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Altered energy metabolism and metabolic gene expression associated with increased metastatic capacity identified in MDA -MB-231 cell line variants

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 678-693页

作者： Yan Tu Cameron N.Johnstone James g.Ryall guillermo H.Lopez-Campos Christine R.Keenan alastair g.stewart Department of Pharmacology and Therapeutics the University of MelbourneParkvilleVictoria 3010Australia Cancer Research Division Peter MacCallum Cancer CentreEast MelbourneVictoria 3000Australia Olivia Newton-John Cancer Research Institute HeidelbergVictoria 3084Australia School of Cancer Medicine La Trobe UniversityBundooraVictoria 3086Australia Department of Biochemistry&Molecular Biology Monash UniversityClaytonVictoria 3800Australia Department of Pathology the University of MelbourneParkvilleVictoria 3010Australia Department of Physiology the University of MelbourneParkvilleVictoria 3010Australia Health and Biomedical Informatics Centre Melbourne Medical Schoolthe University of MelbourneVictoria 3010Australia The Wellcome-Wolfson Institute for Experimental Medicine Queen's UniversityBelfast BT97BLUK The Walter and Eliza Hall Institute of Medical Research ParkvilleVictoria 3010Australia Department of Medical Biology The University of MelbourneParkvilleVictoria 3010Australia

Aim:Despite current advances in therapies and the gradual decline in breast cancer-related mortality,metastasis remains a major therapeutic challenge for *** reprogramming is now recognized to be an important part of tumorigenic processes,but its relevance in metastatic dissemination has yet to be ***:Using the ***5 cell line,a novel,highly metastatic variant line derived from TN hu-man breast adenocarcinoma MDA-MB-231 line,alteration in growth and energy metabolisms associated with en-hanced metastatic potential were *** and oxidative phosphorylation(OXPHOS)was character-ized using the seahorse XF *** transcriptome sequencing(RNA-seq)and quantitative real-time PCR was used to ascertain expression differences in metabolic ***:We observed reduced proliferation,and an elevation of both glycolytic and OXPHOS metabolism in the highly metastatic daughter *** elevated metabolic rate is only partially reflected by transcript levels of rel-evant metabolic *** mitochondrial respiration is potentially underpinned by increased expres-sion mitochondrial electron transport chain ***,increased glycolysis was not underpinned by up-regulation of metabolic genes encoding enzymes participating in ***:Our results indicate breast tumour cells with elevated metastatic propensity are more metabolic *** also identified differentially expressed metabolic genes,such as IDH2,that may play a part in the meta-static process beyond energy reprogramming.

关键词： Breast cancer energy reprogramming cancer metabolism metastasis RNA-seq

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Arbitrary Lagrangian–Eulerian simulations of highly electrically charged micro-droplet Coulomb explosion deformation pathways

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International Journal of Modeling, Simulation, and Scientific Computing 2016年第3期7卷 136-149页

作者： alastair Radcliffe CIMAP unit´e mixte CEA-CNRS-ENSICAEN-UCBN 6252 BP 5133F-14070 CaenCedex 05France University of Warwick Coventry CV47ALUK.

Numerical simulation results of the Coulomb explosion pathways of cooled water and heated glycol droplets electrically charged to the critical Rayleigh limit are presented,calculated using an axi-symmetric finite element scheme previously used for the same problem[Radcliffe A.J.,Non-conforming finite elements for axisymmetric charged droplet deformation dynamics and Coulomb explosions,*** 71:249–268,(2013),doi:10.1002/fld.3667.]which has been adapted to use arbitrary Lagrangian–Eulerian(ALE)methods and a novel tip reconstruction technique in order to greatly improve its accuracy in matching available experimental data.

关键词： Electrohydrodynamics finite elements droplet deformations.

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In search of a roadmap towards improving care of patients with cirrhosis and ascites, could a platform trial design transform clinical research?

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Hepatobiliary Surgery and Nutrition 2022年第6期11卷 889-892页

作者： alastair O’Brien University College London(UCL)Institute for Liver and Digestive Health Division of MedicineRoyal Free CampusLondonUK

The authors of“Diagnosis,Evaluation,and Management of Ascites,Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome:2021 Practice guidance by the American Association for the Study of Liver Diseases”are to be congratulated on their exhaustive assessment of the data published on patients with cirrhosis and ascites and their guidelines represent a pragmatic,evidence-based,common-sense approach(1).

