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Rahardjani, Kamilah Budhi. "Hubungan antara Malondialdehyde (MDA) dengan Hasil Luaran Sepsis Neonatorum." Sari Pediatri 12, no. 2 (2016): 82. http://dx.doi.org/10.14238/sp12.2.2010.82-7.
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Latar belakang. Sepsis merupakan penyebab morbiditas dan mortalitas terbanyak pada neonatus. Pada sepsis terjadi peningkatan stres oksidatif yang menyebabkan kerusakan jaringan dan hemolisis. Kadar MDA serum merupakan biomarker adanya stress oksidatif.Tujuan. Mengetahui hubungan antara MDA serum dengan hasil luaran sepsis pada neonatus.Metode. Penelitian observasional prospektif dilakukan pada neonatus sepsis yang dirawat di PBRT (Peawatan Bangsal Risiko Tinggi) RSUP Dr. Kariadi Semarang, Oktober 2007 sampai dengan Januari 2008. Diagnosis sepsis berdasar gejala klinik dan pemeriksaan laboratorium. Keluaran sepsis dikelompokkan menjadi dua yaitu perburukan (BR) dan perbaikan (BI). Kadar MDA serum diukur dua kali saat terdiagnosis sepsis (MDA1) dan pada hari ke-5 atau bila terjadi disfungsi organ / meninggal / perburukan (MDA2) dengan menggunakan metode spektofotometri. Analisis statistik menggunakan Uji Wilcoxon Signed – Rank, Mann-Whitney, ROC analysis dan Fisher-exact.Hasil. Subjek penelitian terdiri dari 41 neonatus sepsis, 33 neonatus BI dan 8 neonatus BR. Rerata kadar MDA1 2,97±0,14 dan MDA2 3,05±0,34. Kadar MDA 1 kelompok BI 2,95±0,117, kelompok BR 3,08±0,172 (p=0,03). Kadar MDA2 kelompok BI 2,97±0,182, kelompok BR 3,38±0,591 (p=0,006). Kelompok BI MDA2 meningkat tak bermakna (p=0,9), kelompok BR, MDA2 meningkat bermakna (p=0,01). Kurva ROC luas area bawah kurva MDA1 0,75 (p=0,03), cut-off-point= 2,928 ng/mL. Dijumpai hubungan bermakna antara kategori MDA1 dengan luaran sepsis (p=0,02). Risiko relatif MDA1 ≥2,928 ng/mL untuk hasil luaran sepsis perburukan 7,4 X (95% CI=1,4-37,2).Kesimpulan. Terdapat hubungan antara kadar MDA serum dengan hasil luaran sepsis neonatorum. (
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Sahlström, P., M. Gomes Afonso, V. Joshua, et al. "POS0004 PRO-INFLAMMATORY ANTI-MODIFIED PROTEIN AUTOANTIBODIES DERIVED FROM BONE MARROW, SYNOVIAL, AND LUNG B CELLS PREFERENTIALLY TARGET MALONDIALDEHYDE-ACETALDEHYDE CROSS-LINKED MOLECULAR STRUCTURES." Annals of the Rheumatic Diseases 82, Suppl 1 (2023): 207.1–207. http://dx.doi.org/10.1136/annrheumdis-2023-eular.4681.
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BackgroundAutoantibodies to malondialdehyde (MDA) proteins constitute a subset of anti-modified protein autoantibodies (AMPA) in rheumatoid arthritis (RA), which is not directly overlapping with citrulline reactivity. We have previously shown that IgM anti-MDA is prominent in the natural antibody repertoire at birth and may have homeostatic roles. Yet, IgG anti-MDA is elevated in RA and correlates with DAS28, CRP, IL6 and TNF-α [1]. Moreover, RA-derived anti-MDA monoclonal antibodies induce bone erosion and osteoclastogenesis by modulating cell metabolism [2]. MDA is an oxidation-associated reactive aldehyde that together with acetaldehyde (AA) mediates formation of a range of amino acid adducts including linear MDA-lysine, fluorescent MAA-lysine, and intramolecular cross-linking. MDA/MAA proteins carry multiple adduct-variants, and we here propose that distinct subsets of anti-MDA/MAA antibodies, defined based on the MDA-induced molecular structures recognized, have different pathogenic properties. Moreover, we have investigated the presence of class-switched MDA+ B cells in RA synovium, bone marrow, and bronchoalveolar lavage (BAL).ObjectivesIdentification of RA MDA+ B cells from different compartments and distinct MDA/MAA reactivity patterns.MethodsHuman recombinant mAbs were generated from single-cell sorted B cells from BAL and bone marrow (n=148) and screened for reactivity to MDA and MAA modified antigens. MDA-cyanoborohydride and MDA/MAA-hapten proteins without cross-linking were used for characterization. Serology screening of IgG reactivity to MAA-BSA was performed as previously described [3].ResultsIgG MAA-reactivity is elevated in 49% of ACPA+ RA patients (n=278) compared to 14% of population controls (n=437). We did not detect any significant increase in IgG anti-MAA in ACPA+ RA-risk individuals at baseline,14% had high anti-MAA (n=263), compared to controls. But for risk-individuals that developed arthritis, anti-MAA levels increased at onset of arthritis with 26% displaying elevated levels (n=53). We identified IgG+ MDA+ cells among RA bone marrow plasma cells and BAL B cells from both early RA and ACPA+ RA-risk, which could be compared to three previously identified RA synovial clones. Seven out of eight investigated clones carried somatic hypermutations (SHM). Interestingly, all clones with SHM were found to specifically target MAA cross-linked structures rather than MDA- or MAA-hapten, while the germline-encoded synovial clone F04 bound strongly to linear MDA-lysine in proteins and peptides. Germline converting resulted in reduced MDA/MAA binding, suggesting different origin of the clones compared to F04. All binding was independent of protein backbone. Yet, only a subset of MAA-selective clones with SHM induced robust TNF-α expression in monocyte-derived macrophages and enhanced osteoclastogenesis.ConclusionMDA/MAA positive B cells can be identified in bone marrow and synovium in established RA and in the lungs of early and RA-risk individuals, but serum levels are only increased in conjunction with onset of arthritis and with inflammation. SHM and class-switching suggest affinity maturation and T-cell dependence of these responses. Distinct targeting of different MDA/MAA molecular structures was observed. Future studies will elucidate how MDA recognition patters are related to the anti-MDA inflammatory and bone-modulating properties and disease stages.References[1]Grönwall, C., et al J Autoimmun. 2017 84:29-45[2]Sakuraba, K., et al J Autoimmun. 2022 133:102903[3]Grönwall, C., et al Front Immunol. 202112:627986Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Sakuraba, K., A. Krishnamurthy, A. Circiumaru, et al. "SAT0017 METABOLIC CHANGES INDUCED BY ANTI-MALONDIALDEHYDE/MALINDIALDEHYDE-ACETALDEHYDE ANTIBODIES PROMOTE OSTEOCLAST DEVELOPMENT." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 938.2–939. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5013.
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Background:Malondialdehyde (MDA) is a highly reactive compound produced by lipid-peroxidation in situations associated with oxidative stress. MDA can irreversibly modify proteins residues such as lysine, arginine and histidine. In addition, MDA adducts can further react with acetaldehyde to generate malondialdehyde-acetaldehyde (MAA) modifications. Such modifications can give rise to immunogenic neo-epitopes that are recognized by autoantibodies. In fact, anti-MDA/MAA IgG antibodies are significantly increased in the serum of patients with autoimmune diseases, such as rheumatoid arthritis (RA) (1) and systemic lupus erythematosus (2). Recently, we have shown that anti-MDA/MAA IgG antibodies are able to promote osteoclast (OC) differentiationin vitro(1).Objectives:To investigate the molecular mechanisms triggered by anti-MDA/MAA autoantibodies during osteoclastogenesis.Methods:OCs were generated from monocyte-derived macrophages in the presence of the cytokines RANK-L and M-CSF. The development of OCs was monitored by light microscopy following tartrate-resistant acid phosphatase (TRAP) staining and erosion area on synthetic calcium phosphate-coated plates. Three different recombinant human monoclonal anti-MDA/MAA antibodies, cloned from single synovial B cells of RA patients, control antibodies and Fab fragments of the antibodies were added to OC cultures. Glycolysis was inhibited by 2-deoxyglucose, and Fc-gamma receptor I or II by anti-CD64 or anti-CD16 neutralizing antibodies. IL-8 levels were measured by enzyme linked immunosorbent assay. Cellular metabolism was monitored using Seahorse XF Analyzer (extracellular acidification rate and oxygen consumption) and a colorimetric L-Lactate assay.Results:Lactic acid production correlated with the osteoclastogenetic effect of some but not all anti-MDA/MAA antibodies on OCs (R=0.4758, p=0.0252) suggesting an antibody-mediated regulation of glycolysis. Further, extracellular acidification (ECAR) and oxygen consumption (OCR) rate of the developing OCs were increased by the osteoclastogenic anti-MDA/MAA clones (maximum increase of 54% for the ECAR and 78% for the OCR by clone 146+:01G07, and maximum increase of 28% for the ECAR and 39% for the OCR by clone 1103:01H05), but not by the non-osteoclastogenetic anti-MDA/MAA clones or control antibodies. The glycolysis inhibitor 2-deoxyglucose completely abolished the osteoclastogenetic effect of the anti-MDA/MAA clones at drug concentrations that did not influenced baseline OC development. Fab2 fragments of the osteocalstogenetic anti-MDA/MAA clones had no effect on OC development and metabolism. In accordance with this, Fc-gamma receptor I neutralizing antibodies completely abolished the osteocalstogenetic effect of the anti-MDA/MAA clones. The osteoclastogenetic effect of the anti-MDA/MAA antibodies was independent of IL-8 production. In contrast to anti MDA/MAA antibodies, ACPA-mediated osteoclastogenesis was independent of glycolysis and Fc-gamma receptors but dependent on IL-8.Conclusion:Our results describe a novel glycolysis-dependent mechanism by which anti-MDA/MAA antibodies promote osteoclast development that is different from the one previously described for ACPA.References:[1] C. Grönwall et al. Journal of Autoimmunity 84 (2017) 29-45.[2] C. Wang et al. Arthritis and Rheumatism 62 (2010) 2064-2072Disclosure of Interests:Koji Sakuraba: None declared, Akilan Krishnamurthy: None declared, Alexandra Circiumaru: None declared, Meng Sun: None declared, Vijay Joshua: None declared, Marianne Engström: None declared, Xiaowei Zheng: None declared, Cheng Xu: None declared, Khaled Amara: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica, Sergiu-Bogdan Catrina: None declared, Caroline Grönwall: None declared, Bence Réthi: None declared, Anca Catrina: None declared
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Bowo, Prasetyo, Sumarmi Sumarmi, and Sri Hardiatmi. "PENERAPAN MACAM DAN DOSIS PUPUK ORGANIK TERHADAP PERTUMBUHAN DAN HASIL TANAMAN GANDUM (Triticum aestivum L.)." Innofarm:Jurnal Inovasi Pertanian 21, no. 1 (2019): 1. http://dx.doi.org/10.33061/innofarm.v21i1.3311.
