Cancer Research 17, no. 13 (May 10, 2011): 4267–76. http://dx.doi.org/10.1158/1078-0432.ccr-11-0653.
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Protsenko, S. B., O. S. Novytska, and S. S. Perekhodko. "ОСОБЛИВОСТІ АЕРОДИНАМІЧНОГО РОЗРАХУНКУ ВЕНТИЛЯЦІЙНИХ СИСТЕМ У КОМП’ЮТЕРНІЙ ПРОГРАМІ MAGICAD." Bulletin National University of Water and Environmental Engineering 3, no. 87 (November 29, 2019): 128. http://dx.doi.org/10.31713/vt3201911.
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Методика визначення втрат тиску у програмі MagiCAD суттєво відрізняється від вітчизняної, що необхідно враховувати при виконанні аеродинамічного розрахунку в процесі проектування вентиляційних систем. У статті розглянуті математичні залежності, що використовуються програмою MagiCAD при виконанні аеродинамічного розрахунку мереж повітропроводів, і проведене їх порівнянняз тими, що застосовуються у вітчизняній практиці проектування.Порівняння результатів розрахунків виконані для питомих значеньвтрат тиску на тертя та на подолання місцевих опорів (відводів круглого та прямокутного перерізів, дифузорів та конфузорів, трійників тощо). Попри суттєві відмінності в методиках обчислені значення втрат тиску є доволі близькими, значна різниця результатів розрахунків спостерігалася лише для конфузорів.
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Yu, Yue, Chenjun Huang, Zhihua Li, Fei Zhao, Yue Zhou, Jun Li, Chenxiang Zhu, et al. "Expressions of melanoma-associated antigen A1 as a prognostic factor in Chinese patients with resectable oesophageal squamous cell carcinoma." Interactive CardioVascular and Thoracic Surgery 29, no. 4 (June 6, 2019): 510–16. http://dx.doi.org/10.1093/icvts/ivz141.
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AbstractOBJECTIVESMelanoma-associated antigen A1 (MAGEA1) is a potential target for immunotherapy and has been associated with poor survival rate in several cancers. However, little is known about the prognostic predictive value of MAGEA1 in oesophageal squamous cell carcinoma (OSCC). This study aims to determine whether the expression of MAGEA1 is an independent predictor of survival in patients with resectable OSCC.METHODSA retrospective analysis was performed on a large cohort of 197 patients with OSCC who underwent radical surgical treatment in the Department of Thoracic Surgery between January 2006 and December 2012. The expression of MAGEA1 in OSCC and matched normal oesophageal mucosa specimens from these patients was detected by immunohistochemistry with tissue microarray technology.RESULTSThe MAGEA1 protein was expressed in the cytoplasm and nucleus of tumour cells. The positive expression rate of MAGEA1 was significantly higher in OSCC tissue than in normal oesophageal mucosa (73.6% vs 5.6%, P < 0.001). MAGEA1 expression had no correlations with sex, age, history of smoking, alcohol consumption, family history of upper gastrointestinal cancer, T stage, lymph node metastasis, grade/location of the tumour or TNM stage (all at P > 0.05). Compared with those with negative MAGEA1 expression, patients with positive MAGEA1 expression were associated with a reduced overall survival rate (5-year survival rate: 53.8% vs 37.2%; P = 0.018). The multivariable analysis revealed that MAGEA1 expression is an independent predictor of prognosis (P = 0.007, hazard ratio 1.85, 95% confidence interval 1.19–2.89).CONCLUSIONSThe expression of MAGEA1 is abundant in Chinese patients with OSCC and is related to a worse clinical outcome. MAGEA1 may be a useful prognostic factor in patients with resectable OSCC.
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Ye, Xueting, Jing Xie, Hang Huang, and Zhexian Deng. "Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells." Cellular Physiology and Biochemistry 45, no. 3 (2018): 1205–18. http://dx.doi.org/10.1159/000487452.
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Background/Aims: Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). Methods: MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. Results: MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. Conclusion: MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling.
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Araujo, Dejka M., Mihaela Druta, Mark Agulnik, Sandra P. D'Angelo, Jean-Yves Blay, Sandra J. Strauss, Claudia Valverde, et al. "SPEARHEAD-1: A phase II trial of ADP-A2M4 SPEAR T cells in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): TPS11569. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.tps11569.
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TPS11569 Background: ADP-A2M4 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered to target MAGE-A4+ tumors in the context of HLA-A*02. MAGE-A4 has been described as having high expression in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) [1, 2]. This Phase 2 trial was initiated based on the favorable benefit:risk profile of ADP-A2M4 observed in a Phase 1 trial (NCT03132922) of ADP-A2M4 which demonstrated compelling clinical responses in patients with SS. Methods: This Phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety and tolerability of ADP-A2M4 in patients with advanced/metastatic SS or MRCLS who are HLA-A*02 positive and whose tumors express the MAGE-A4 protein. Enrolled patients are to undergo apheresis, and their isolated T-cells are then transduced with the MAGE-A4c1032 TCR, and expanded. Prior to ADP-A2M4 infusion, patients are to receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m2/day x 4 days) and cyclophosphamide (600 mg/m2/day x 3 days). Patients are to receive 1 – 10 × 109 transduced T-cells. An independent Data Safety Monitoring Board will review ongoing safety and benefit:risk during the interventional phase of the study. Disease will be assessed by independent review per RECIST v1.1 by CT/MRI at weeks 4, 8, 12, 16, 24, and every 2 months thereafter until confirmed disease progression. As of 24 Jan 2020, there were 17 clinical sites open in the US, one in Canada, and two in Spain. References: 1. Iura K, et al. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Human Pathology 2017; 61:130-139. 2. Iura K, et al. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1. Virchows Archiv 2017;471:383–392. Clinical trial information: NCT04044768 .
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Oppermann, Hannes, Felix Wichum, Jens Haueisen, Matthias Klemm, and Lorenz Esch. "MagCPP: A C++ toolbox for Combining Neurofeedback with Magstim transcranial magnetic stimulators." Current Directions in Biomedical Engineering 6, no. 3 (September 1, 2020): 497–500. http://dx.doi.org/10.1515/cdbme-2020-3128.
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AbstractTranscranial magnetic stimulation (TMS) is an established method to treat various neurological diseases, such as depression, Alzheimer’s disease, and tinnitus. New applications for TMS are closed loop neurofeedback (NF) scenarios, which require software control of the TMS system, instead of the currently used manual control. Hence, the MagCPP (https://github.com/MagCPP) toolbox was developed and is described in this work. The toolbox enables the external control of Magstim TMS devices via a C++ interface. Comparing MagCPP to two other toolboxes in a TMS application scenario with 40% power, we found that MagCPP works faster and has lower variability in repeated runs (MagCPP, Python, MATLAB [mean±std in seconds]: 1.19±0.00, 1.59±0.01, 1.44±0.02). An integration of MagCPP in a real-time data processing platform MNE-CPP with an optional GUI demonstrates its ability as part of a closed-loop NF-scenario. With its performing advantages over other toolboxes, MagCPP is a first step towards a complete closed loop NF scenario and offers possibilities for novel study designs.
