Pipeline life extension and integrity management based on optimized use of above ground survey data and inline inspection results

We present a detailed description of probabilistic methodologies based on Bayesian updating and structural reliability analysis for optimizing sur­vey and/or inspection frequencies in a way that provides cost-effective solutions for ongoing integrity management or indeed for life extension or pressure uprating. A full description of the method is provided and the application of the techniques is clearly illustrated through case studies.Детально описано ймовірнісні методики, що базуються на обновленні даних за Байесом і розрахунку надійності конструкцій. Методики використову­ ються для оптимізації діагностичного огляду і (або) частоти проведення локальних інспекцій трубопроводів. Це гарантує економічний розв’язок проблем забезпечення працездатності трубопроводів, подовження їх довго­вічності чи оптимізації тиску в них. Суть запропонованої методики й особли­вості її використання описано на різних прикладах.Подробно описаны вероятностные методики, основанные на обновлении данных по Байесу и расчете надежности конструкций. Методики используются для оптимизации диагностичес­ких осмотров и (или) частоты проведения локальних инспекций трубопроводов. Это гаранти­рует экономичное решение проблем обеспечения работоспособности трубопроводов, про­дления их долговечности или оптимизации давления в них. Суть предложенной методики и особенности ее применения детально описаны на различных примерах

Enterohemorrhagic Escherichia coli O157∶H7 Gene Expression Profiling in Response to Growth in the Presence of Host Epithelia

BACKGROUND: The pathogenesis of enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection is attributed to virulence factors encoded on multiple pathogenicity islands. Previous studies have shown that EHEC O157:H7 modulates host cell signal transduction cascades, independent of toxins and rearrangement of the cytoskeleton. However, the virulence factors and mechanisms responsible for EHEC-mediated subversion of signal transduction remain to be determined. Therefore, the purpose of this study was to first identify differentially regulated genes in response to EHEC O157:H7 grown in the presence of epithelial cells, compared to growth in the absence of epithelial cells (that is, growth in minimal essential tissue culture medium alone, minimal essential tissue culture medium in the presence of 5% CO(2), and Penassay broth alone) and, second, to identify EHEC virulence factors responsible for pathogen modulation of host cell signal transduction. METHODOLOGY/PRINCIPAL FINDINGS: Overnight cultures of EHEC O157:H7 were incubated for 6 hr at 37 degrees C in the presence or absence of confluent epithelial (HEp-2) cells. Total RNA was then extracted and used for microarray analyses (Affymetrix E. coli Genome 2.0 gene chips). Relative to bacteria grown in each of the other conditions, EHEC O157:H7 cultured in the presence of cultured epithelial cells displayed a distinct gene-expression profile. A 2.0-fold increase in the expression of 71 genes and a 2.0-fold decrease in expression of 60 other genes were identified in EHEC O157:H7 grown in the presence of epithelial cells, compared to bacteria grown in media alone. CONCLUSION/SIGNIFICANCE: Microarray analyses and gene deletion identified a protease on O-island 50, gene Z1787, as a potential virulence factor responsible for mediating EHEC inhibition of the interferon (IFN)-gamma-Jak1,2-STAT-1 signal transduction cascade. Up-regulated genes provide novel targets for use in developing strategies to interrupt the infectious process

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

Does Consideration and Assessment of Effects on Health Equity Affect the Conclusions of Systematic Reviews? A Methodology Study