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Penelitian tentang “Penerapan macam dan dosis pupuk organik terhadap pertumbuhan dan hasil tanaman Gandum (Triticum aestivum L.)’’ telah dilaksanakan tanggal 08 November 2018 sampai 31 januari 2019 di Green House Fakultas Pertanian Universitas Slamet Riyadi Surakarta. Penelitian ini bertujuan untuk mengetahui dan menentukan pengaruh terbaik terhadap pertumbuhan dan hasil tanaman gandum. Rancangan penelitian yang digunakan adalah rancangan acak lengkap yang terdiri dari 7 perlakuan dan 5 ulangan. Perlakuan : 1) MD0 = tanpa pupk (kontrol), 2) MD1= pupuk kandang dosis 200 g/polybag, 3) MD2 = pupuk kandang dosis 400 g/polybag , 4) MD3 = pupuk guano dosis 200 g/polybag, 5) MD4 = pupuk guano dosis 400 g/polybag, 6) MD5 = pupuk kascing dosis 200 g/polybag, 7) MD6 = pupuk kascing dosis 400 g/polybag. Hasil penelitian menunjukkan bahwa : 1) penerapan macam dan dosis pupuk organik berpengaruh terhadap tinggi tanaman, jumlah daun, dan jumlah anakan, 2) penerapan macam dan dosis pupuk organik tidak berpengaruh terhadaap berat segar brangkasan, berat kering brangkasan, jumlah biji, berat biji, dan berat 100 biji, 3) macam dan dosis pupuk terbaik adalah MD2 (pupuk kandang dosis 400 g/polybag) karena dapat meningkatkan jumlah daun dan jumlah anakan.
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Sakuraba, K., A. Krishnamurthy, A. Circiumaru, et al. "POS0400 METABOLIC CHANGES INDUCED BY ANTI-MALONDIALDEHYDE/MALINDIALDEHYDE-ACETALDEHYDE ANTIBODIES PROMOTE OSTEOCLAST DEVELOPMENT." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 429. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3678.
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Background:Malondialdehyde (MDA) is a highly reactive compound generated during lipid-peroxidation in conditions associated with oxidative stress. MDA can irreversibly modify proteins (e.g. lysine, arginine and histidine residues). In addition, acetaldehyde can further react with MDA adducts to form malondialdehyde-acetaldehyde (MAA) modification. Such protein modifications can lead to immunogenic neo-epitopes that are recognized by autoantibodies. In fact, anti-MDA/MAA IgG antibodies are significantly increased in the serum of patients with autoimmune diseases, such as rheumatoid arthritis (RA) (1). Interestingly, anti-MDA/MAA antibodies have been shown to promote osteoclast (OC) differentiation in vitro suggesting a potential role for these autoantibodies in bone damage associated with RA (1).Objectives:Little is known about the molecular mechanisms activated by autoantibodies in RA. Here, we elucidate the pathways specifically triggered by anti-MDA/MAA autoantibodies in developing osteoclasts.Methods:Recombinant human monoclonal anti-MDA/MAA antibodies, which were previously cloned from single synovial B cells of RA patients, were added to different OC assays. OCs were generated from monocyte-derived macrophages in the presence of the cytokines RANK-L and M-CSF. OC development was monitored by light microscopy following tartrate-resistant acid phosphatase staining and by erosion assays using calcium phosphate-coated plates. Bone morphometrics were studied in anti-MDA/MAA-injected mice using X-ray microscopy. Cellular metabolism was analyzed by mass spectrometry, Seahorse XF Analyzer and a colorimetric L-Lactate assay.Results:Anti-MDA/MAA antibodies induced a robust OC differentiation in vitro and bone loss in vivo. The anti-MDA/MAA antibodies acted on developing OCs by increasing glycolysis via an Fcγ receptor I-mediated pathway and the upregulation of the transcription factors HIF-1α, Myc and CHREBP. Such regulation of cellular metabolism was exclusively observed in the presence of the osteoclastogenic anti-MDA/MAA clones, whereas other RA-associated autoantibodies (anti-MDA/MAA or anti-citrullinated protein antibodies) had no effect on metabolism. The anti-MDA/MAA treatment induced a shift in the tricarboxylic acid (TCA) cycle activity in developing OCs, leading to the accumulation of citrate and aconitate.Conclusion:We described a novel type of autoantibody-induced pathway in RA, which might contribute to increased OC activation and a consequent bone loss. Anti-MDA/MAA antibodies promoted osteoclast development by increasing glycolysis and by modulating the TCA cycle through a signaling pathway that included Fcγ receptor I and a network of transcription factors acting on glycolysis. A TCA cycle bias towards citrate production suggests that the anti-MDA/MAA antibodies might stimulate OCs via increasing lipid biosynthesis in the cells.References:[1]Grönwall C. et al. J. Autoimmunity 84 (2017): 29-45.Acknowledgements:This Project has received funding from FOREUM, Foundation for Research in Rheumatology, from the European Research Council (ERC) grant agreement CoG 2017 - 7722209_PREVENT RA, the EU/EFPIA Innovative Medicine Initiative grant agreement 777357_RTCure, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse and Knut and Alice Wallenberg Foundation.Disclosure of Interests:Koji Sakuraba: None declared, Akilan Krishnamurthy: None declared, Alexandra Circiumaru: None declared, Vijay Joshua: None declared, Heidi Wähämaa: None declared, Marianne Engström: None declared, Meng Sun: None declared, Xiaowei Zheng: None declared, Cheng Xu: None declared, Khaled Amara: None declared, Vivianne Malmström Grant/research support from: collaboration with Pfizer, unrelated to the abstract, Sergiu-Bogdan Catrina: None declared, Caroline Grönwall: None declared, Bence Réthi: None declared, Anca Catrina Grant/research support from: collaboration with BMS and Pfizer, unrelated to the present abstract
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Lu, Na, Junji Li, Changwei Bi, et al. "ChimeraMiner: An Improved Chimeric Read Detection Pipeline and Its Application in Single Cell Sequencing." International Journal of Molecular Sciences 20, no. 8 (2019): 1953. http://dx.doi.org/10.3390/ijms20081953.
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As the most widely-used single cell whole genome amplification (WGA) approach, multiple displacement amplification (MDA) has a superior performance, due to the high-fidelity and processivity of phi29 DNA polymerase. However, chimeric reads, generated in MDA, cause severe disruption in many single-cell studies. Herein, we constructed ChimeraMiner, an improved chimeric read detection pipeline for analyzing the sequencing data of MDA and classified the chimeric sequences. Two datasets (MDA1 and MDA2) were used for evaluating and comparing the efficiency of ChimeraMiner and previous pipeline. Under the same hardware condition, ChimeraMiner spent only 43.4% (43.8% for MDA1 and 43.0% for MDA2) processing time. Respectively, 24.4 million (6.31%) read pairs out of 773 million reads, and 17.5 million (6.62%) read pairs out of 528 million reads were accurately classified as chimeras by ChimeraMiner. In addition to finding 83.60% (17,639,371) chimeras, which were detected by previous pipelines, ChimeraMiner screened 6,736,168 novel chimeras, most of which were missed by the previous pipeline. Applying in single-cell datasets, all three types of chimera were discovered in each dataset, which introduced plenty of false positives in structural variation (SV) detection. The identification and filtration of chimeras by ChimeraMiner removed most of the false positive SVs (83.8%). ChimeraMiner revealed improved efficiency in discovering chimeric reads, and is promising to be widely used in single-cell sequencing.