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Reinsalu, Olavi, Anneli Samel, Elen Niemeister, and Reet Kurg. "MAGEA4 Coated Extracellular Vesicles Are Stable and Can Be Assembled In Vitro." International Journal of Molecular Sciences 22, no. 10 (May 14, 2021): 5208. http://dx.doi.org/10.3390/ijms22105208.
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Extracellular vesicles (EVs) are valued candidates for the development of new tools for medical applications. Vesicles carrying melanoma-associated antigen A (MAGEA) proteins, a subfamily of cancer-testis antigens, are particularly promising tools in the fight against cancer. Here, we have studied the biophysical and chemical properties of MAGEA4-EVs and show that they are stable under common storage conditions such as keeping at +4 °C and −80 °C for at least 3 weeks after purification. The MAGEA4-EVs can be freeze-thawed two times without losing MAGEA4 in detectable quantities. The attachment of MAGEA4 to the surface of EVs cannot be disrupted by high salt concentrations or chelators, but the vesicles are sensitive to high pH. The MAGEA4 protein can bind to the surface of EVs in vitro, using robust passive incubation. In addition, EVs can be loaded with recombinant proteins fused to the MAGEA4 open reading frame within the cells and also in vitro. The high stability of MAGEA4-EVs ensures their potential for the development of EV-based anti-cancer applications.
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Atanackovic, D., N. K. Altorki, Y. Cao, E. Ritter, C. Ferrara, G. Ritter, E. W. Hoffman, C. Bokemeyer, L. J. Old, and S. Gnjatic. "Booster vaccination of non-small cell lung cancer (NSCLC) patients with MAGEA3 protein and AS02B adjuvant." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 3015. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.3015.
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3015 Background: We have previously reported results of a phase II trial of recombinant ProtD/MAGE-3/His (MAGEA3) protein 300μg administered IM every three weeks for 4 doses with or without adjuvant AS02B to NSCLC patients following resection of MAGEA3 positive disease (JI, 172:3289, 2004). We found that the presence of adjuvant was essential for the development of strong humoral and cellular responses against selected MAGEA3 epitopes. Methods: 14 of the original 18 patients received booster vaccinations. Patients who still had no evidence of disease for up to two years after receiving their original MAGEA3 protein regimen (7 in cohort 1 without adjuvant, 7 in cohort 2 with adjuvant), received 4 additional doses of MAGEA3 protein with adjuvant. T cell immunomonitoring was extended to encompass any MAGEA3 epitope using full length antigen, and the scope of analysis of humoral responses was widened. Results: After just one boost injection, 6 of the 7 patients originally vaccinated with MAGEA3 protein plus adjuvant reached the peak of antibody titers to MAGEA3 attained during the first vaccination and went on to develop a stronger response than during the first cycle. In addition, the spectrum of CD4+ and CD8+ T cells against various new and known epitopes widened with booster vaccination. In contrast, only 3/7 patients originally vaccinated with MAGEA3 protein alone seroconverted to low-titered MAGEA3 responses and showed very limited CD4+ and no CD8+ T cell reactivity, despite now receiving antigen in the presence of adjuvant. Conclusions: These results underscore the importance of proper antigen priming using an adjuvant for generating persistent B and T cell memory, allowing for typical booster responses with re-immunization. In contrast, absence of adjuvant at priming may compromise further immunization attempts. These data provide immunological rationale for vaccine design in light of recently reported favorable clinical findings in NSCLC patients following vaccination with MAGEA3 protein plus adjuvant AS02B (GSK, ASCO 2005). No significant financial relationships to disclose.
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Троянчук, Б., and Л. Федік. "Використання САПР у проектуванні систем автоматизації." COMPUTER-INTEGRATED TECHNOLOGIES: EDUCATION, SCIENCE, PRODUCTION, no. 45 (December 23, 2021): 39–43. http://dx.doi.org/10.36910/6775-2524-0560-2021-45-06.
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У статті визначено і досліджено актуальні системи автоматизованого проектування. А також проаналізовано існуючі CAD системи і спрогнозовано розвиток ринку в цій сфері. Викладено особливості проектування систем автоматизації в програмах AutoCAD, Solidworks, LibreCAD, MagiCAD, ZWCAD.
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Almstedt, Maika, Dietmar Pfeifer, and Michael Lubbert. "Cancer Testis Antigens Residing on the X-Chromosome Are Preferentially Derepressed in Myeloid Leukemic Cells by the DNA Demethylating Agent 5-Aza-2’-Deoxycytidine (DAC)." Blood 112, no. 11 (November 16, 2008): 2247. http://dx.doi.org/10.1182/blood.v112.11.2247.2247.
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Abstract Introduction: Azanucleoside DNA demethylating agents upregulate large sets of genes in vitro. Cancer testis antigens (CTAs) are a growing group of immunogenic proteins that provide attractive targets for cancer-specific immunotherapy in solid tumors. In contrast, only a very limited number of studies has been performed on epigenetic regulation of CTAs in myeloid leukemia. A single report suggested specific in vivo induction of CTA mRNAs in blasts from AML and MDS pts treated with intermediate-dose Decitabine (DAC; Sigalotti et al., Blood101:4644–6, 2003). We wished to extend this finding by examining kinetics and spectrum of CTA and leukemia-associated antigen (LAA) regulation by DAC in myeloid cell lines and primary AML blasts. Materials and Methods: Myeloid cell lines were treated over 72 hrs with 50–200 nM DAC. RNA was isolated from peripheral blood blasts of AML pts treated with DAC (135mg/m2 over 72 hours within the 00331 phase II trial) before and during early phase of the treatment (= days 2, 5 from start of DAC) when circulating blasts were still >40% (mean 75%). Expression analyses were performed by Western Blot (NY-ESO-1), qPCR (NY-ESO-1, MAGEA1, MAGEA3, Myeloblastin), and by HG-U133plus 2.0 mRNA microarray. Results: The five myeloid cell lines Kasumi-1, U937, HL60, K562 and NB4 did not express NY-ESO-1 protein. Upon treatment with DAC, NY-ESO-1 was markedly de-repressed in 3/5 cell lines (Kasumi-1, U937, HL60). Induction of expression was dose- and time-dependent, with maximum induction at day 6, and reversible with prolonged culturing up to day 21. No derepression was seen when U-937 and HL-60 were treated with equitoxic low concentrations of cytarabine (not a Dnmt inhibitor). MAGEA1, MAGEA3 and the LAA Myeloblastin (MBN) were also induced by DAC in Kasumi-1, with the strongest effect observed for NY-ESO-1 and the least for MBN (high baseline expression). Expression analyses were extended to all 67 CTAs present on the U133plus array (45 located on the X-chromosome, 22 autosomally), of which 11/67 (17%) were induced >2 fold in Kasumi-1. Notably, all 11 CTA genes were X-chromosomal, whereas 0/22 autosomal CTAs showed reinduction (p= 0.008 by Fisher-Exact test). 2/9 LAA genes (22%) were also reinduced. In primary AML blasts from 9 pts, DAC treatment resulted in >2fold induction of 3 CTAs and 5 LAAs. qPCR demonstrated NY-ESO-1 upregulation in 2/5 patients, with a maximum at day 5 from start of treatment. Conclusions: Marked derepression of NY-ESO-1 and other CTAs by treatment of myeloid cell lines with an azanucleoside DNA demethylating agent occurred preferentially with genes residing on the X chromosome, in line with a major role of DNA methylation for their regulation. Derepression by DAC was also observed in vivo, albeit less marked and occurring early during treatment. One of the therapeutic effects of low-dose DNA demethylating agents on leukemic myeloid blasts may be mediated via upregulation of antigens rendering the malignant cells more immunogenic.