关键词： patients ascites cirrhosis

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Interaction of Waves, Surface Currents, and Turbulence: the Application of Surface-Following Coordinate Systems

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Journal of Ocean University of China 2007年第4期6卷 319-331页

作者： Jenkins alastair D Bjerknes Centre for Climate Research Geophysical Institute Allegaten 70 N-5007 Bergen Norway

Surface waves comprise an important aspect of the interaction between the atmosphere and the ocean, so a dynamically consistent framework for modelling atmosphere-ocean interaction must take account of surface waves, either implicitly or explicitly. In order to calculate the effect of wind forcing on waves and currents, and vice versa, it is necessary to employ a consistent formula- tion of the energy and momentum balance within the airflow, wave field, and water column. It is very advantageous to apply sur- face-following coordinate systems, whereby the steep gradients in mean flow properties near the air-water interface in the cross-interface direction may be resolved over distances which are much smaller than the height of the waves themselves. We may account for the waves explicitly by employing a numerical spectral wave model, and applying a suitable theory of wave–mean flow interaction. If the mean flow is small compared with the wave phase speed, perturbation expansions of the hydrodynamic equations in a Lagrangian or generalized Lagrangian mean framework are useful: for stronger flows, such as for wind blowing over waves, the presence of critical levels where the mean flow velocity is equal to the wave phase speed necessitates the application of more general types of surface-following coordinate system. The interaction of the flow of air and water and associated differences in temperature and the concentration of various substances (such as gas species) gives rise to a complex boundary-layer structure at a wide range of vertical scales, from the sub-millimetre scales of gaseous diffusion, to several tens of metres for the turbulent Ekman layer. The bal- ance of momentum, heat, and mass is also affected significantly by breaking waves, which act to increase the effective area of the surface for mass transfer, and increase turbulent diffusive fluxes via the conversion of wave energy to turbulent kinetic energy.

关键词： wind-wave-current interaction coordinate systems upper-ocean turbulence air-sea exchange of momentum, heat, andmass

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Sessile serrated adenoma/polyps: Where are we at in 2016?

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World Journal of gastroenterology 2016年第34期22卷 7754-7759页

作者： Rajvinder Singh Leonardo Zorrón Cheng Tao Pu Doreen Koay alastair Burt gastroenterology Department Lyell Mc Ewin and Modbury HospitalNALHN School of MedicineUniversity of Adelaide gastrointestinal Endoscopy Division Department of GastroenterologyHospital das Clínicas da Faculdade de Medicina da Universidade de S?o Paulo gastroenterology Department Lyell Mc Ewin and Modbury HospitalUniversity of Adelaide Executive Dean Faculty of Health SciencesUniversity of Adelaide

It is currently known that colorectal cancers(CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway(50%-70%); the mutator "Lynch syndrome" route(3%-5%); and the serrated pathway(30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps(HP),sessile serrated adenomas/polyps(SSA/P) and traditional serrated adenomas(TSA),the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders,submucosal injection of a dye solution(for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions.

关键词： Colonoscopy Sessile serrated adenoma/ polyp Serrated lesion Colorectal polyps Colorectal cancer Polypectomy Image enhancing endoscopy Narrow band imaging Endocytoscopy

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A Rare Case of Non-small Cell Lung Carcinoma Squamous Phenotype with Epstein-Barr Virus Positivity with Prolonged Response to both Chemotherapy and Radiotherapy

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中国肺癌杂志 2021年第7期24卷 526-528页

作者： Carolina Navarro RODRIgUEZ Muhammad Shahid IQBAL Max ROBINSON graham BURNS alastair gREYSTOKE Department of Clinical Oncology Freeman Hospital Department of Pathology Freeman Hospital Department of Respiratory Medicine Royal Victoria Infirmary Department of Medical Oncology Northern Centre for Cancer CareThe Newcastle-upon-Tyne Hospitals NHS Foundation TrustNewcastle-upon-TyneUK

We present a rare challenging case of metastatic non-small cell lung cancer with Epstein-Barr virus positivity that was also diagnosed with pulmonary tuberculosis at the same time. Palliative chemotherapy gemcitabine and carboplatin was started after two weeks of anti-tuberculosis treatment with the hopes that this period would be sufficient to keep acid fast bacilli non-viable to minimise risk of tuberculosis re-activation due to chemotherapy induced immunosuppression. She completed four cycles of chemotherapy and six months of anti-tuberculosis treatment with good results and minimal side effects. Two years later, there was disease recurrence in cervical and mediastinal lymph nodes which was treated with local treatment i.e. surgery and palliative radiotherapy. It has been two years since last radiotherapy and overall more than five years since diagnosis with no active disease at present. given the complexity and rarity of this case, significant multidisciplinary team involvement, including oncologists and radiation oncologists, pulmonologists with special interest in tuberculosis and pathologists was necessary throughout.