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Oida, Yasuhisa, Began Gopalan, Ryo Miyahara, et al. "Sulindac enhances adenoviral vector expressing mda-7/IL-24–mediated apoptosis in human lung cancer." Molecular Cancer Therapeutics 4, no. 2 (2005): 291–304. http://dx.doi.org/10.1158/1535-7163.291.4.2.
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Abstract Several studies have shown antitumor activities of the melanoma differentiation–associated gene 7 (mda-7) and the nonsteroidal anti-inflammatory drug sulindac when used as a monotherapies against a wide variety of human cancers. However, the combined effects of mda-7 and sulindac have not previously been tested. Therefore, we tested the antitumor activity of an adenoviral vector expressing mda-7 (Ad-mda7) in combination with sulindac against non–small cell lung cancer cells in vitro and in vivo. When treated with Ad-mda7 in combination with sulindac, human lung cancer cells (A549 and H1299) underwent growth suppression resulting in apoptosis. The growth inhibition induced by Ad-mda7 in combination with sulindac was significantly greater than that observed with Ad-mda7 or sulindac alone. Furthermore, the degree of growth inhibition induced using this combination was dose-dependent for sulindac. Treatment with Ad-mda7 in combination with sulindac had no growth inhibitory effects on human normal lung (CCD-16) fibroblasts. We then investigated the mechanism by which sulindac enhances Ad-mda7-mediated apoptosis. Sulindac increased expression of ectopic MDA-7 protein in tumor cells, thereby increasing the expression of downstream effectors RNA-dependent protein kinase, p38MAPK, caspase-9, and caspase-3 and enhancing apoptosis of non–small cell lung cancer cells. Pulse-chase experiments showed that the increased expression of MDA-7 protein in sulindac-treated cells was due to increased half-life of the MDA-7 protein. Finally, treatment of human lung tumor xenografts in nude mice with Ad-mda7 plus sulindac significantly suppressed growth (P = 0.001) compared with Ad-mda7 or sulindac alone. Our results show for the first time that combined treatment with Ad-mda7 plus sulindac enhances growth inhibition and apoptosis of human lung cancer cells. The increased antitumor activity observed with the combination treatment is a result of increased half-life of MDA-7 protein. Regulation of protein turnover is a heretofore-unrecognized mechanism of this nonsteroidal anti-inflammatory drug.
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Lee, Seung-Han, and Jae-Pyo Park. "A Case Study of Software Development Quality Improvement by Agile Methodology and MDA/MDD Technology." Journal of the Korea Academia-Industrial cooperation Society 16, no. 4 (2015): 2744–48. http://dx.doi.org/10.5762/kais.2015.16.4.2744.
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Hayati, Alfiah, Soesanto Mangkoewidjojo, Aucky Hinting, and Sukarti Moeljopawiro. "HUBUNGAN KADAR MDA SPERMA DENGAN INTEGRITAS MEMBRAN SPERMATOZOA TIKUS (Rattus norvegicus) SETELAH PEMAPARAN 2–METHOXYETHANOL." Berkala Penelitian Hayati 11, no. 2 (2006): 151–54. http://dx.doi.org/10.23869/bphjbr.11.2.20069.
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In the body, 2-methoxyethanol compound may be converted to MAA. MAA is a strong oxidant and may cause oxidation stress in spermatozoa. Oxidation stress is a disturbance on phosphorilation that increases ROS concentration, and it produces lipid peroxide in spermatozoa membrane resulted in high MDA concentration. One of indicator of spermatozoa membrane disturbances is a lack of spermatozoa membrane integrity. The main purpose of this research was to determine the relationship between MDA concentration in sperm and membrane integrity of spermatozoa in rats. The animal of treated groups (n = 40) were divide into 8 groups of 5 each. The rats were given subcutaneous injection with 0,2 ml of 200 mg/kg/day for 1 day (P1), 3 days (P2), 6 days/week (P3), and 12 days/two weeks (P4), respectively the control group was injected with physiological saline of the same volume. The concentration of MDA was measured by spectrophotometer and observing membrane integrity used HOS method to watch the spermatozoa response on hypoosmotic condition. The results of the research indicated that 2-ME caused the increasing in sperm MDA concentration and the decrease of spermatozoa membrane integrity. There was negative correlations between MDA concentration and spermatozoa membrane integrity.
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Ellerhorst, Julie A., Victor G. Prieto, Suhendan Ekmekcioglu, et al. "Loss of MDA-7 Expression With Progression of Melanoma." Journal of Clinical Oncology 20, no. 4 (2002): 1069–74. http://dx.doi.org/10.1200/jco.2002.20.4.1069.
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PURPOSE: Ectopic transfer of the melanoma differentiation-associated gene-7 (mda-7) has been shown in vitro to suppress growth and induce apoptosis in a variety of human tumor cell lines; similar effects are not elicited in normal cells. Thus, the mda-7 gene seems to function as a novel tumor suppressor, and there is interest in the potential of mda-7 gene transfer as cancer therapy. The objective of this study was to determine if MDA-7 protein is lost during primary melanoma progression from superficial to invasive stages and from localized to metastatic tumor. As a secondary objective, we analyzed MDA-7 protein expression in primary melanomas for correlation with predictors of outcome and with survival. MATERIALS AND METHODS: MDA-7 protein expression was evaluated by immunohistochemistry in 41 primary melanomas and 41 metastases, including 24 paired samples. Each sample was scored for the percentage of positive cells and the overall intensity of immunolabeling. RESULTS: Significant decreases in MDA-7 immunostaining, reflected in both number and intensity scores, were observed when comparing the intraepidermal and superficially invasive portions with the deeply invasive portions of primary tumors. Significant differences were also observed when comparing primary tumors to paired metastases. CONCLUSION: Downregulation of MDA-7 expression in primary melanomas facilitates progression to invasive and metastatic stages. These data support the development of Ad-mda7 as gene therapy for advanced melanoma.
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Šilingas, Darius. "MD3 – integruotas modeliavimu pagrįstas duomenų projektavimas objektinėms, XML ir sąryšinių duomenų bazių technologijoms." Informacijos mokslai 50 (January 1, 2009): 301–5. http://dx.doi.org/10.15388/im.2009.0.3222.
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Modeliais pagrįstos architektūros (MDA) paradigma siūlo didinti programinės įrangos kūrimo efektyvumą keliant abstrakcijos lygį. Tuo tikslu siūloma kaip pagrindinę programų konstravimo priemonę naudoti ne tekstines programavimo kalbas, o vizualiasmodeliavimo kalbas, tokias kaip UML. Šiame straipsnyje nagrinėjamas MDA taikymas duomenų struktūrų projektavimui. Pristatomas MD3 metodikos karkasas, kuris apibrėžia duomenų projektavimo principus, veiksmų seką, UML poaibį, skirtą duomenims modeliuoti, UML plėtinius XML schemoms ir DDL kodui reprezentuoti, transformacijas tarp skirtingų duomenų abstrakcijos lygių bei duomenų struktūrų projektavimui specializuotą modeliavimo aplinką. MD3 taikymas iliustruojamas nedideliais, bet reprezentatyviais pavyzdžiais iš bibliotekos dalykinės srities. Pristatomas MD3 metodikos karkasas suvokiamas kaip pradinis atspirties taškas labiau specializuotiems ar formalizuotiemsų duomenų projektavimo metodams ir įrankiams kurti.MD3 – Integrated Model-Driven Data Design for Objects, XML, and Relational Databases Darius Šilingas SummaryThe Model-Driven Architecture (MDA) paradigm promotes raising the level of abstraction and development effi ciency by leveraging visual modeling instead of textual programming as the main means for producing software artifacts. In this paper, we focus on applying the MDA approach to data design. We introduce an integrated model-driven data design (MD3) framework, which consists of the data design workfl ow defi nition, a small subset of UML for conceptual data modeling, UML profi les for representing XML and relational database schemas, verifi cation rules for checking model completeness and correctness, transformations between data design abstraction layers, and a customized integrated modeling environment. Application of the MD3 framework is illustrated by a small representative data design sample from the library domain. The MD3 framework is a conceptual starting point for developing more specialized and formalized data design methods and tools.
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Ichimori, Kazuyo. "MDA—Lymphatic Filariasis." Tropical Medicine and Health 42, no. 2SUPPLEMENT (2014): S21—S24. http://dx.doi.org/10.2149/tmh.2014-s03.
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MIMURA, Keiji, Susumu YUKAWA, Akira HIBINO, and Hiroshi NOMOTO. "Heterogeneity of MDA-rich LDL." Journal of Japan Atherosclerosis Society 18, no. 9-10 (1990): 793–802. http://dx.doi.org/10.5551/jat1973.18.9-10_793.