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Stevenson, Mary, Alexis Santana, Nicole Adell Doudican, Theresa N. Canavan, Anna C. Pavlick, and John Carucci. "Outcomes in MAGE+ cutaneous squamous cell carcinoma with perineural invasion treated with surgery followed by postoperative radiation therapy." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e21043-e21043. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e21043.
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e21043 Background: Perineural invasion (PNI) is associated with a high risk for recurrence and metastasis from cutaneous squamous cell carcinoma (cSCC). Recommendations vary regarding use of post-operative radiation therapy (PORT). Biomarkers for poor outcome from cSCC with PNI are lacking. We aimed to evaluate outcomes in high-risk cSCC with PNI treated surgically +/- PORT and to evaluate tissue from the primary tumor to identify biomarkers for highest risk. Methods: We conducted a retrospective chart review of PNI SCC patients seen between 2005 and 2014. We compared outcomes for surgery vs. surgery plus PORT. Gene expression from tumor debulk was evaluated via Nanostring. MAGEA3 function was evaluated using PAM 212 SCC cells in a BALB/c mouse model. CRISPR-Cas9 MAGEA3 PAM 212 knockouts were developed to assess role of MAGEA3 in SCC growth. Results: Thirty-two patients with PNI SCC were identified. All were treated surgically, and 18/32 elected to undergo PORT. Nodal metastases were noted in 5/14 patients who did not undergo PORT, whereas no metastases were noted in any patient who underwent PORT. Thus, surgery plus PORT was associated with better outcome than surgery alone (P < 0.01). Local recurrence was not observed in any patients treated by surgery, including 30 patients treated by Mohs micrographic surgery (MMS). MAGEA3 was highly expressed in PNI SCC. MAGEA3 expression in PAM 212 SCC was associated with tumor growth and increased expression of cyclins A, B, and E. CRISPR-Cas9 MAGEA3 PAM 212 knockouts exhibited reduced growth in BALB/c mice. Conclusions: MAGEA3 expression is increased in human PNI SCC. We can mitigate against worst case outcome with surgery plus PORT. MAGEA3 merits further investigation as a potential biomarker for best candidates for surgery plus PORT.
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Sipos, Júlia. "Szakmaiság politikán innen és túl - aki az 50-es években is gojzer varrott cipőt hordott." Köz-gazdaság 16, no. 2 (June 20, 2021): 248–53. http://dx.doi.org/10.14267/retp2021.02.18.
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2018. április 13-án a Budapesti Corvinus Egyetem Faculty Clubjában Sipos Júlia beszélget Laki Árpáddal, aki vasokleveles egykori hallgató, később állandó oktató volt, nemzedékek számviteli képzése fűződik nevéhez. Csipkedd magad, gólya!
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Craig, Amanda J., Teresa Garcia-Lezana, Marina Ruiz de Galarreta, Carlos Villacorta-Martin, Edgar G. Kozlova, Sebastiao N. Martins-Filho, Johann von Felden, et al. "Transcriptomic characterization of cancer-testis antigens identifies MAGEA3 as a driver of tumor progression in hepatocellular carcinoma." PLOS Genetics 17, no. 6 (June 24, 2021): e1009589. http://dx.doi.org/10.1371/journal.pgen.1009589.
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Cancer testis antigens (CTAs) are an extensive gene family with a unique expression pattern restricted to germ cells, but aberrantly reactivated in cancer tissues. Studies indicate that the expression (or re-expression) of CTAs within the MAGE-A family is common in hepatocellular carcinoma (HCC). However, no systematic characterization has yet been reported. The aim of this study is to perform a comprehensive profile of CTA de-regulation in HCC and experimentally evaluate the role of MAGEA3 as a driver of HCC progression. The transcriptomic analysis of 44 multi-regionally sampled HCCs from 12 patients identified high intra-tumor heterogeneity of CTAs. In addition, a subset of CTAs was significantly overexpressed in histologically poorly differentiated regions. Further analysis of CTAs in larger patient cohorts revealed high CTA expression related to worse overall survival and several other markers of poor prognosis. Functional analysis of MAGEA3 was performed in human HCC cell lines by gene silencing and in a genetic mouse model by overexpression of MAGEA3 in the liver. Knockdown of MAGEA3 decreased cell proliferation, colony formation and increased apoptosis. MAGEA3 overexpression was associated with more aggressive tumors in vivo. In conclusion MAGEA3 enhances tumor progression and should be considered as a novel therapeutic target in HCC.
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Yeoh, C., and C. Chelala. "Molecular analysis of tamoxifen-resistant pathways in breast cancer cell-lines and breast cancer tissues." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22094-e22094. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22094.
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e22094 Background: Oestrogen receptor positive (ER+) breast cancer (BC) is heterogeneous with regard to their clinical behaviour and response. The ER and Progesterone receptors (PgR) are currently the best predictors of response to the anti-oestrogen agent tamoxifen, yet up to 30–40% of ER+ breast cancers will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance is required. There has been an explosion of greater understanding since the arrival of new cutting-edge genomic profiling technology. Methods: RNA from the BC cell lines and frozen tissue was extracted and qualified using Qiagen Mini Kit and BioAgilent respectivelly. Probe preparation and scanning of the chips were carried out according to Affymetrix protocol. The normalisation and analysis of data (Limma) was performed using Bioconductor software. RT- PCR probes were purchased from Applied Biosystem and performed on ABI7500 instrument. The IHC-P was done using Ventana. TMA prepared with TMABooster, Alphelys (Plaisir, France). Results: Gene expression changes were studied in the TR breast cell lines MCF7 (tenovus), T47D and ZR by using the Affymetrix Hu133 plus 2.0 platform. Common genes of significant expression from the 3 TR cell lines were validated by real-time PCR (RT-PCR) and immuno-histochemistry (IHC-P) staining. 7 (MAGEA2, AKR1C3, VGLL1, THRAP5, GREB1, PDZK1, MYBL1, HnRNPA2B1, PGR) out of the 9 chosen genes were successfully validated. Proliferation studies on MageA2 overexpressing clones were performed. Stable overexpression of MageA2 in T47D and MCF-7 confers a proliferation advantage in tamoxifen-containing media as shown in proliferation and cell cycle analysis. MageA2 has been shown to alter the p53 pathway. The expression of KAP1, which interacts with p53 and inactivates it, was enhanced by MageA2 overexpression. In addition, overexpression of MageA2 is seen to increases histone deacetylase (HDAC3), and p53 expression as seen by immunoblotting. Validation of MageA2 on TMA of 100 patients is underway. Conclusions: MageA2 is a possible selective molecular target for the reversal of tamoxifen resistance. No significant financial relationships to disclose.