关键词： Lung neoplasms Epstein-Barr Virus Tuberculosis Chemotherapy Radiotherapy

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Survival outcomes of cemented compared to uncemented stems in primary total hip replacement

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World Journal of Orthopedics 2014年第5期5卷 591-596页

作者： Michael Wyatt gary Hooper Christopher Frampton alastair Rothwell Department of Orthopaedic Surgery and Musculoskeletal Medicine University of Otago Christchurch Canterbury 8011 New Zealand

Total hip replacement(THR) is a successful and reliable operation for both relieving pain and improving function in patients who are disabled with end stage *** ageing population is predicted to significantly increase the requirement for THR in patients who have a higher functional demand than those of the past. Uncemented THR was introduced to improve the long term results and in particular the results in younger, higher functioning patients. There has been controversy about the value of uncemented compared to cemented THR although there has been a world-wide trend towards uncemented fixation. Uncemented acetabular fixation has gained wide acceptance, as seen in the increasing number of hybrid THR in joint registries, but there remains debate about the best mode of femoral *** this article we review the history and current worldwide registry data, with an in-depth analysis of the New Zealand Joint Registry, to determine the results of uncemented femoral fixation in an attempt to provide an evidence-based answer as to the value of this form of fixation.

关键词： Primary total hip replacement Femoral fixation Cemented Uncemented Joint replacement registry Implamt survival

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Osteopontin is an important mediator of alcoholic liver disease via hepatic stellate cell activation

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World Journal of gastroenterology 2014年第36期20卷 13088-13104页

作者： Devanshi Seth alastair Duly Paul C Kuo geoffrey W McCaughan Paul S Haber Drug Health Services Royal Prince Alfred Hospital Camperdown NSW 2050 Australia garvan Institute Darlinghurst NSW 2010 Australia Central Clinical School of Medicine the University of Sydney Sydney NSW 2050 Australia Department of Surgery Loyola University Medica Centre Maywood IL 60153 United States AW Morrow gastroenterology and Liver Centre RPAH Camperdown NSW 2050 Australia

AIM: To investigate over-expression of Osteopontin (OPN) pathway expression and mechanisms of action in human alcoholic liver disease (ALD), in vivo and in vitro acute alcohol models.

关键词： Hepatic stellate cells Liver cirrhosis Plasmin Steatosis Fibrogenesis Transforming growth factor β Osteopontin isoform

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非经典TgF-β信号转导的新发现和新进展

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中国药理学与毒理学杂志 2018年第11期32卷 839-840页

作者：斯图尔特.阿拉斯泰尔澳大利亚墨尔本大学亚太药理学家联合会

【超过10%的人口受哮喘影响。严重的类固醇依赖性哮喘患者大约有5%,却消耗了估计50%的费用。在过去30年中,哮喘治疗新方法仅有针对由Ⅱ型T辅助细胞因子驱动的所谓T2型哮喘,以及具有针对白细胞介素4、白细胞介素5或其受体的抗体。

关键词：信号转导抑制剂 CK TgF 哮喘患者

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Omics Approaches to Identify PotentialBiomarkers of Inflammatory Diseases in the FocalAdhesion Complex

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genomics, Proteomics & Bioinformatics 2017年第2期15卷 101-109页

作者： Johanne Brooks alastair Watson Tamas Korcsmaros gut Health and Food Safety Institute Strategic Programme Institute of Food Research Norwich Research Park Norwich NR4 7UA United Kingdom Norwich Medical School University of East Anglia Norwich Research Park Norwich NR4 7T J United Kingdom gastroenterology Department Norfolk and Norwich University Hospital Norwich NR4 7UY United Kingdom Earlham Institute Norwich Research Park Norwich NR4 7UZ United Kingdom

Inflammatory diseases such as inflammatory bowel disease(IBD) require recurrent invasive tests, including blood tests, radiology, and endoscopic evaluation both to diagnose and assess disease activity, and to determine optimal therapeutic strategies. Simple ‘bedside’ biomarkers could be used in all phases of patient management to avoid unnecessary investigation and guide further management. The focal adhesion complex(FAC) has been implicated in the pathogenesis of multiple inflammatory diseases, including IBD, rheumatoid arthritis, and multiple sclerosis. Utilizing omics technologies has proven to be an efficient approach to identify biomarkers from within the FAC in the field of cancer medicine. Predictive biomarkers are paving the way for the success of precision medicine for cancer patients, but inflammatory diseases have lagged behind in this respect. This review explores the current status of biomarker prediction for inflammatory diseases from within the FAC using omics technologies and highlights the benefits of future potential biomarker identification approaches.

关键词： Focal adhesion complex Biomarkers Inflammation Omics Systems biology

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