INTRODUCTION: Tackling health inequities both within and between countries remains high on the agenda of international organizations including the World Health Organization and local, regional and national governments. Systematic reviews can be a useful tool to assess effects on equity in health status because they include studies conducted in a variety of settings and populations. This study aims to describe the extent to which the impacts of health interventions on equity in health status are considered in systematic reviews, describe methods used, and assess the implications of their equity related findings for policy, practice and research. METHODS: We conducted a methodology study of equity assessment in systematic reviews. Two independent reviewers extracted information on the reporting and analysis of impacts of health interventions on equity in health status in a group of 300 systematic reviews collected from all systematic reviews indexed in one month of MEDLINE, using a pre-tested data collection form. Any differences in data extraction were resolved by discussion. RESULTS: Of the 300 systematic reviews, 224 assessed the effectiveness of interventions on health outcomes. Of these 224 reviews, 29 systematic reviews assessed effects on equity in health status using subgroup analysis or targeted analyses of vulnerable populations. Of these, seven conducted subgroup analyses related to health equity which were reported in insufficient detail to judge their credibility. Of these 29 reviews, 18 described implications for policy and practice based on assessment of effects on health equity. CONCLUSION: The quality and completeness of reporting should be enhanced as a priority, because without this policymakers and practitioners will continue lack the evidence base they need to inform decision-making about health inequity. Furthermore, there is a need to develop methods to systematically consider impacts on equity in health status that is currently lacking in systematic reviews

Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue.</p> <p>Methods</p> <p>H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer.</p> <p>Results</p> <p>H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth.</p> <p>Conclusion</p> <p>These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.</p

Identifying Mechanisms by Which Escherichia coli O157:H7 Subverts Interferon-γ Mediated Signal Transducer and Activator of Transcription-1 Activation

Enterohemorrhagic Escherichia coli serotype O157:H7 is a food borne enteric bacterial pathogen that causes significant morbidity and mortality in both developing and industrialized nations. E. coli O157:H7 infection of host epithelial cells inhibits the interferon gamma pro-inflammatory signaling pathway, which is important for host defense against microbial pathogens, through the inhibition of Stat-1 tyrosine phosphorylation. The aim of this study was to determine which bacterial factors are involved in the inhibition of Stat-1 tyrosine phosphorylation. Human epithelial cells were challenged with either live bacteria or bacterial-derived culture supernatants, stimulated with interferon-gamma, and epithelial cell protein extracts were then analyzed by immunoblotting. The results show that Stat-1 tyrosine phosphorylation was inhibited by E. coli O157:H7 secreted proteins. Using sequential anion exchange and size exclusion chromatography, YodA was identified, but not confirmed to mediate subversion of the Stat-1 signaling pathway using isogenic mutants. We conclude that E. coli O157:H7 subverts Stat-1 tyrosine phosphorylation in response to interferon-gamma through a still as yet unidentified secreted bacterial protein

PENGARUH ANGKUTAN UMUM ONLINE TERHADAP ANGKUTAN UMUM KONVENSIONAL (STUDI KASUS ANGKUTAN ADL DAN MAXIM DI KOTA MALANG)

Munculnya transportasi berbasis online menimbulkan aksi demonstrasi besar diwilayah jawa timur salah satunya dikota Malang,aksi dilakukan oleh para pengemudi angkutan konvensional untuk menentang beroprasinya bisnis transportasi online di Indonesia khususnya dikota Malang.mereka beralasan bahwa hadirnya moda transportasi online dapat mematikan mata pencaharian dan mengurangi penghasilan mereka secara drastis.Untuk mengetahui pengaruh adanya transportasi online terhadap transportasi konvensional maka diadakan penelitian untuk menegtahui kinerja angkutan umum online dan angkutan umum konvensional pada trayek ADL (Arjosari-Dinoyo Landungsari),dengan menggunakan metode Custumer Statisfaction Index (CSI).setelah dilakukan peneltian maka peneliti mendapatkan hasil analisis bahwa pengaruh transportasi online terhadap transportasi konvensional di Kota Malang berdasarkan pada kulitas pelayanan.Dari hasi analisis data menggunakan metode CSI bahawa kepuasan penumpang terhadap kualitas pelayananan angkutan online sebesar 82,22% dengan kategori “puas”dan kepuasan penumpang terhadap kualitas pelayanan angkutan Konvensional sebesar 58.17% dengan kategori “Cukup Puas”.Sehingga dapat disimpulkan bahwa pengaruh angkutan online terhadap angkutan konvensional terdapat pada kulitas pelayanan dari kedua angkutan tersebut.Agar angkutan konvensional bisa memikat kembali daya tarik pengguna angkutan konvensional maka peneliti menawarkan solusi. Sesuai dengan hasil analisis data&nbsp; bahwa penumpang merasa kurang nyaman saat berada diangkutan konvensional yakni salah satunya adalah &nbsp;untuk angkutan konvesnional harus membawa penumpang sesuai kapasitas yang diijinkan dan mengurangi kepadatan agar penumpang tidak terasa sesak sehingga membuat penumpang merasa tidak nyaman,peneliti juga Mengambil langkah-langkah lain seperti tindakan kebersihan yang terlihat dan mengenakan masker apa lagi sekarang dalam masa pandemi dan juga dapat membantu meyakinkan penumpang, Solusi yang kedua adalah kebersihan kendaraan dan fasiltas kendaraan yang layak dipakai seperti contoh kendaraan yang tempat duduknya kurang layak dipakai/rusak,sehingga para pengguna angkutan konvensional merasa nyaman dengan tempat duduknya.Dari solusi yang ditawarkan tujuanya adalah angkutan konvensional punya daya Tarik tersendiri sehingga para pengguna jasa angkutan konvensional mempunyai daya tarik tersendiri sehingga membuatnya untuk kembali menggunakan angkutan konvensiona