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Mosquera Martínez, J. A., C. García-Porrúa, L. Fernández-Dominguez, J. L. Guerra-Vazquez, and J. Pinto-Tasende. "AB0823 MINIMAL DISEASE ACTIVITY IN PSORIATIC ARTHRITIS IS ASSOCIATED WITH LOW IMPACT OF DISEASE ON PSAID12 QUESTIONAIRE." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1715.2–1715. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4722.
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Background:Psoriatic arthritis (PsA) has a prevalence of 0.58% in Spain and patients suffer this disease have significant impact on daily life due to articular, dermatological and psychological symptoms. To reach minimal disease activity (MDA) is a therapeutic goal recommended by EULAR for clinical practice.Objectives:Our aim was to assess the relationship between MDA and PsAID questionnaire in routine clinical practice.Methods:We performed a cross-sectional study of patient and physician reported outcomes. We obtained clinical information of patients with PsA attending clinic from October 2018 to October 2019. Data were collected from clinical records concerning age, gender, disease duration, joint counts, dactylitis, enthesitis, body surface area (BSA) of psoriasis, laboratory results (ESR and CRP), HAQ, PsAID12, pain and global assessment from patient with numerical rating scale (NRS) and MDA status. Data were analysed using SPSS21. Logistic regression was used to assess patient reported outcomes which were associated with achieving MDA.Results:Data were available for 210 patient visits, 57% males. MDA 5/7 was reached in 118 patients (56.2%) and MDA7/7 in 58 (27.6%). Age and gender were not associated with reach MDA. Higher disease duration was associated with MDA, OR 1.062 (1.012-1.114, 95% CI), p 0.015.PsAID12 was evaluated in 156 patients and all components were associated with reach MDA. Patients in MDA had significantly lower PsAID12 than those were not in MDA (mean 1.5 ± SD 1.5 vs. 3.8 ± 2.1), p< 0.0001. PsAID12 of less than 4 is considered a good outcome and individual components of PsAID12 (Figure 1, mean values for NRS) were less than 4 in patients with MDA.Figure 1.All components of PsAID12 were associated with MDA on univariate analysis but only pain and functional capacity remained independent predictors on multiple regression analysis (p< 0.0001 and p0.008 respectively).Percentage of BSA was associated with skin component of PsAID12 (p<0.0001) and with shame component (p0.001).Conclusion:In these PsA patients, MDA was reached mainly in patients with higher disease duration. MDA is a relevant treatment target in PsA, with markedly lower PsAID12 in patients in MDA. Pain and functional discapacity are dominant symptoms in patients with psoriatic arthritis, even in those in MDA. Skin affection is associated with skin and shame components on the PsAID12.References:[1]Queiro R et al. Arthritis Res Ther. 2017 Mar 29;19(1):72.Acknowledgments:SOGAREDisclosure of Interests:José Antonio Mosquera Martínez: None declared, Carlos García-Porrúa: None declared, Luis Fernández-Dominguez: None declared, Jose L. Guerra-Vazquez: None declared, Jose Pinto-Tasende Consultant of: Janssen, Novartis, Speakers bureau: Lilly, Janssen, Novartis, BMS, Pfizer, Celgene
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Crampton, Steve, Jonathan Deane, Karen Hasty, Owokunile Otubusin, and Silvia Bolland. "Transgenic Expression of the RNA-sensing Molecule MDA-5 Accelerates Autoimmunity in the Lupus-prone FcgammaR2-Deficient Mouse (93.20)." Journal of Immunology 184, no. 1_Supplement (2010): 93.20. http://dx.doi.org/10.4049/jimmunol.184.supp.93.20.
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Abstract Nucleic-acid sensing molecules provide a first line of defense against microbial infections, but recent studies have shown that their inappropriate activation could promote autoimmunity. MDA-5 senses virally-derived RNA in the cytoplasm, which leads to type one interferon (IFN) production, recently shown to be associated with systemic lupus erythematosus. Here, we have generated mice with multiple copies of Ifih1, the gene that encodes MDA-5, and crossed them to the lupus-prone FcgammaRIIB-/- mouse. Mice with enhanced MDA-5 expression and FcgammaRIIB deficiency have accelerated autoimmunity with splenomegaly and anti-nuclear antibodies in their serum compared to FcgammaRIIB-deficient mice alone. They also display elevated levels of splenic plasma and germinal center B cells, indicating possible early autoreactive B cell formation. Bone marrow and splenic macrophage/monocytes from MDA5 transgenic animals also display an activated phenotype, characterized by elevated Ly6A/E, PDCA-1 and CD80 expression. B cells from MDA-5-transgenic animals also express elevated levels of type one IFN signature genes. These results suggest that increased expression of MDA-5 could exacerbate lupus, possibly through the early production of type one IFN.
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Makris, P. E., D. A. Tsakiris, A. Papadopoulos, and A. Balias. "The Ratio MDA/MDAa as a New Index of Platelet Hyperactivity." Pathophysiology of Haemostasis and Thrombosis 15, no. 5 (1985): 331–36. http://dx.doi.org/10.1159/000215168.
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Peng, Shouxian, Weiguang Wang, Rong Ling, Shechang Zou, Dongping Li, and Hong Guo. "Human YTH Domain Family 2 (YTHDF2)-Dependent N6-Methyladenosine Mediates Cerebral Ischemia/Reperfusion Injury via Oxidative Stress." Journal of Biomedical Nanotechnology 20, no. 5 (2024): 842–48. http://dx.doi.org/10.1166/jbn.2024.3828.
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Our study aimed to explore whether YT521-B homology domain family protein 2 (YTHDF2)-dependent m6A is involved in oxidative stress induced by I/R in vitro. We established a cell model of I/R by oxygen-glucose deprivation/re-oxygenation (OGD/R) in HT22 cell line. The shRNAs were used to silence YTHDF2 and Nrf2. The expression of YTHDF2 and Nrf2, levels of m6A, and the indicators related to oxidative stress (GSH, SOD and MDA) was detected in different cell groups. CCK8, flow cytometry, and ki67 fluorescence staining was used to evaluate the cell viability and apoptosis. The levels of YTHDF2, m6A and MDA were increased in cells, while the levels of GSH and SOD were reduced by OGD/R. Also, the apoptosis in cells was increased after OGD/R, and with decreased cell viability. The knockdown of YTHDF2 could reduce the level of m6A, increase the expression of Nrf2. Moreover, the levels of GSH and SOD were increased after exposure to YTHDF2-shRNA, while the level of MDA was decreased, and the cell viability was increased. Our study showed that YTHDF2-Dependent N6A mediates cerebral I/R injury via oxidative stress in vitro, which may constitute a new target for stroke.
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Hsissou, Rachid, and Ahmed Elharfi. "Rheological behavior of three polymers and their hybrid composites (TGEEBA/MDA/PN), (HGEMDA/MDA/PN) and (NGHPBAE/MDA/PN)." Journal of King Saud University - Science 32, no. 1 (2020): 235–44. http://dx.doi.org/10.1016/j.jksus.2018.04.030.
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Chen, Bing, Zhao-Hui Hou, Zhe Dong, and Chun-Dong Li. "Crocetin Downregulates the Proinflammatory Cytokines in Methylcholanthrene-Induced Rodent Tumor Model and Inhibits COX-2 Expression in Cervical Cancer Cells." BioMed Research International 2015 (2015): 1–5. http://dx.doi.org/10.1155/2015/829513.
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The effect of crocetin (C20H24O4) on methylcholanthrene- (MCA-) induced uterine cervical cancer in mice was studied in this paper. After the mice were treated orally with crocetin, maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) were examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase (iNOS) activation inHeLacells was analyzed using fluorescence microscopy for light microscopic examination. The MCA mice showed a significant increase in plasma MDA, PMN, IL-1β, TNF-α, and nitrates levels. At the same time, the mRNA level of COX-2 inHeLacells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent.
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Song, Yujin, Eun-Joo Lee, and Deok-Soo Han. "Design Mobile Cross Framework Based MDA." Journal of Korea Multimedia Society 19, no. 8 (2016): 1445–52. http://dx.doi.org/10.9717/kmms.2016.19.8.1445.
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Poitou, Pierre, Benoît Maillet, Lynda Brugallet-Collet, Bruno Burban, Patrick Cottin, and Georges Picherot. "« Va à la MDA »." Adolescence 80, no. 2 (2012): 349. http://dx.doi.org/10.3917/ado.080.0349.
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Djuric, Dragan, Dragan Gaševi, and Vladan Devedžic. "Ontology Modeling and MDA." Journal of Object Technology 4, no. 1 (2005): 109. http://dx.doi.org/10.5381/jot.2005.4.1.a3.
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Verdickt, Tom, Bart Dhoedt, and Frank Gielen. "Incorporating SPE into MDA." ACM SIGSOFT Software Engineering Notes 29, no. 1 (2004): 120–24. http://dx.doi.org/10.1145/974043.974063.
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Kusters, E. "Biological monitoring of MDA." Occupational and Environmental Medicine 49, no. 1 (1992): 72. http://dx.doi.org/10.1136/oem.49.1.72.
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Djuric, Dragan. "MDA-based ontology infrastructure." Computer Science and Information Systems 1, no. 1 (2004): 91–116. http://dx.doi.org/10.2298/csis0401091d.