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Cleto, Sara, and Erin Bahl. "Becoming the Labyrinth: Negotiating Magical Space and Identity in Puella Magi Madoka Magica." Humanities 5, no. 2 (April 6, 2016): 20. http://dx.doi.org/10.3390/h5020020.
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Sellitto, P., G. Dufour, M. Eremenko, J. Cuesta, G. Forêt, B. Gaubert, M. Beekmann, V. -H Peuch, and J. M. Flaud. "Monitoring the lowermost tropospheric ozone with thermal infrared observations from a geostationary platform: performance analyses for a future dedicated instrument." Atmospheric Measurement Techniques Discussions 6, no. 4 (July 15, 2013): 6445–90. http://dx.doi.org/10.5194/amtd-6-6445-2013.
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Abstract. In this paper, we present performance analyses for a concept geostationary observing system called MAGEAQ (Monitoring the Atmosphere from Geostationary orbit for European Air Quality). The MAGEAQ mission is designed to include a TIR spectrometer and a broadband VIS radiometer; in this work we study only the TIR component (MAGEAQ-TIR). We have produced about 20 days of MAGEAQ-TIR tropospheric ozone pseudo-observations with a full forward and inverse radiative transfer pseudo-observations simulator. We have studied the expected sensitivity of MAGEAQ-TIR and we have found that a completely independent surface −6 km ozone column (about 1.0 DOF (degrees of freedom) and maximum sensitivity at about 3.0 km, on average), as well as a partially independent surface −3 km ozone column (about 0.6 DOF and maximum sensitivity at about 2.5 km, on average) can be achieved. Then, we have compared the tropospheric ozone profiles and the lower (surface −6 km) and lowermost (surface −3 km) tropospheric ozone column pseudo-observations to the target pseudo-reality, produced with the MOCAGE (MOdèle de Chimie Atmosphérique à Grande Echelle) chemistry and transport model. We have found very small to not significant average biases (< 1% in absolute value, for the surface −6 km TOC, and about −2 to −3%, for the surface −3 km TOC) and small RMSEs (about 1.3 DU (5%), for the surface −6 km TOC, and about 1.5 DU (10%), for the surface −3 km TOC). We have tested the performances of MAGEAQ-TIR at some selected small (0.2° × 0.2°) urban and rural locations. We have found that, while the vertical structures of the lower tropospheric ozone pseudo-reality are sometimes missed, MAGEAQ-TIR lower and lowermost column pseudo-observations follow stunningly good the MOCAGE column pseudo-reality, with correlation coefficients reaching values of 0.9 or higher. Unprecedented retrieval performances for the lowermost tropospheric ozone column are shown. In any case, our MAGEAQ-TIR pseudo-observations are only partially able to replicate the MOCAGE pseudo-reality variability and temporal cycle at the very lowest layers (surface and 1 km altitude), especially at Southern European urban locations, where the photochemistry signal is partially missed or shifted at higher altitudes. Temporal artifact on the daily cycle are sometimes observed. Stratospheric-to-tropospheric exchanges during short time periods (of the order of 1 day) are detected by the MAGEAQ-TIR pseudo-observations.
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Leet, Kennie, Tim K. Lowenstein, Robin W. Renaut, R. Bernhart Owen, and Andrew Cohen. "Labyrinth patterns in Magadi (Kenya) cherts: Evidence for early formation from siliceous gels." Geology 49, no. 9 (June 3, 2021): 1137–42. http://dx.doi.org/10.1130/g48771.1.
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Abstract Sedimentary cherts, with well-preserved microfossils, are known from the Archean to the present, yet their origins remain poorly understood. Lake Magadi, Kenya, has been used as a modern analog system for understanding the origins of nonbiogenic chert. We present evidence for synsedimentary formation of Magadi cherts directly from siliceous gels. Petrographic thin-section analysis and field-emission scanning electron microscopy of cherts from cores drilled in Lake Magadi during the Hominin Sites and Paleolakes Drilling Project in 2014 led to the discovery of two-dimensional branching “labyrinth patterns” in chert, which are a type of fractal “squeeze” pattern formed at air-liquid interfaces. Labyrinth patterns preserved in chert from Lake Magadi cores indicate invasion of air along planes in dewatering gels. These patterns support the precipitation of silica gels in the saline-alkaline Lake Magadi system and syndepositional drying of gels in contact with air as part of chert formation. Recognizing cherts as syndepositional has been critical for our use of them for U-Th dating. Identification of labyrinth patterns in ancient cherts can provide a better understanding of paleoenvironmental and geochemical conditions in the past.
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Goodyear, Oliver Charles, Angelo Agathanggelou, Gordon Ryan, Igor Novitsky-Basso, Tatjana Stankovic, Paul Moss, and Charles F. Craddock. "The Epigenetic Therapies Azacitidine and Sodium Valproate Augment Immune Responses to the MAGE Cancer Testis Antigen in Acute Myeloid Leukemia and Myeloma." Blood 114, no. 22 (November 20, 2009): 2086. http://dx.doi.org/10.1182/blood.v114.22.2086.2086.
