9 results on '"Amos Simon"'
Search Results
2. Author Correction: Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells
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Marcin Łyszkiewicz, Natalia Ziętara, Laura Frey, Ulrich Pannicke, Marcel Stern, Yanshan Liu, Yanxin Fan, Jacek Puchałka, Sebastian Hollizeck, Ido Somekh, Meino Rohlfs, Tuğba Yilmaz, Ekrem Ünal, Musa Karakukcu, Türkan Patiroğlu, Christina Kellerer, Ebru Karasu, Karl-Walter Sykora, Atar Lev, Amos Simon, Raz Somech, Joachim Roesler, Manfred Hoenig, Oliver T. Keppler, Klaus Schwarz, and Christoph Klein
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Science - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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3. The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets†
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Naomi Pode‐Shakked, Rachel Shukrun, Michal Mark‐Danieli, Peter Tsvetkov, Sarit Bahar, Sara Pri‐Chen, Ronald S. Goldstein, Eithan Rom‐Gross, Yoram Mor, Edward Fridman, Karen Meir, Amos Simon, Marcus Magister, Naftali Kaminski, Victor S. Goldmacher, Orit Harari‐Steinberg, and Benjamin Dekel
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cancer initiating cells ,cancer stem cells ,kidney stem cells ,renal progenitor cells ,targeted therapy ,Medicine (General) ,R5-920 ,Genetics ,QH426-470 - Abstract
Abstract There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated – NCAM1 expressing – “blastema” phenotype, including a capacity to expand and differentiate into the mature renal‐like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR‐200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets. →See accompanying article http://dx.doi.org/10.1002/emmm.201202173
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- 2012
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4. Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling
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Danny Ben‐Zvi, Naphtali Savion, Frank Kolodgie, Amos Simon, Sudeshna Fisch, Katrin Schäfer, Noa Bachner‐Hinenzon, Xin Cao, Arieh Gertler, Gili Solomon, Erez Kachel, Ehud Raanani, Jacob Lavee, Shlomo Kotev Emeth, Renu Virmani, Frederick J. Schoen, and Jacob Schneiderman
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angiotensin II ,aortic aneurysm ,aortic valve stenosis ,left ventricular hypertrophy ,leptin ,leptin antagonist ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundAscending thoracic aortic aneurysm (ATAA) is driven by angiotensin II (AngII) and contributes to the development of left ventricular (LV) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments AngII‐induced abdominal aortic aneurysms in apolipoprotein E–deficient mice. We hypothesized that locally synthesized leptin mediates AngII‐induced ATAA. Methods and ResultsFollowing demonstration of leptin synthesis in samples of human ATAA associated with different etiologies, we modeled in situ leptin expression in apolipoprotein E–deficient mice by applying exogenous leptin on the surface of the ascending aorta. This treatment resulted in local aortic stiffening and dilation, LV hypertrophy, and thickening of aortic/mitral valve leaflets. Similar results were obtained in an AngII‐infusion ATAA mouse model. To test the dependence of AngII‐induced aortic and LV remodeling on leptin activity, a leptin antagonist was applied to the ascending aorta in AngII‐infused mice. Locally applied single low‐dose leptin antagonist moderated AngII‐induced ascending aortic dilation and protected mice from ATAA rupture. Furthermore, LV hypertrophy was attenuated and thickening of aortic valve leaflets was moderated. Last, analysis of human aortic valve stenosis leaflets revealed de novo leptin synthesis, whereas exogenous leptin stimulated proliferation and promoted mineralization of human valve interstitial cells in culture. ConclusionsAngII‐induced ATAA is mediated by locally synthesized leptin. Aortoventricular hemodynamic coupling drives LV hypertrophy and promotes early aortic valve lesions, possibly mediated by valvular in situ leptin synthesis. Clinical implementation of local leptin antagonist therapy may attenuate AngII‐induced ATAA and moderate related LV hypertrophy and pre–aortic valve stenosis lesions. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT00449306.