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The paper presents Ontology Definition Metamodel (ODM) and Ontology UML Profile that enables using Model Driven Architecture (MDA) standards in ontological engineering. Other similar metamodels are based on ontology representation languages, such as RDF(S), DAML+OIL, etc. However, none of these other solutions uses the recent W3C effort-The Web Ontology Language (OWL). In our approach, we firstly define the ODM and Ontology UML Profile place in the context of the MDA four-layer architecture and identify the main OWL concepts. Then, we define ODM using Meta-Object Facility (MOF). The relations between similar MOF and OWL concepts are discussed in order to show their differences (e.g. MOF or UML Class and OWL Class). The proposed ODM is used as a starting point for defining Ontology UML profile that enables using the well-known UML notation in ontological engineering more extensively.
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Philley, Julie V., Anbarasu Kannan, and Santanu Dasgupta. "MDA-9/Syntenin Control." Journal of Cellular Physiology 231, no. 3 (2015): 545–50. http://dx.doi.org/10.1002/jcp.25136.
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Fettke, Peter, and Peter Loos. "Model Driven Architecture (MDA)." Wirtschaftsinformatik 45, no. 5 (2003): 555–59. http://dx.doi.org/10.1007/bf03250921.
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Al-Rashed, Fatema, Reeby Thomas, Areej Al-Roub, Fahd Al-Mulla, and Rasheed Ahmad. "LPS Induces GM-CSF Production by Breast Cancer MDA-MB-231 Cells via Long-Chain Acyl-CoA Synthetase 1." Molecules 25, no. 20 (2020): 4709. http://dx.doi.org/10.3390/molecules25204709.
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Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a monomeric glycoprotein that has been implicated in the tumor growth and progression of different types of cancer. GM-CSF is produced by various non-immune cells including MDA-MB-231 in response to various stimuli. However, the role of lipopolysaccharide (LPS) in the regulation of GM-CSF in MDA-MB-231 breast cancer cells so far remains unclear. Herein, we asked whether LPS could induce GM-CSF production in MDA-MB-231 cells, and if so, which signaling pathway was involved. MDA-MB-231 cells were treated with LPS or tumor necrosis factor alpha (TNF-α; positive control), and GM-CSF expression levels were determined by qRT-PCR, ELISA, and confocal microscopy. Phosphorylation of the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-kB) signaling proteins were evaluated by flow cytometry. Our results show that LPS induces GM-CSF expression at both mRNA and protein levels in MDA-MBA-231 cells. Inhibition of acyl-CoA synthetase 1 (ACSL1) activity in the cells with triacsin C significantly reduces the secretion of GM-CSF. Furthermore, the inhibition of ACSL1 activity significantly blocks the LPS-mediated phosphorylation of p38 MAPK, MEK1/2, extracellular signal-regulated kinase (ERK)1/2, c-Jun NH2-terminal kinase (JNK), and nuclear factor-κB (NF-kB) in the cells. These findings provide the first evidence that LPS induces ACSL1-dependent GM-CSF gene expression in MDA-MB-231 breast cancer cells, which requires the activation of p38 MAPK, MEK1/2, ERK1/2, JNK, and NF-kB.
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Alrashed, Fatema, Reeby Thomas, Areej Al-Roub, Fahd AL-Mulla, and Rasheed Ahmad. "LPS Induces GM-CSF Production by Breast Cancer MDA-MB-231 Cells via Long-Chain Acyl-CoA Synthetase 1." Journal of Immunology 206, no. 1_Supplement (2021): 56.20. http://dx.doi.org/10.4049/jimmunol.206.supp.56.20.
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Abstract Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a monomeric glycoprotein that has been implicated in the tumor growth and progression of different types of cancer. GM-CSF is produced by various non-immune cells including MDA-MB-231 in response to various stimuli. However, the role of lipopolysaccharide (LPS) in the regulation of GM-CSF in MDA-MB-231 breast cancer cells so far remains unclear. Herein, we asked whether LPS could induce GM-CSF production in MDA-MB-231 cells, and if so, which signaling pathway was involved. MDA-MB-231 cells were treated with LPS or tumor necrosis factor alpha (TNF-α; positive control), and GM-CSF expression levels were determined by qRT-PCR, ELISA, and confocal microscopy. Phosphorylation of the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-kB) signaling proteins were evaluated by flow cytometry. Our results show that LPS induces GM-CSF expression at both mRNA and protein levels in MDA-MBA-231 cells. Inhibition of acyl-CoA synthetase 1 (ACSL1) activity in the cells with triacsin C significantly reduces the secretion of GM-CSF. Furthermore, the inhibition of ACSL1 activity significantly blocks the LPS-mediated phosphorylation of p38 MAPK, MEK1/2, extracellular signal-regulated kinase (ERK)1/2, c-Jun NH2-terminal kinase (JNK), and nuclear factor-κB (NF-kB) in the cells. These findings provide the first evidence that LPS induces ACSL1-dependent GM-CSF gene expression in MDA-MB-231 breast cancer cells, which requires the activation of p38 MAPK, MEK1/2, ERK1/2, JNK, and NF-kB.
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Fujihara, Kazuya, Hiroaki Suzuki, Akira Sato, et al. "Circulating Malondialdehyde-Modified LDL-Related Variables and Coronary Artery Stenosis in Asymptomatic Patients with Type 2 Diabetes." Journal of Diabetes Research 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/507245.
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Aims. To elucidate the levels of malondialdehyde-modified LDL (MDA-LDL)-related variables for predicting coronary artery stenosis (CAS) by coronary CT angiography (CCTA) in asymptomatic patients with type 2 diabetes (T2DM).Methods. Enrolled were 36 Japanese patients with T2DM who underwent CCTA and in whom MDA-LDL levels were measured. Definition of CAS was luminal narrowing of ≥50%. Trends through tertiles of each MDA-LDL-related variable were analyzed with a general linear model. The ability of each MDA-LDL-related variable to predict CAS was compared to areas under the curve (AUCs) in receiver operating characteristic curve (ROC) analysis.Results. Seventeen patients had CAS. Each MDA-LDL-related variable was an independent predictor of CAS (P=0.039for MDALDL,P=0.013for MDA-LDL/LDL-C,P=0.047for MDA-LDL/HDL-C, andP=0.013for (MDA-LDL/LDL-C)/HDL-C). AUCs of MDA-LDL, MDA-LDL/LDL-C, MDA-LDL/HDL-C, and (MDA-LDL/LDL-C)/HDL-C were 0.675 (95% CI 0.496–0.854), 0.765 (0.602–0.927), 0.752 (0.592–0.913), and 0.799 (0.643–0.955), respectively, for predicting CAS. Trends throughout the tertiles showed significant associations between MDA-LDL/LDL-C, MDA-LDL/HDL-C, or (MDALDL/LDL-C)/HDL-C and CAS (P=0.003for MDA-LDL/LDL-C,P=0.042for MDA-LDL/HDL-C, andP=0.001for (MDA-LDL/LDL-C)/HDL-C).Conclusions. Data suggest that measurements of MDA-LDL/LDL-C, MDA-LDL/HDLC, and (MDA-LDL/LDL-C)/HDL-C are useful for predicting CAS.
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Yi, Jianing, Shuai Chen, Pingyong Yi, et al. "Pyrotinib Sensitizes 5-Fluorouracil-Resistant HER2+ Breast Cancer Cells to 5-Fluorouracil." Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 28, no. 5 (2020): 519–31. http://dx.doi.org/10.3727/096504020x15960154585410.
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5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for breast cancer. However, acquired chemoresistance leads to a loss of its efficacy; methods to reverse are urgently needed. Some studies have shown that pyrotinib, an ErbB receptor tyrosine kinase inhibitor, is effective against HER2+ breast cancer. However, whether pyrotinib sensitizes 5-FU-resistant breast cancer cells to 5-FU is unknown. We hypothesized that the combination of pyrotinib and 5-FU would show synergistic antitumor activity, and pyrotinib could reverse 5-FU resistance in HER2+ breast cancer cells in vitro and in vivo. Our data showed that pyrotinib inhibited the growth of 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines. 5-FU remarkably suppressed the growth of SKBR-3 and MAD-MB-453 cells. However, SKBR-3/FU and MAD-MB-453/FU cells showed resistance to 5-FU. A combination of pyrotinib and 5-FU resulted in the synergistic inhibition of the growth of the 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines. Pyrotinib decreased significantly the IC50 values of 5-FU and the thymidylate synthase (TS) mRNA expression levels in the 5-FU-resistant SKBR-3/FU and MDA-MB-453/FU cell lines and the parental cell lines and increased significantly the intracellular concentration of 5-FU in SKBR-3/FU and MDA-MB-453/FU cells. In addition, pyrotinib reduced the ABCG2 mRNA and protein expression levels in SKBR-3/FU and MDA-MB-453/FU cells and downregulated the protein expression levels of pAKT, pHER2, and pHER4 in all four cell lines. After TS or ABCG2 in 5-FU-resistant breast cancer cells was knocked down, the sensitivity of SKBR-3/FU and MDA-MB-453/FU cells to 5-FU was restored. Moreover, in vivo experiments demonstrated that pyrotinib in combination with 5-FU more effectively inhibited SKBR-3/FU tumor growth than either pyrotinib or 5-FU alone. In conclusion, our findings suggest that pyrotinib could restore sensitivity of 5-FU-resistant HER2+ breast cancer cells to 5-FU through downregulating the expression levels of TS and ABCG2.