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Abstract Abstract 2086 Poster Board II-63 The mechanism by which epigenetic therapies exert an anti-tumor effect in Acute Myeloid Leukemia (AML) and myeloma is unknown. We have studied immune responses to cancer testis antigens (CTA) a family of immunodominant tumor-associated antigens, in 12 patients with AML treated with the DNA methyltransferase inhibitor 5-Azacitidine (AZA) and the histone deacetylase inhibitor sodium valproate (VPA). The frequency of CTA-specific CD8+ T cells was studied in 12 patients with high risk AML prior to treatment with AZA (75 mg/m2 × 7 days per 28 day cycle) and sodium valproate (1-2.5 g daily administered continuously as tolerated) on a Phase II clinical trial. CTA specific CTLs were detectable in 4 of 12 patients with relapsed AML undergoing treatment with AZA and VPA. In one patient CTLs specific to the peptide MAGE-A2157-166 were detectable prior to commencement of trial therapy at a frequency of 0.001%.and persisted throughout treatment. In three patients CTLs were only detectable after commencement of AZA therapy. A polyclonal T cell line was subsequently generated from one patient and tetramer staining of the line revealed the presence of 1% MAGE-A2157-166-specific T cells and this could be enriched using anti-PE magnetic beads (Miltenyi Biotec). Two patients in whom AZA induced a CTL response to MAGE achieved a partial response to trial therapy by Cheson criteria. Treatment with AZA resulted in up to 100fold increased levels of expression of MAGEA4, MAGEA1, HAGE, SSX1, NY ESO1, MAGEC1, LAGE and XAGE mRNA in AML cell lines: HL60, KG1a, U937 and NB4 and multiple myeloma cell lines: U266 and JJN3. We next studied whether prior treatment with AZA augmented recognition of hematopoietic tumors by MAGE specific T cell clones. Prior treatment with AZA increased recognition of two myeloma cell lines (JJN3 and U266) by a MAGEA1 specific T cell clone. This is the first demonstration that AZA induce a CTL response to MAGE in patients with AML. Taken together our data are consistent with the possibility that epigenetic manipulation of cancer testis antigen expression and induction of a tumor specific CTL response may contribute to the clinical activity of AZA in hematologic malignancies. Disclosures: No relevant conflicts of interest to declare.
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Sellitto, P., G. Dufour, M. Eremenko, J. Cuesta, G. Forêt, B. Gaubert, M. Beekmann, V. H. Peuch, and J. M. Flaud. "Monitoring the lowermost tropospheric ozone with thermal infrared observations from a geostationary platform: performance analyses for a future dedicated instrument." Atmospheric Measurement Techniques 7, no. 2 (February 6, 2014): 391–407. http://dx.doi.org/10.5194/amt-7-391-2014.
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Abstract. In this paper, we present performance analyses for a concept geostationary observing system called MAGEAQ (Monitoring the Atmosphere from Geostationary orbit for European Air Quality). The MAGEAQ mission is designed to include a TIR (thermal infrared) spectrometer and a broadband VIS (visible) radiometer; in this work we study only the TIR component (MAGEAQ-TIR). We have produced about 20 days of MAGEAQ-TIR tropospheric ozone pseudo-observations with a full forward and inverse radiative transfer pseudo-observations simulator. We have studied the expected sensitivity of MAGEAQ-TIR and we have found that it is able to provide a full single piece of information for the ozone column from surface to 6 km (about 1.0 DOF (degrees of freedom) and maximum sensitivity at about 3.0 km, on average), as well as a partially independent surface–3 km ozone column (about 0.6 DOF and maximum sensitivity at about 2.5 km, on average). Then, we have compared the tropospheric ozone profiles and the lower (surface–6 km) and lowermost (surface–3 km) tropospheric ozone column pseudo-observations to the target pseudo-reality, produced with the MOCAGE (MOdèle de Chimie Atmosphérique à Grande Echelle) chemistry and transport model. We have found very small to not significant average biases (< 1% in absolute value, for the surface–6 km TOC (tropospheric ozone column), and about −2 to −3 %, for the surface–3 km TOC) and small RMSEs (root mean square errors; about 1.3 DU (5%), for the surface–6 km TOC, and about 1.5 DU (10%), for the surface–3 km TOC). We have tested the performance of MAGEAQ-TIR at some selected small (0.2° × 0.2°) urban and rural locations. We have found that, while the vertical structures of the lower tropospheric ozone pseudo-reality are sometimes missed, MAGEAQ-TIR's lower and lowermost column pseudo-observations follow stunningly good the MOCAGE column pseudo-reality, with correlation coefficients reaching values of 0.9 or higher. Unprecedented retrieval performance for the lowermost tropospheric ozone column is shown. In any case, our MAGEAQ-TIR pseudo-observations are only partially able to replicate the MOCAGE pseudo-reality variability and temporal cycle at the very lowest layers (surface and 1 km altitude), especially at southern European urban locations, where the photochemistry signal is partially missed or shifted at higher altitudes. Temporal artifacts on the daily cycle are sometimes observed. Stratospheric-to-tropospheric exchanges during short time periods (of the order of 1 day) are detected by the MAGEAQ-TIR pseudo-observations.
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Muzraeva, Delyash N. "Некоторые вопросы исследования сочинения «Sumagadha-avadāna» в отечественном и зарубежном востоковедении (на материале «Легенды о Сайн Магаде» из Монгольского Ганджура)." Oriental studies 15, no. 4 (November 15, 2022): 731–39. http://dx.doi.org/10.22162/2619-0990-2022-62-4-731-739.
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Introduction. The Sumagadha-Avadāna (‘Avadāna of Sumagadha’) is often mentioned in Oriental studies, including works on the history of classical Mongolian literature examining writings of Indo-Tibetan origin. This text is included in both the Tibetan- and Mongolian-language canonical Kangyur (Kanjur) editions. Despite frequent references, the former has neither been translated into Russian, nor there are any descriptions of its structure and content. Goals. So, the article attempts to fill the gap and aims at considering the narrative about Sayin Magada through the analysis of The Legend of Sayin Magada (Mong. Sayin Magada-yin domuγ), the latter being integral to the canonical collection of Kanjur in Mongolian. The work explores the text, describes its genre characteristics, identifies its structure, reveals contents, and investigates data contained in the colophon. Materials. The study focuses on the text titled ‘Sayin Magada-yin domuγ-i ögülegči kemekü’ (‘[Sutra] Narrating the Legend of Sayin Magada’) from the Eldeb (‘Collection of Sutras’) section of the Mongolian Kanjur (vol. 91). Results. The textual and content analysis of works by Tibetologists, Mongolists, and Sinologists dealing with writings of the avadāna genre included in the canon makes it possible to reveal key characteristics of the genre, describe the structure of the Mongolian text, and outline its content.
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Muzraeva, Delyash N. "Некоторые вопросы исследования сочинения «Sumagadha-avadāna» в отечественном и зарубежном востоковедении (на материале «Легенды о Сайн Магаде» из Монгольского Ганджура)." Oriental studies 15, no. 4 (November 15, 2022): 731–39. http://dx.doi.org/10.22162/2619-0990-2022-61-4-731-739.