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- 2016
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5. Numerical analysis and material selection of functionally graded pipes based on metals and ceramics for deep offshore oil and gas operations in Gulf of Guinea
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Amos, Simon Olushola and Nash, David
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665.5 - Abstract
The environmentally challenged conditions of deep offshore oil and gas operations has necessitated the demand for unique materials that could withstand both the loading conditions of the operations and the corrosion resistance. The work presented herein has explored the use of Functionally Graded Material (FGM) to validate its ability to proffer solutions to deep offshore oil and gas operations and their components, particularly in the Gulf of Guinea. FGM was specifically used in the present work due to its unique property exhibition that changes continuously throughout its thickness with no discontinuities within the material. This unique feature was utilized in this research to derive a combination of FGM's that could meet the required strength, fracture toughness, specific stiffness and corrosion rate for oil and gas operations in Gulf of Guinea. An assessment of currently available material combinations was investigated to determine feasible FGM combinations (metal and ceramics) that could meet the unique operating requirements. In tandem, the Analytic Hierarchy Process (AHP) technique was further used to rank the materials identified and a sensitivity analysis was carried out on weight, price and density variations in the final ranking the material. The four (4) most highly ranked Metal/Ceramic combinations were used for all the finite element thermal and structural analyses undertaken in this work. Four (4) distinct FGM pipe were modelled by finite element analysis (FEA) using the Abaqus Finite Element system based on the key Metal/Ceramics materials selected, to reasonably mimic the physical behaviour of a series of offshore piping systems configurations. In practice, three piping configurations were considered; Straight, Elbow and T- Piece pipe components, all these were modelled for a range of pressure and temperature conditions. From the reviewed literature, only a few benchmarks were available to validate the computational models, this is as a result of the evolving nature of the usage of FGM for piping in oil and gas industry. Using work by Ghannad et al. on '2D thermo-elastic model of an axisymmetric FGM hollow cylinder', the FGM parameters used for the validation were axial stress, circumferential stress and von-mises stress. The comparison of results obtained from Ghannad's Paper showed excellent agreement with deviations of most of the variables used for the within 5% with both the numerical and analytical results from the literature. As an FGM cannot have a single yield point by definition, an equation for the determination of effective yield strength for FGM's was developed which depends on the yield strength of the FGM constituents and the non-homogeneity factor of the FGM. This equation was validated using the conventional averaging approach of the FGM yield strengths and it showed excellent agreement with less than 1% for FGM's with higher numbers of layers. Further to the determination of an ideal approach to calculate the effective yield strength of the FGM's, the Finite Element Analysis (FEA) of the four FGM combinations were modelled using the approach in the validated model with the main intent of predicting the design limits for each of the FGM material combinations. This was repeated for the three piping components considered (Straight, Elbow and T-Piece Pipe configurations). The normalized stress approach was used for the determination of the design limit, this approach compared the effective yield strength of the FGM to the effective Von-mises stress for each of the configurations to determine the FGM failure tendencies due to yielding. The FGM design limit was determined when any of the layer in the FGM normalized stress was closest to one (1), above this limit the material begins to yield (Fail). The design limit was determined using the normalized stress between the ranges of 0.99 < normalized stress < 1.01. The FEA of the FGM's considered was limited to thermal and pressure loading, hence only thermal and pressure design limits were determined for all the FG's considered in all the configurations and non-homogeneity factors. From the typical oil and gas operating conditions considered in Gulf of Guinea, the design limit results for the Straight pipes reveals that all the 20 FGM's could be deployed for the operations being considered. The results from this study allowed straight FGM's to be ranked based on thermal and pressure loading conditions. On the same note, the design limit results for the Elbow Pipes reveals that only 10 FG's from the 20 modelled FG's could be adequately deployed for the operations being considered. The results from this study allowed elbow FGM's to be ranked based on thermal and pressure loading conditions. Furthermore, the design limit results for the T-Pieces Pipes reveals that all the FGM's modelled could be adequately deployed for the operations being considered. The results from this study allowed T-piece FGM's to be ranked based on thermal and pressure loading conditions. Finally, it is worth noting that the work undertaken herein concludes the development of a matrix of internal pressure and thermal loading for Straight, Elbow and T-Piece FGM Pipe configurations that could serve as guide for FGM material selection for oil and gas service conditions similar to that in Gulf of Guinea.