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Cardenas-Garcia, Stivalis, Lucas Ferreri, Zhimin Wan, et al. "Maternally-Derived Antibodies Protect against Challenge with Highly Pathogenic Avian Influenza Virus of the H7N3 Subtype." Vaccines 7, no. 4 (2019): 163. http://dx.doi.org/10.3390/vaccines7040163.
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Vaccination of hens against influenza leads to the transfer of protective maternally-derived antibodies (MDA) to hatchlings. However, little is known about the transfer of H7N3 vaccine-induced MDA. Here, we evaluated transfer, duration, and protective effect of MDA in chickens against H7N3 HPAIV. To generate chickens with MDA (MDA (+)), 15-week-old White Leghorn hens were vaccinated and boosted twice with an inactivated H7N3 low pathogenic avian influenza virus vaccine, adjuvanted with Montanide ISA 71 VG. One week after the final boost, eggs were hatched. Eggs from non-vaccinated hens were hatched for chickens without MDA (MDA (−)). Both MDA (+) and MDA (−) hatchlings were monitored weekly for antibody levels. Anti-HA MDA were detected by hemagglutination inhibition assay mostly until day 7 post-hatch. However, anti-nucleoprotein MDA were still detected three weeks post-hatch. Three weeks post-hatch, chickens were challenged with 106 EID50/bird of Mexican-origin H7N3 HPAIV. Interestingly, while 0% of the MDA (−) chickens survived the challenge, 95% of the MDA (+) chickens survived. Furthermore, virus shedding was significantly reduced by day 5 post-challenge in the MDA (+) group. In conclusion, MDA confers partial protection against mortality upon challenge with H7N3 HPAIV, as far as three weeks post-hatch, even in the absence of detectable anti-HA antibodies, and reduce virus shedding after challenge.
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Abrahams, Beynon, Anthonie Gerber, and Donavon Charles Hiss. "Combination Treatment with EGFR Inhibitor and Doxorubicin Synergistically Inhibits Proliferation of MCF-7 Cells and MDA-MB-231 Triple-Negative Breast Cancer Cells In Vitro." International Journal of Molecular Sciences 25, no. 5 (2024): 3066. http://dx.doi.org/10.3390/ijms25053066.
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The role of the epidermal growth factor receptor (EGFR) in tumor progression and survival is often underplayed. Its expression and/or dysregulation is associated with disease advancement and poor patient outcome as well as drug resistance in breast cancer. EGFR is often overexpressed in breast cancer and particularly triple-negative breast cancer (TNBC), which currently lacks molecular targets. We examined the synergistic potential of an EGFR inhibitor (EGFRi) in combination with doxorubicin (Dox) in estrogen-positive (ER+) MCF-7 and MDA-MB-231 TNBC cell lines. The exposure of MDA-MB-231 and MCF-7 to EGFRi produced an IC50s of 6.03 µM and 3.96 µM, respectively. Dox induced MDA-MB-231 (IC50 9.67 µM) and MCF-7 (IC50 1.4 µM) cytotoxicity. Combinations of EGFRi-Dox significantly reduced the IC50 in MCF-7 (0.46 µM) and MBA-MB 231 (0.01 µM). Synergistic drug interactions in both cell lines were confirmed using the Bliss independence model. Pro-apoptotic Caspase-3/7 activation occurred in MCF-7 at 0.1–10 µM of EGFRi and Dox single treatments, whilst 1 μM Dox yielded a more potent effect on MDA-MB-231. EGFRi and Dox individually and in combination downregulated the EGFR gene expression in MCF-7 and MDA-MB-231 (p < 0.001). This study demonstrates EGFRi’s potential for eliciting synergistic interactions with Dox, causing enhanced growth inhibition, apoptosis induction, and downregulation of EGFR in both cell lines.
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Hassani, Fares Hassen. "The Relevance of Adiponectin and Resistin Levels with Oxidative Stress in Insulin Resistant Type 2 Diabetes." Kufa Journal for Nursing Sciences 5, no. 2 (2015): 47–52. http://dx.doi.org/10.36321/kjns.vi20152.2585.
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Objectives: The present study was designed to verify the changes of adiponectin and resistin with oxidativestress in insulin resistant in diabetes mellitus type 2. Methodology: To achieve this aim 60 patients with type 2 diabetes mellitus (24 male and 36 female ) of ages,53.9 ± 12.4 years in addition to 30 apparently healthy individuals (13 males and 17 females) were enrolled.The concentration of fasting blood glucose, triglyceride, insulin, adiponectin, resistin and malondialdehyde(MDA) levels were measured. Fasting insulin concentration, adiponectin and resistin was measured by enzymelinked immunosorbantassay( ELISA). Fasting blood glucose and triglyceride levels were determined byenzymatic methods. Malondialdehyde (MDA) levels were measured by spectrophotometeric methods . Insulinresistance was evaluated by four methods . Results: The results indicated that out of 60 patients, 49 (81%), 45 (75%), 33 (55%) and 32 (53%) wereinsulin resistant when they were evaluated by Homeostasis model assessment ( HOMA), Quantitative insulinsensitivity check index (QUICKI), McAuley's index (MCA) and fasting insulin(FI) indices respectively. The 49insulin resistant type 2 diabetic patients (IRP) that obtained through the HOMA method were assessed for thealteration in the levels adiponectin, resistin and MDA. The analysis of the data revealed a significant decrease ofadiponectin in the IRP group when compared with those of the insulin sensitive patients (ISP) and the controlgroups. Significant elevation of resistin levels were observed in the IRP group with respect to those of thecontrol groups. Conclusion: Insulin resistance was found to be significantly positively correlated with resistin, MDA andsignificantly negatively correlated with adiponectin levels in diabetic patients. Adiponectin exhibitedinsignificant negative correlation with resistin and significant negative correlation with MDA levels, while thelevel of resistin showed a significant positive correlation with MDA level in insulin resistant type 2 diabetics. Recommendations: A study on of the effect free fatty acid on the activity of insulin degrading enzymes in obeseindividual.
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Simpson, Kaitlyn E., Katrina L. Watson, and Roger A. Moorehead. "Elevated Expression of miR-200c/141 in MDA-MB-231 Cells Suppresses MXRA8 Levels and Impairs Breast Cancer Growth and Metastasis In Vivo." Genes 13, no. 4 (2022): 691. http://dx.doi.org/10.3390/genes13040691.
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Breast cancer cells with mesenchymal characteristics, particularly the claudin-low subtype, express extremely low levels of miR-200s. Therefore, this study examined the functional impact of restoring miR-200 expression in a human claudin-low breast cancer cell line MDA-MB-231. MDA-MB-231 cells were stably transfected with a control vector (MDA-231EV) or the miR-200c/141 cluster (MDA-231c141). Injection of MDA-231c141 cells into the 4th mammary gland of NCG mice produced tumors that developed significantly slower than tumors produced by MDA-231EV cells. Spontaneous metastasis to the lungs was also significantly reduced in MDA-231c141 cells compared to MDA-231EV cells. RNA sequencing of MDA-231EV and MDA-231c141 tumors identified genes including MXRA8 as being downregulated in the MDA-231c141 tumors. MXRA8 was further investigated as elevated levels of MXRA8 were associated with reduced distant metastasis free survival in breast cancer patients. Quantitative RT-PCR and Western blotting confirmed that MXRA8 expression was significantly higher in mammary tumors induced by MDA-231EV cells compared to those induced by MDA-231c141 cells. In addition, MXRA8 protein was present at high levels in metastatic tumor cells found in the lungs. This is the first study to implicate MXRA8 in human breast cancer, and our data suggests that miR-200s inhibit growth and metastasis of claudin-low mammary tumor cells in vivo through downregulating MXRA8 expression.
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Giachetti, Giovanni, Manuela Albert, Beatriz Marín, and Oscar Pastor. "Linking UML and MDD through UML Profiles: a Practical Approach based on the UML Association." JUCS - Journal of Universal Computer Science 16, no. (17) (2010): 2353–73. https://doi.org/10.3217/jucs-016-17-2353.
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In a model-driven development context, the definition (or selection) of an appropriate modeling language is a crucial task. OMG, in the model-driven architecture specification, recommends the use of UML for model-driven developments. However, the lack of semantic precision in UML has led to different model-driven approaches proposing their own domain-specific modeling languages in order to introduce their modeling needs. This paper focuses on customizing the UML association in order to facilitate its application in model-driven development environments. To do this, a well-defined process is defined to integrate the abstract syntax of a domain-specific modeling language that supports a precise semantics for the association construct in UML by means of the automatic generation of a UML profile. Finally, a brief example shows how the results obtained by the application of the proposed process can generate software products through a real model compilation tool.