Full textAbstract:
Introduction. The Sumagadha-Avadāna (‘Avadāna of Sumagadha’) is often mentioned in Oriental studies, including works on the history of classical Mongolian literature examining writings of Indo-Tibetan origin. This text is included in both the Tibetan- and Mongolian-language canonical Kangyur (Kanjur) editions. Despite frequent references, the former has neither been translated into Russian, nor there are any descriptions of its structure and content. Goals. So, the article attempts to fill the gap and aims at considering the narrative about Sayin Magada through the analysis of The Legend of Sayin Magada (Mong. Sayin Magada-yin domuγ), the latter being integral to the canonical collection of Kanjur in Mongolian. The work explores the text, describes its genre characteristics, identifies its structure, reveals contents, and investigates data contained in the colophon. Materials. The study focuses on the text titled ‘Sayin Magada-yin domuγ-i ögülegči kemekü’ (‘[Sutra] Narrating the Legend of Sayin Magada’) from the Eldeb (‘Collection of Sutras’) section of the Mongolian Kanjur (vol. 91). Results. The textual and content analysis of works by Tibetologists, Mongolists, and Sinologists dealing with writings of the avadāna genre included in the canon makes it possible to reveal key characteristics of the genre, describe the structure of the Mongolian text, and outline its content.
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Iura, Kunio, Akira Maekawa, Kenichi Kohashi, Takeaki Ishii, Hirofumi Bekki, Hiroshi Otsuka, Yuichi Yamada, et al. "Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1." Human Pathology 61 (March 2017): 130–39. http://dx.doi.org/10.1016/j.humpath.2016.12.006.
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Walsh, P. J., H. L. Bergman, A. Narahara, C. M. Wood, P. A. Wright, D. J. Randall, J. N. Maina, and P. Laurent. "EFFECTS OF AMMONIA ON SURVIVAL, SWIMMING AND ACTIVITIES OF ENZYMES OF NITROGEN METABOLISM IN THE LAKE MAGADI TILAPIA OREOCHROMIS ALCALICUS GRAHAMI." Journal of Experimental Biology 180, no. 1 (July 1, 1993): 323–27. http://dx.doi.org/10.1242/jeb.180.1.323.
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The Lake Magadi tilapia, Oreochromis alcalicus grahami, is remarkable among teleosts in that it flourishes under extremely well-buffered alkaline water conditions (pH 10, CCO2 180 mmol l-1) at temperatures of 30–40 °C (Wood et al. 1989). As expected from current models in teleosts, ammonia excretion into such water would be difficult at best (Wood, 1993). Part of the survival strategy of the Lake Magadi tilapia is that it has a complete ornithine-urea cycle (O-UC) in the liver and excretes virtually all of its waste nitrogen as urea (Randall et al. 1989). Ammonia toxicity in ammoniotelic teleosts has been studied extensively, and typical values for unionized ammonia (NH3) 96 h LC50 (the concentration at which half of test subjects die after 96 h) are well below 100 micromolar (Haywood, 1983; Thurston et al. 1983a,b; Campbell, 1991). Surprisingly, no ammonia LC50 values are available for ureogenic teleost fish, and one would predict that fish synthesizing and excreting urea for whatever purpose would have higher LC50 values than their ammoniotelic counterparts. Additionally, since ammonia exposure has been implicated in the functional response of urea excretion in the Lake Magadi tilapia (Wood et al. 1989) and another ureogenic teleost (the gulf toadfish Opsanus beta) (Walsh et al. 1990), we reasoned that ammonia exposure in the Lake Magadi tilapia might reveal insights into the biochemical regulation of the O-UC in this species; in particular that it might induce enzyme activity. We report here that the Lake Magadi tilapia has a rather high ammonia LC50 compared to values for other teleosts, but that short-term ammonia exposure has very limited effects on the activities of the enzymes of nitrogen metabolism and on swimming performance.
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Reinhardt, Manuel, Walter Goetz, Jan-Peter Duda, Christine Heim, Joachim Reitner, and Volker Thiel. "Organic signatures in Pleistocene cherts from Lake Magadi (Kenya) – implications for early Earth hydrothermal deposits." Biogeosciences 16, no. 12 (June 19, 2019): 2443–65. http://dx.doi.org/10.5194/bg-16-2443-2019.
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Abstract. Organic matter in Archean hydrothermal cherts may provide an important archive for molecular traces of the earliest life on Earth. The geobiological interpretation of this archive, however, requires a sound understanding of organic matter preservation and alteration in hydrothermal systems. Here we report on organic matter (including molecular biosignatures) enclosed in hydrothermally influenced cherts of the Pleistocene Lake Magadi (Kenya; High Magadi Beds and Green Beds). The Magadi cherts contain low organic carbon (< 0.4 wt %) that occurs in the form of finely dispersed clots, layers, or encapsulated within microscopic carbonate rhombs. Both extractable (bitumen) and non-extractable organic matter (kerogen) were analyzed. The bitumens contain immature “biolipids” like glycerol mono- and diethers (e.g., archaeol and extended archaeol), fatty acids, and alcohols indicative for, inter alia, thermophilic cyanobacteria, sulfate reducers, and haloarchaea. However, co-occurring “geolipids” such as n-alkanes, hopanes, and polycyclic aromatic hydrocarbons (PAHs) indicate that a fraction of the bitumen has been thermally altered to early or peak oil window maturity. This more mature fraction likely originated from defunctionalization of dissolved organic matter and/or hydrothermal petroleum formation at places of higher thermal flux. Like the bitumens, the kerogens also show variations in thermal maturities, which can partly be explained by admixture of thermally pre-altered macromolecules. However, findings of archaea-derived isoprenoid moieties (C20 and C25 chains) in kerogen pyrolysates indicate rapid sequestration of some archaeal lipids into kerogen while hydrothermal alteration was active. We posit that such early sequestration may enhance the resistance of molecular biosignatures against in situ hydrothermal and post-depositional alteration. Furthermore, the co-occurrence of organic matter with different thermal maturities in the Lake Magadi cherts suggests that similar findings in Archean hydrothermal deposits could partly reflect original environmental conditions and not exclusively post-depositional overprint or contamination. Our results support the view that kerogen in Archean hydrothermal cherts may contain important information on early life. Our study also highlights the suitability of Lake Magadi as an analog system for hydrothermal chert environments on the Archean Earth.
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Sallay, Viola, and Andrea Dúll. "„Érezd magad otthon!”." Magyar Pszichológiai Szemle 61, no. 1 (March 1, 2006): 35–52. http://dx.doi.org/10.1556/mpszle.61.2006.1.3.
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A helyidentitás és a helykötodés eredeti fogalmának sokat vitatott jellemzoje az egyértelmuen pozitív érzelmi töltés. A kilencvenes években a kutatások ebben a szellemben zajlottak, ami fokozódó feszültséget teremtett az otthon környezetpszichológiai elméletei és ezek gyakorlati alkalmazása között. Az utóbbi idokben egyre több vizsgálat foglalkozik azokkal a helyzetekkel, amelyekben az otthoni helyidentitásnak eredetileg tulajdonított pozitív töltés valamilyen okból nem lelheto fel, illetve eros negatív színezetet kap. Ezek mögött a helyzetek mögött a családi élet zavarai, traumái, normatív és paranormatív krízisei állnak. Az újabb kutatások kimutatják, hogy azok az otthonok, amelyekhez negatív élmények kapcsolódnak, pszichológiailag ugyanannyira jelentoségteljesek, mint azok, amelyek pozitív módon a szükségletek kielégítését szolgálják. Az otthonhoz fuzodo érzelmi viszony így lényegét tekintve összetett, adott esetben ambivalens. A jelen tanulmányban az otthonhoz fuzodo viszony feltáró jellegu, projektív vizsgálatának általunk kidolgozott módszerét, a módszer kialakítása keretében zajlott résztvevo fotózás eljárását és a kvalitatív adatok (fényképek) feldolgozásának eredményeit mutatjuk be.