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- 2020
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6. Effective Asset/Portfolio Management: NAPIMS Perspective
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Nnakenyi, Norbert, additional, Amos, Simon Olushola, additional, Abegunde, Mobolaji, additional, Ayo-Dayisi, Ibidunni, additional, Anozie, Nnabuike, additional, Gari, Tayiro, additional, Akintade, Olusemola, additional, Musa, Aminu, additional, and Ibrahim, Habeeb, additional
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- 2022
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7. Inadequate Activation of γδT- and B-cells in Patient with Wiskott-Aldrich Syndrome (WAS) Portrayed by TRG and IGH Repertoire Analyses
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Dahlia Palevski, Amos Simon, Atar Lev, Raz Somech, and Yu Nee Lee
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Immunology ,Immunology and Allergy - Abstract
Patients with Wiskott-Aldrich syndrome (WAS) harbor mutations in the WAS gene and suffer from immunodeficiency, microthrombocytopenia, and eczema. T-cells play an important role in immune response in the skin and the γδT-cells have an important role in skin homeostasis. Since WAS patients often present with eczema, we wanted to examine whether the T-cell receptor gamma (TRG) repertoire of the γδT-cells is affected in these patients. In addition, the immunoglobulin heavy chain (IGH) repertoire from genomic DNA of WAS patients was not yet studied. Thus, we sought to determine the effects that specific WAS mutations from our patients have in shaping the TRG and IGH immune repertoires. We collected clinical and genetic data on four WAS patients, each harboring a different mutation in the WAS gene. Using next-generation sequencing (NGS), we analyzed their TRG and IGH repertoires using genomic DNA isolated from their peripheral blood. We analyzed the TRG and IGH repertoire sequences to show repertoire restriction, clonal expansions, preferential utilization of specific V genes, and unique characteristics of the antigen binding region in WAS patients with eczema compared to healthy controls. Both the TRG and IGH repertoire showed diverse repertoire comparable to healthy controls on one the hand, and on the other hand, the IGH repertoire showed increased diversity, more evenly distributed repertoire and immaturity of the antigen binding region. Thus, we demonstrate by analyzing the repertoire based on genomic DNA, the various effect that WAS mutations have in shaping the TRG and IGH adaptive immune repertoires.
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- 2022
8. Novel XLF/Cernunnos mutation linked to severe combined immunodeficiency, microcephaly and abnormal T and B cell receptor repertoires
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Shirly Frizinsky, Erez Rechavi, Ortal Barel, Yu-Nee Lee, Amos Simon, Atar Lev, Tali Stauber, and Raz Somech
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Background: During the process of generating diverse T and B cell receptor (TCR and BCR, respectively) repertoires, double strand DNA breaks are produced. Subsequently, these breaks are corrected by a complexed system led mainly by the non-homologous end-joining (NHEJ). Mutations in proteins involved in this process, including the XLF/ Cernunnos gene, cause severe combined immunodeficiency syndrome (SCID) along with neurodevelopmental disease and susseptability to inoizing radiation. Objective: To provide new clinical and immunological insights on XLF/Cernunnos deficiency, arising from a newly diagnosed patient with severe immunodeficiency. Methods: A male infant, born to consanguineous parents, suspected of having primary immunodeficiency underwent immunological and genetic work up. This included a thorough assessment of T cell phenotyping and lymphocyte activation by mitogen stimulation tests, whole exome sequencing (WES), TCR repertoire Vβ repertoire via flow cytometry analysis and TCR and BCR via next generation sequencing (NGS). Results: Clinical findings included microcephaly, recurrent bacterial viral pneumonia and failure to thrive. Immune workup revealed lymphopenia, reduced T cell function and hypogammaglubolinemia. A skewed TCR Vβ repertoire, TCR gamma (TRG) repertoire and BCR repertoire were determined in the patient. Genetic analysis identified a novel autosomal recessive homozygous missense mutation in XLF/Cernunnos c. A580Ins.T; p. M194fs. The patient underwent a successful hematopoietic stem cell transplantation (HSCT). Conclusions: A novel XLF/Cernunnos mutation is reported in a patient presented with SCID phenotype that displayed clonally expanded T and B cells. An adjusted HSCT was safe to ensure full T cell immune reconstitution.
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- 2021
9. Numerical analysis and material selection of functionally graded pipes based on metals and ceramics for deep offshore oil and gas operations in Gulf of Guinea
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Amos, Simon Olushola.
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- 2020
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