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Singh, Sanjay, Maxime Munyeshyaka, Joy Gumin, et al. "TAMI-24. BEHAVIOR OF GLIOBLASTOMA STEM-LIKE CELLS WITH KNOWN IDH1 STATUS IN CEREBRAL ORGANOIDS." Neuro-Oncology 22, Supplement_2 (2020): ii218. http://dx.doi.org/10.1093/neuonc/noaa215.913.
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Abstract Glioblastomas (GBM) exhibit high proliferative index, areas of necrosis, high vascularization, and are highly invasive to normal brain tissues. The most common and lethal form of GBMs are primary GBMs, with no prior clinical history. Whereas, secondary GBMs arise from low-grade gliomas and are associated with IDH1 mutation. Pre-clinical studies of GBM largely depend on patient-derived GBM stem-like cells (GSCs) in vitro and in vivo as orthotopic xenografts. Cerebral organoids (COs) derived from induced pluripotent stem cells can serve as allogenic in vitro model systems to study interactions between normal brain and GSCs. COs have been shown to harbor neural stem cells and their differentiated progenies as well as microglia within distinct niches. Here, we co-cultured 45 day-old COs and MDA-GSCs lines representing mesenchymal sub-group (M-MDA-GSC), classical sub-group (C-MDA-GSC), and IDH1 mutant (IDH1R132H-MDA-GSC). MDA-GSCs stably express fluorescent proteins and is used to track GSCs within COs. These GSC bearing COs were fixed, embedded, sectioned, immuno-stained, and imaged by confocal microscope. There was a positive correlation between GSC numbers in allografted niche and invasion into COs as measured from the edge of organoid, M-MDA-GSC (R2=0.99; 0.89μm/cell), C-MDA-GSC (R2=0.92; 0.66μm/cell), and IDH1R132H-MDA-GSC (R2=0.89; 0.5μm/cell). Additionally, M-MDA-GSCs had significantly high percentage of Ki67+ve invasive cells (24%) in comparison to C-MDA-GSCs (5.1%; p=0.0057). As a measure of interaction of MDA-GSC with normal cells, we assessed proximity of IBA1+ve microglia in GSC niche within organoids and show that M-MDA-GSC and IDH1R132H-MDA-GSC highly co-localized with IBA1+ve microglia on day12 of co-culture. In conclusion, our cerebral organoid-based allograft study shows that mesenchymal GSCs (M-MDA-GSC) are most invasive whereas IDH1 mutant GSCs (IDH1R132H-MDA-GSC) are least invasive. C-MDA-GSCs are least proliferative while invading into normal COs. Uniqueness of CO based allograft system is highlighted by observed similarity between M-MDA-GSC and IDH1R132H-MDA-GSC for their potential to attract IBA1+ve microglia.
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Chew, E., J. Perin, T. Grader-Beck, and A. M. Orbai. "THU0611-HPR MEASUREMENT OF MINIMAL DISEASE ACTIVITY IN PSORIATIC ARTHRITIS USING PROMIS-PHYSICAL FUNCTION OR THE HEALTH ASSESSMENT QUESTIONNAIRE-DISABILITY INDEX." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 547.1–547. http://dx.doi.org/10.1136/annrheumdis-2020-eular.212.
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Background:Minimal disease activity (MDA) is a treat-to-target strategy (T2T) objective in psoriatic arthritis (PsA). MDA criteria, include physical function, traditionally assessed via the Health-Assessment Questionnaire Disability Index (HAQ-DI). It is of interest to assess the performance of more current physical function instruments such as the Patient-Reported Outcomes Measurement Information System-Physical Function Profile (PROMIS-PF).Objectives:To assess the interchangeability of the HAQ-DI with the PROMIS-PF in the calculation of MDA in PsA.Methods:Longitudinal PsA data were collected including HAQ-DI and PROMIS-PF in a PsA cohort. MDA definitions were built substituting the HAQ-DI criterion with the PROMIS-PF short form 4a (PROMIS-PF4a) or with the PROMIS-PF computer adaptive test (PROMIS-PF Bank). We assessed agreement/accuracy between HAQ-DI based and PROMIS-PF based MDA definitions at each visit and longitudinally through the kappa statistic/ROC curve analysis.Results:One hundred participants contributed 352 observations with up to five visits. Mean (SD) age was 52 (12) years, 60% were female, and 43% were in MDA at baseline. Kappa statistic for PROMIS-PF based MDA reflected almost perfect agreement with HAQ-DI MDA: kappa=0.94 (95% CI 0.90-0.97) for MDA PROMIS-PF Bank, and kappa=0.90 (95% CI 0.80-0.95) for MDA PROMIS-PF4a. Higher longitudinal agreement was seen between MDA HAQ-DI and MDA PROMIS-PF Bank versus MDA PROMIS-PF4a between consecutive visits: kappa ranged between 0.81-0.94 versus 0.72-0.84, respectively (Table 1). Area under ROC curve for predicting MDA HAQ-DI was 0.97 for MDA PROMIS-PF Bank and 0.95 for MDA PROMIS-PF4a (Figure 1).Table 1.Agreement between HAQ-DI based MDA and PROMIS-PF based MDA definitions at each visit and longitudinallyAgreementVisit 1Visit 2Visit 3Visit 4MDA HAQ-DI andMDA PROMIS-PF4aKappa95% CIN0.91(0.80-0.98)860.93(0.82-1.00)810.92(0.80-1.00)720.83(0.66-0.96)58MDA HAQ-DI andMDA PROMIS-PF4aKappa95% CIN0.91(0.81-0.98)860.98(0.90-1.00)820.94(0.84-1.00)730.93(0.82-1.00)58Longitudinal agreementVisit 1 to visit 2Visit 2 to visit 3Visit 3 to visit 4N/AMDA HAQ-DI state change withMDA PROMIS-PF4a state changeKappa95% CIN0.75(0.47-0.95)710.84(0.58-1.00)670.72(0.37-0.94)51N/AMDA HAQ-DI state change with MDA PROMIS-PF Bank state changeKappa95% CIN0.81(0.49-1.00)720.94(0.75-1.00)680.84(0.48-1.00)52N/A*Bias corrected 95% CI were calculated using bootstrapping with 2000 repetitions of individual patients.^MDA state changes are defined as transitions in the respective MDA state between designated consecutive visits.Abbreviations: CI confidence interval; N number of observations; HAQ-DI Heath Assessment Questionnaire-Disability Index; PROMIS-PF4a Patient Reported Outcomes Measurement Information System Physical Function form 4a; PROMIS-PF Bank Patient Reported Outcomes Measurement Information System Physical Function Bank administered as a computer adaptive test; MDA HAQ-DI Minimal disease activity includes the HAQ-DI ≤0.5 criterion; MDA PROMIS-PF4a includes the PROMIS-PF4a ≥41.3 criterion; MDA PROMIS-PF Bank includes the PROMIS-PF CAT ≥41.3 criterion.Figure 1.Areas under receiver operative characteristic curve to predict HAQ-DI based MDA using MDA PROMIS-PF4a or MDA PROMIS-PF Bank at each visit and overall using all observations (from left to right: visit 1, 2, 3, 4, and overall across visits)Conclusion:Excellent agreement was seen between HAQ-DI and PROMIS-based MDA definitions statically and longitudinally. The PROMIS-PF Bank and PROMIS-PF4a are accurate replacements for the HAQ-DI in calculating MDA state in PsA.References:[1]Schalet BD, et al. J Gen Intern Med 2015Disclosure of Interests:Erin Chew: None declared, Jamie Perin: None declared, Thomas Grader-Beck Grant/research support from: Abbvie, Celgene, Consultant of: Novartis, Lilly, Ana-Maria Orbai Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Consultant of: Eli Lilly; Janssen; Novartis; Pfizer; UCB. Ana-Maria Orbai was a private consultant or advisor for Sun Pharmaceutical Industries, Inc, not in her capacity as a Johns Hopkins faculty member and was not compensated for this service.
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Brown, D. J., E. J. Threlfall, M. D. Hampton, and B. Rowe. "Molecular characterization of plasmids in Salmonella enteritidis phage types." Epidemiology and Infection 110, no. 2 (1993): 209–16. http://dx.doi.org/10.1017/s0950268800068126.
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SUMMARYPlasmids in selected type strains of 26 of the Salmonella enteritidis phage types have been characterized by restriction enzyme fingerprinting and by DNA–DNA hybridization with oligonucleotide probes for Salmonella plasmid virulence (Spv) genes. With one exception, the fingerprints of the 38 MDa plasmids studied were homogeneous but there was heterogeneity in the fingerprints of 59 MDa plasmids found in 4 of the type strains. However all 38 MDa and 59 MDa plasmids were related as was a 45 MDa plasmid identified in the type strain of phage type 19. A 3·5 kb fragment homologous to SpvC was conserved in Hind III digests of all 38 MDa and 59 MDa plasmids, and in the related 45 MDa plasmid. In contrast a 65 MDa plasmid found in the type strain of phage type 10 was not related to these three plasmid molecular weight groups and did not carry the SpvC gene.