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Sakimpa, Keponyi, Dr Willy M. Muturi, and Dr Mos Otieno. "EFFECT OF RAILWAY NETWORK INEFFICIENCIES ON BUSINESS OPERATIONS OF TATA CHEMICALS MAGADI, MOMBASA IN KENYA." International Journal of Business Strategies 1, no. 1 (October 11, 2016): 26. http://dx.doi.org/10.47672/ijbs.38.
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Purpose: The purpose of this study was to investigate the effect of railway network inefficiencies on business operations of Tata chemicals Magadi, Mombasa in Kenya.Methodology: This study adopted a descriptive survey design. The target population of this study was the 450 employees of TATA Chemical Magadi Ltd. The study used a sample of 135 employees. The study employed stratified random sampling to identify the 135 respondents. The strata were those of top management, middle management/supervisors and non-managerial employees. Primary data was used to gather information by use of questionnaires. Information was sorted, coded and input into the statistical package for social sciences (SPSS 20) for production of descriptive and inferential statistics.Results: Results on the analysis of variance showed that the overall model was statistically significant and that the independent variables were good predictors of performance. This was supported by an F statistic of 71.69 and the reported p value (0.000) which was less than the conventional probability of 0.05significance level. Descriptive results indicated that inefficiencies of Kenya Railway Corporation greatly affect production targets, customer satisfaction, sales targets and equipment utilization in Tata chemicals Magadi Ltd which in turn affects the performance of the company.Unique contribution to theory, practice and policy: The government should allocate additional annual budget to the Kenya Railways Corporation to provide efficient means of transporting freight between cities and towns. Additionally, management of Tata Chemicals Magadi Ltd should exercise stronger leadership to enhance long term planning and disaster management to avoid loss to customers and manage its efficiency.
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Laurent, Pierre, J. N. Maina, Harold L. Bergman, Annie Narahara, Patrick J. Walsh, and Chris M. Wood. "Gill structure of a fish from an alkaline lake: effect of short-term exposure to neutral conditions." Canadian Journal of Zoology 73, no. 6 (June 1, 1995): 1170–81. http://dx.doi.org/10.1139/z95-139.
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The morphology and morphometry of the gills of Oreochromis alcalicus grahami, a unique ureogenic teleost that lives in the alkaline environment of Lake Magadi, Kenya (pH 10, [Formula: see text], temperature 30 – 40 °C) were examined by transmission electron, scanning electron and light microscopy. Fish were examined in normal Lake Magadi water and 2 – 3 or 24 h after transfer to Lake Magadi water neutralized to pH 7 with HCl (i.e., [Formula: see text] replaced with Cl−), a treatment that caused severe reductions in urea excretion and O2 uptake, internal acidosis, and ionoregulatory disturbance. In Lake Magadi water, the organization of the filament epithelium of the gill was similar to that of sea water teleosts. Indeed, chloride cells were located at the bottom of pits bordered by overlying pavement cells and flanked by typical accessory cells. Total numbers of chloride cells remained unchanged after transfer to pH 7, but after 2 – 3 h, many were covered by pavement cells, restricting their communication with the external milieu. At 24 h, this trend was reversed, an observation indicative of a reactivation of chloride cells. Mucous cells were located at maximum density on the trailing edge of the filament; most of them were empty after 24 h at pH 7. The harmonic mean thickness of the lamellar epithelium (blood-to-water diffusion pathway) was very small and not altered by acute or longer term exposure to pH 7. A model of alterations in ion and acid – base transport accompanying the morphological changes is presented.
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Cooley. "A Cycle, Not a Phase: Love Between Magical Girls Amidst the Trauma of Puella Magi Madoka Magica." Mechademia: Second Arc 13, no. 1 (2020): 24. http://dx.doi.org/10.5749/mech.13.1.0024.
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Nauck, Matthias, Markus Nauck, and Jochem Koetting. "A Recapping System for Automatic, Semiautomatic, and Manual Use." Archives of Pathology & Laboratory Medicine 132, no. 4 (April 1, 2008): 690–93. http://dx.doi.org/10.5858/2008-132-690-arsfas.
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Abstract Context.—Closed sample tubes are needed for stored as well as in-process samples because evaporation significantly changes analyte concentrations. In modern laboratories, it is essential that the procedures for ordering tests on stored serum samples be simple and time-efficient. Therefore, recapping and reopening of tubes should be readily possible in laboratories to save resources and time. Objective.—To evaluate the recapping system MagCap, in comparison to established snap caps and unsealed tubes. Design.—Specific balls, with an iron core, fit tightly by their specific weight into openings of primary and secondary tubes as well as microtiter plates. Recapping of the tubes can be performed individually by a single dispenser or rackwise by a multidispenser. Balls can be removed individually by a pencillike magnet or rackwise. Balls can be reused after cleaning in a glassware washer or used as disposables. Results.—Balls seal the sample tubes as effectively as snap caps and decrease evaporation significantly in comparison to unsealed tubes. Evaporation effects of up to 13% were detected in unsealed tubes (0.5 mL) within 24 hours, whereas resealing of the tubes diminished the concentration effect to less than 1%. Open samples (0.5 mL) showed a concentration effect in the refrigerator within 7 days of up to 25%. The evaporation effect of the sealed tubes was less than 3%. Multiple reopenening and recapping procedures are easily possible using magnetic forces. Conclusions.—The MagCap recapping system seals primary and secondary containers securely and cost-effectively with the ball cap and thus facilitates a necessary advance in sample quality.
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SMITH, GIDEON F. "Aloe davyana var. magdae (Asphodelaceae subfam. Alooideae), a distinctive new variety from central-northeastern South Africa." Phytotaxa 536, no. 3 (February 28, 2022): 261–69. http://dx.doi.org/10.11646/phytotaxa.536.3.6.
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Following the reinstatement of Aloe davyana as an accepted taxon at the rank of species, rather than at that of variety under A. greatheadii, and the subsequent reinstatement of A. davyana var. subolifera, a new variety, A. davyana var. magdae, is here described. Aloe davyana var. magdae, from the southern part of the distribution range of the species, inter alia differs from the pale flesh-pink to dull brick-red-flowered autonymic variety by being more intensely red-flowered, while the other, north-central variety, A. davyana var. subolifera, is most often nearly white-flowered. In addition, the new variety has about twice as many leaves per rosette, in comparison to the autonymic variety and A. davyana var. subolifera.