PENGARUH ANGKUTAN UMUM ONLINE TERHADAP ANGKUTAN UMUM KONVENSIONAL (STUDI KASUS ANGKUTAN ADL DAN MAXIM DI KOTA MALANG)

Munculnya transportasi berbasis online menimbulkan aksi demonstrasi besar diwilayah jawa timur salah satunya dikota Malang,aksi dilakukan oleh para pengemudi angkutan konvensional untuk menentang beroprasinya bisnis transportasi online di Indonesia khususnya dikota Malang.mereka beralasan bahwa hadirnya moda transportasi online dapat mematikan mata pencaharian dan mengurangi penghasilan mereka secara drastis.Untuk mengetahui pengaruh adanya transportasi online terhadap transportasi konvensional maka diadakan penelitian untuk menegtahui kinerja angkutan umum online dan angkutan umum konvensional pada trayek ADL (Arjosari-Dinoyo Landungsari),dengan menggunakan metode Custumer Statisfaction Index (CSI).setelah dilakukan peneltian maka peneliti mendapatkan hasil analisis bahwa pengaruh transportasi online terhadap transportasi konvensional di Kota Malang berdasarkan pada kulitas pelayanan.Dari hasi analisis data menggunakan metode CSI bahawa kepuasan penumpang terhadap kualitas pelayananan angkutan online sebesar 82,22% dengan kategori “puas”dan kepuasan penumpang terhadap kualitas pelayanan angkutan Konvensional sebesar 58.17% dengan kategori “Cukup Puas”.Sehingga dapat disimpulkan bahwa pengaruh angkutan online terhadap angkutan konvensional terdapat pada kulitas pelayanan dari kedua angkutan tersebut.Agar angkutan konvensional bisa memikat kembali daya tarik pengguna angkutan konvensional maka peneliti menawarkan solusi. Sesuai dengan hasil analisis data  bahwa penumpang merasa kurang nyaman saat berada diangkutan konvensional yakni salah satunya adalah  untuk angkutan konvesnional harus membawa penumpang sesuai kapasitas yang diijinkan dan mengurangi kepadatan agar penumpang tidak terasa sesak sehingga membuat penumpang merasa tidak nyaman,peneliti juga Mengambil langkah-langkah lain seperti tindakan kebersihan yang terlihat dan mengenakan masker apa lagi sekarang dalam masa pandemi dan juga dapat membantu meyakinkan penumpang,(Sulistyawati dan Dewi 2021),Solusi yang kedua adalah kebersihan kendaraan dan fasiltas kendaraan yang layak dipakai seperti contoh kendaraan yang tempat duduknya kurang layak dipakai/rusak,sehingga para pengguna angkutan konvensional merasa nyaman dengan tempat duduknya.Dari solusi yang ditawarkan tujuanya adalah angkutan konvensional punya daya Tarik tersendiri sehingga para pengguna jasa angkutan konvensional mempunyai daya tarik tersendiri sehingga membuatnya untuk kembali menggunakan angkutan konvensional