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Metcalfe, Lucy, Mathieu Chevalier, Marie-Pascale Tiberghien, et al. "Efficacy of a live intranasal vaccine against parainfluenza type 3 and bovine respiratory syncytial virus in young calves with maternally derived antibodies." Veterinary Record Open 7, no. 1 (2020): e000429. http://dx.doi.org/10.1136/vetreco-2020-000429.
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Trial designTwo randomised controlled vaccination trials with artificial challenges were carried out in addition to a serological survey of levels of maternally derived antibodies (MDA) to parainfluenza type 3 virus (PI3V) and bovine respiratory syncytial virus (BRSV) in European calves.ParticipantsTen-day-old calves with and without MDA were included in the two vaccine trials.InterventionsIntranasal administration of a bivalent modified live (PI3V/BRSV) vaccine followed by artificial challenge approximately three months post vaccination.ObjectiveThe study aimed to assess the efficacy of a modified live respiratory vaccine, Bovalto Respi Intranasal (Boehringer Ingelheim). In order to assess the interference of MDA, both seropositive and seronegative calves were used.RandomisationPI3V and BRSV serological status was determined seven days before vaccination; calves without maternal antibodies became the MDA− vaccinates. Calves with MDA were ranked according to individual titres and allocated alternately to MDA+ vaccinate and MDA+ control groups.BlindingTreatment was carried out by the unblinded study director. Animal care and veterinary examinations were conducted by personnel unaware of the treatments received. The serological survey used blood samples obtained from calves on commercial farms in five European countries, Germany, Spain, Italy, Ireland and the UK, to determine the levels of MDA to PI3V and BRSV in calves approximately two weeks of age.ResultsA total of 36 calves were included in the two challenge studies and 32 of these completed the challenge studies. Twenty-one calves were included in the PI3V challenge study, with six of six MDA− and six of seven MDA+ vaccinated calves and five of five MDA+ unvaccinated control calves being challenged with PI3V. Fifteen calves were included in the BRSV challenge study, with five of five MDA− and five of five MDA+ vaccinated calves and five of five MDA+ unvaccinated control calves being challenged with BRSV.OutcomeFor both challenges, clinical scores and nasal shedding were significantly higher in control animals compared with vaccinates (PI3V challenge: clinical scores P=0.001, nasal shedding P=0.001; BRSV challenge: clinical scores P=0.016, nasal shedding P=0.002) and not significantly different between MDA+ and MDA− vaccinated animals for both challenges (P>0.05). A total of 254 samples from six countries were tested in the serological survey of MDA.ConclusionThe results of the challenge studies demonstrated the efficacy of the vaccine in the presence of BRSV and PI3V MDA under laboratory conditions. The field assessment confirmed that the MDA titres in the MDA+ calves corresponded to those typically found on farms.
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Melzer, Catharina, Juliane von der Ohe, Tianjiao Luo, and Ralf Hass. "Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy." International Journal of Molecular Sciences 22, no. 11 (2021): 5930. http://dx.doi.org/10.3390/ijms22115930.
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Direct cellular interactions of MDA-MB-231cherry breast cancer cells with GFP-transduced human mesenchymal stroma/stem-like cells (MSCGFP) in a co-culture model resulted in spontaneous cell fusion by the generation of MDA-MSC-hyb5cherry GFP breast cancer hybrid cells. The proliferative capacity of MDA-MSC-hyb5 cells was enhanced about 1.8-fold when compared to the parental MDA-MB-231cherry breast cancer cells. In contrast to a spontaneous MDA-MB-231cherry induced tumor development in vivo within 18.8 days, the MDA-MSC-hyb5 cells initially remained quiescent in a dormancy-like state. At distinct time points after injection, NODscid mice started to develop MDA-MSC-hyb5 cell-induced tumors up to about a half year later. Following tumor initiation, however, tumor growth and formation of metastases in various different organs occurred rapidly within about 10.5 days. Changes in gene expression levels were evaluated by RNA-microarray analysis and revealed certain increase in dormancy-associated transcripts in MDA-MSC-hyb5. Chemotherapeutic responsiveness of MDA-MSC-hyb5 cells was partially enhanced when compared to MDA-MB-231 cells. However, some resistance, e.g., for taxol was detectable in cancer hybrid cells. Moreover, drug response partially changed during the tumor development of MDA-MSC-hyb5 cells; this suggests the presence of unstable in vivo phenotypes of MDA-hyb5 cells with increased tumor heterogeneity.
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Piñón-Zárate, Gabriela, Fernanda Reyes-Riquelme, Ma Beatriz Sánchez-Monroy та ін. "Immunomodulatory Properties of Masticadienonic Acid and 3α-Hydroxy Masticadienoic Acid in Dendritic Cells". Molecules 27, № 4 (2022): 1451. http://dx.doi.org/10.3390/molecules27041451.
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Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNFα or IFNγ. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3α-hydroxy masticadienoic acid (3α-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3α-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3α-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3α-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3α-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.
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Chen, Xiaosi, Zhifei He, Zefu Wang, and Hongjun Li. "Insight into the Interaction of Malondialdehyde with Rabbit Meat Myofibrillar Protein: Fluorescence Quenching and Protein Oxidation." Foods 12, no. 10 (2023): 2044. http://dx.doi.org/10.3390/foods12102044.
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This research explored the effects of oxidative modification caused by different malondialdehyde (MDA) concentrations on rabbit meat myofibrillar protein (MP) structural characteristics and the interactions between MDA and MP. The fluorescence intensity of MDA–MP adducts, and surface hydrophobicity increased, whereas the intrinsic fluorescence intensity and free-amine content of MPs decreased as MDA concentration and incubation time increased. The carbonyl content was 2.06 nmol/mg for native MPs, while the carbonyl contents increased to 5.17, 5.57, 7.01, 11.37, 13.78, and 23.24 nmol/mg for MP treated with 0.25 to 8 mM MDA, respectively. When the MP was treated with 0.25 mM MDA, the sulfhydryl content and the α-helix content decreased to 43.78 nmol/mg and 38.46%, while when MDA concentration increased to 8 mM, the contents for sulfhydryl and α-helix decreased to 25.70 nmol/mg and 15.32%. Furthermore, the denaturation temperature and ΔH decreased with the increase in MDA concentration, and the peaks disappeared when the MDA concentration reached 8 mM. Those results indicate MDA modification resulted in structural destruction, thermal stability reduction, and protein aggregation. Besides, the first-order kinetics and Stern–Volmer equation fitting results imply that the quenching mechanism of MP by MDA may be mainly driven by dynamic quenching.
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Goward, Dana A. "MDA—Crummy Name, Great Idea." Marine Technology Society Journal 45, no. 3 (2011): 10–11. http://dx.doi.org/10.4031/mtsj.45.3.9.
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Kravchenko, Yuri, Ilona Kursitys, and Victoria Bova. "Knowledge sifters in MDA technologies." Journal of Physics: Conference Series 1015 (May 2018): 042024. http://dx.doi.org/10.1088/1742-6596/1015/4/042024.
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Stump, Elizabeth. "MDA CEO ROBERT ROSS DIES." Neurology Today 6, no. 14 (2006): 3. http://dx.doi.org/10.1097/00132985-200607180-00002.
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Holloway, Myles. "AN INTERVIEW WITH ZAKES MDA." South African Theatre Journal 2, no. 2 (1988): 81–88. http://dx.doi.org/10.1080/10137548.1988.9687619.
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Lumertz, Paulo, Ana Paula Terra Bacelo, and Toacy Oliveira. "Quantools: A MDA transformation approach." Revista de Informática Teórica e Aplicada 16, no. 2 (2010): 53–56. http://dx.doi.org/10.22456/2175-2745.12509.
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Model driven architecture (MDA) represents a challenge for the companies to increase the benefits of code generation, creating systems by using common libraries and standards. This paper presents the Quantools that is a result of a 5-year project, introducing the benefits of MDA in a Brazilian software development company. Quantools is based on the concept of cartridges that specify the transformation rules and constraints for a particular domain. The tool may be integrated to the modeling activities of the system to check the correctness of models according to the standards previously defined. The Quantools and its Cartridges execute transformations to generate the source code in a particular domain.
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Mda, Zakes, and Elly Williams. "An Interview with Zakes Mda." Missouri Review 28, no. 2 (2005): 62–79. http://dx.doi.org/10.1353/mis.2006.0034.
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Bouma, Suzanne, Lieke van Lieshout-Beenker, Iris Andriessen, and Janine Janssen. "Een kritische blik op MDA++." PROCES 104, no. 2 (2025): 111–24. https://doi.org/10.5553/proces/016500762025104002005.
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Why collaboration in tackling complex forms of domestic violence is so difficult In the Netherlands, a special form of collaboration in dealing with domestic violence and the abuse of children. is the so-called MDA++ approach. MDA++ is characterized as a solution to the bottlenecks in the regular approach of these violent phenomena. The letters MDA stand for Multidisciplinary Approach. The first plus sign stands for ‘intersectoral and multidisciplinary’ and implies cooperation in and between the aid chain, safety chain and the medical care circuit. The second plus sign stands for ‘specialist’, which means that all professionals are experts in their own field and have knowledge about the effect of violence, neglect and abuse on individuals and relationships. In this contribution based on a review of literature an overview is given of the genesis of MDA++ and successes and problems of its implementation in practice.