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Chari, Ajai, Hearn J. Cho, Amishi Dhadwal, Gillian Morgan, Lisa La, Katarzyna Zarychta, Donna Catamero, et al. "A phase 2 study of panobinostat with lenalidomide and weekly dexamethasone in myeloma." Blood Advances 1, no. 19 (August 21, 2017): 1575–83. http://dx.doi.org/10.1182/bloodadvances.2017007427.
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Pšenáková, Ildikó. "Ne hagyd magad becsapni!" Lélektan és hadviselés 2, no. 1 (2020): 55–65. http://dx.doi.org/10.35404/lh.2020.1.55.
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Hemminger, Jessica A., Amanda Ewart Toland, Thomas J. Scharschmidt, Joel L. Mayerson, Denis C. Guttridge, and O. Hans Iwenofu. "Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma." Modern Pathology 27, no. 9 (January 24, 2014): 1238–45. http://dx.doi.org/10.1038/modpathol.2013.244.
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Mujianto, Agustinus, and Antonius Denny Firmanto. "Katekese Keluarga pada Masa Pandemi Covid 19 dalam Perspektif Model Katekese Ritual Maggid." Jurnal Ledalero 20, no. 1 (September 1, 2021): 19. http://dx.doi.org/10.31385/jl.v20i1.230.19-34.
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<p><em>This paper aims to provide new insights on the importance of family catechesis during the Covid 19 pandemic. During the Covid 19 pandemic, religious activities have been eliminated or restricted. Normally, Catholics can celebrate worship at church, but that will no longer be possible after the government prohibits gathering to prevent the transmission of the Coronavirus. Therefore, this situation hinders the formation of the faith of the people. Then, there was a shift in the celebration of faith which was originally held in the church to be carried out in the family during the Covid 19 pandemic. Therefore, family catechesis in this regard plays an important role in the celebration of faith within the family itself. The methodology is a qualitative method. The data were collected from books, news, and journals. For data analysis, this study used a deductive method with maggid ritual catechesis model as a perspective. This study found that family catechesis with the maggid ritual catechesis model can answer what the Catholic family missed during the Covid 19 pandemic, namely the celebration of togetherness, the experience of community faith, internalization, and transformation. </em></p><p><strong><em>Key words</em></strong><em>: Catechesis, Faith Celebration, Family, Maggid Ritual</em></p>
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Wu, Long, Huan Zhang, Yixing Jiang, Robert C. Gallo, and Hua Cheng. "Induction of antitumor cytotoxic lymphocytes using engineered human primary blood dendritic cells." Proceedings of the National Academy of Sciences 115, no. 19 (April 19, 2018): E4453—E4462. http://dx.doi.org/10.1073/pnas.1800550115.
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Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+/CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs). In an autologous setting, the HLA-A2+ ihv-DCs that present hTERT antigen prime autologous T cells to generate hTERT-specific CTLs, inducing cytolysis of hTERT-expressing target cells in an HLA-A2–restricted manner. Remarkably, ihv-DCs that carry two allogeneic HLA-DRB1 alleles are able to prime autologous T cells to proliferate robustly in generating HLA-A2–restricted, hTERT-specific CTLs. The ihv-DCs, which are engineered to express MAGEA3 and high levels of 4-1BBL and MICA, induce simultaneous production of both HLA-A2–restricted, MAGEA3-specific CTLs and NK cells from HLA-A2+ donor peripheral blood mononuclear cells. These cytotoxic lymphocytes suppress lung metastasis of A549/A2.1 lung cancer cells in NSG mice. Both CTLs and NK cells are found to infiltrate lung as well as lymphoid tissues, mimicking the in vivo trafficking patterns of cytotoxic lymphocytes. This approach should facilitate the development of cell-based immunotherapy for human lung cancer.
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Owen, R. Bernhart, Veronica M. Muiruri, Tim K. Lowenstein, Robin W. Renaut, Nathan Rabideaux, Shangde Luo, Alan L. Deino, et al. "Progressive aridification in East Africa over the last half million years and implications for human evolution." Proceedings of the National Academy of Sciences 115, no. 44 (October 8, 2018): 11174–79. http://dx.doi.org/10.1073/pnas.1801357115.
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Evidence for Quaternary climate change in East Africa has been derived from outcrops on land and lake cores and from marine dust, leaf wax, and pollen records. These data have previously been used to evaluate the impact of climate change on hominin evolution, but correlations have proved to be difficult, given poor data continuity and the great distances between marine cores and terrestrial basins where fossil evidence is located. Here, we present continental coring evidence for progressive aridification since about 575 thousand years before present (ka), based on Lake Magadi (Kenya) sediments. This long-term drying trend was interrupted by many wet–dry cycles, with the greatest variability developing during times of high eccentricity-modulated precession. Intense aridification apparent in the Magadi record took place between 525 and 400 ka, with relatively persistent arid conditions after 350 ka and through to the present. Arid conditions in the Magadi Basin coincide with the Mid-Brunhes Event and overlap with mammalian extinctions in the South Kenya Rift between 500 and 400 ka. The 525 to 400 ka arid phase developed in the South Kenya Rift between the period when the last Acheulean tools are reported (at about 500 ka) and before the appearance of Middle Stone Age artifacts (by about 320 ka). Our data suggest that increasing Middle- to Late-Pleistocene aridification and environmental variability may have been drivers in the physical and cultural evolution of Homo sapiens in East Africa.
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Poulsen, Rolf. "Magical." Wilmott 2020, no. 110 (November 2020): 30–33. http://dx.doi.org/10.1002/wilm.10884.
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Lingán, Jorge, and Thomas B. Croat. "NEW SPECIES OF ANTHURIUM (ARACEAE) FROM THE PERUVIAN ANDES." Rodriguésia 56, no. 88 (September 2005): 43–51. http://dx.doi.org/10.1590/2175-78602005568805.
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ABSTRACT Five new species of Anthurium are described from Peru: Anthurium chinchipense Croat & Lingán, A. hamiltonii Croat & Lingán, A. magdae Croat & Lingán, A. mariae Croat & Lingán, and A. piurensis Croat & Lingán.
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Conte, Aida, Daniela Maria Dolfi, Mario Gaeta, Valeria Misiti, Silvio Mollo, and C. r. i. s. t. i. n. a. Perinelli. "Experimental constraints on evolution of leucite-basanite magma at 1 and 10-4GPa: implications for parental compositions of Roman high-potassium magmas." European Journal of Mineralogy 21, no. 4 (August 31, 2009): 763–82. http://dx.doi.org/10.1127/0935-1221/2009/0021-1934.
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Danyi, Gábor, and András Vigvári. "Magad uram, ha szolgád nincs." Replika 110 (June 1, 2019): 83–92. http://dx.doi.org/10.32564/110.3.
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