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AXL receptor signalling suppresses p53 in melanoma through stab.lization of the MDMX-MDM2 complex

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Journal of Molecular Cell b.ology 2017年第2期9卷 154-165页

作者： Anna de Polo Zhongling Luot Casimiro Gerarduzzi Xiang Chen john b. Little Zhi-Min Yuan john b. Little Center for Radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02115 USA Department of Dermatology Xiangya Hospital Central South University Changsha 410008 China

Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, b.t its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the sta- b.Uty of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpres- sion or activation through growth arrest-specific 6 （Gas6） Ugand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity. Upon activation, AXL stab.lizes MDMX through a post-translational modification that involves phosphoryl- ation of MDMX on the phosphosite Ser314, leading to increased affinity b.tween MDMX and MDM2 and favouring MDMX nuclear translocation. Ser314 phosphorylation can also protect MDMX from MDM2-mediated degradation, leading to stab.lization of the MDMX-MDM2 complex. We identified CDK4/6 and p38 MAPK as the two kinases mediating AXL-induced modulation of the MDMX-MDM2 complex, and demonstrated that suppression of AXL, either through siRNA silencing or pharmacological inhib.tion, increases expression levels of p53 target genes P21, MDM2, and PUMA, improves p53 pathway response to chemotherapy, and sensitizes cells to b.th Cisplatin and Vemurafenib. Our findings offer an insight into a novel signalling axis linking AXL to p53 and provide a potentially druggab.e pathway to restore p53 function in melanoma.

关键词： MDMX MDM2 AXL CDK4/6 p53 melanoma

Removal of Cryptosporidium sized particle under different filtration temperature, flow rate and alum dosing

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Journal of Harb.n Institute of Technology(New Series) 2007年第1期14卷 23-25页

作者：许国仁 Fitzpatrick S. b. Caroline Gregory john 邓林煜 School of Municipal and Environmental Engineering Harbin Institute of Technology Dept. of Civil and Environmental Engineering University College London Gower Street

Recent Cryptosporidium outb.eaks have highlighted concerns ab.ut filter efficiency and in particular particle b.eakthrough. It is essential to ascertain the causes of Cryptosporidium sized particle b.eakthrough for Cryptosporidium cannot b. destroyed b. conventional chlorine disinfection. This research tried to investigate the influence of temperature, flow rate and chemical dosing on particle b.eakthrough during filtration. The results showed that higher temperatures and coagulant doses could reduce particle b.eakthrough. The increase of filtration rate made the residual particle counts b.come larger. There was an optimal dose in filtration and was well correlated to ζ potential.

关键词： Cryptosporidium humic acid filtration particle temperature

Tracking invasion and invasiveness in Queensland fruit flies： From classical genetics to ＇omics＇

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Current Zoology 2015年第3期61卷 477-487页

作者： William b. SHERWIN Marianne FROMMER john A. SVED Kathryn A. RAPHAEL john G. OAKESHOTT Deb.rah C.A. SHEARMAN A. Stuart GILCHRIST Evolution and Ecology Research Centre University of NSW Sydney NSW 2052 Australia Murdoch University Cetacean Research Unit Murdoch University South Road Murdoch WA 6150 Australia CSIRO Land & Water Flagship Cltmies Ross St Canberra ACT 2601 Australia

Three Australian tephritid fruit flies （b.ctrocera tryoni - Q-fly, b.ctrocera neohumeralis - NEO, and b.ctrocera jarvisi - JAR） are promising models for genetic studies of pest status and invasiveness. The long history of ecological and physi- ological studies of the three species has b.en augmented b. the development of a range of genetic and genomic tools, including the capacity for forced multigeneration crosses b.tween the three species followed b. selection experiments, a draft genome for Q-fly, and tissue- and stage-specific transcriptomes. The Q-fly and NEO species pair is of particular interest. The distrib.tion of NEO is contained entirely within the wider distrib.tion of Q-fly and the two species are ecologically extremely similar, with no known differences in pheromones, temperature tolerance, or host-fruit utilisation. However there are three clear differences b.- tween them： humeral callus colour, complete pre-mating isolation b.sed on mating time-of-day, and invasiveness. NEO is much less invasive, whereas in historical times Q-fly has invaded southeastern Australia and areas of Western Australia and the North- em Territory. In southeastern fruit-growing regions, microsatellites suggest that some of these outb.eaks might derive from ge- netically differentiated populations overwintering in or near the invaded area. Q-fly and NEO show very limited genome diffe- rentiation, so comparative genomic analyses and QTL mapping should b. ab.e to identify the regions of the genome controlling mating time and invasiveness, to assess the genetic b.ses for the invasive strains of Q-fly, and to facilitate a variety of improve- ments to current sterile insect control strategies for that species

关键词： b.ctrocera Genomics STERILE-insect-technique Interspecific-hyb.idisation

Sleep Duration and Risk of Lung Cancer in the Physicians' Health Study

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中国肺癌杂志 2014年第9期17卷 649-655页

作者： Owais KHAWAJA Andrew b. PETRONE Sohaib.TEEM Kamran MANZOOR john MGAZIANO Luc DJOUSSE Section of Pulmonary and Critical Care Medicine Dartmouth Hitchcock Medical Center Lebanon USA Divisions of Aging Brigham and Women's Hospital and Harvard Medical School Boston USA Section of General Internal Medicine Dartmouth Hitchcodc Medical Center Lebanon USA Massachusetts Veterans Epidemiology and Research In/ormation Center (MAVERIC) Boston Veterans Affairs Healthcare System Boston USA Preventive Medicine Brigham and Women's Hospital and Harvard Medical Schoolp Boston USA Geriatric Research Education and Clinical Center (GRECC) Boston Veterans Affairs Heatthcare System Boston USA

b.ckground and Ob.ectives:Lung cancer is the most common cancer and cancer related cause of death ***,the association b.tween sleep duration and incident lung cancer has not b.en investigated in a prospective cohort ***:We prospectively examined the association b.tween sleep duration and incident lung cancer in a cohort of 21,026 United States(US)male ***-reported sleep duration was ascertained during 2002 annual follow-up *** lung cancer was ascertained through yearly follow-up *** regression was used to estimate relative risk of incident lung ***:The average age at b.seline was 68.3±8.8 *** a mean follow up of 7.5(±2.2)yr,150 cases of lung cancer *** 7 h of sleep as the reference group,multivariab.e adjusted hazard ratios(95%CI)for lung cancer were 1.18(0.77-1.82),1.0(ref),and 0.97(0.67-1.41)from lowest to the highest category of sleep duration(P for quadratic trend 0.697),*** a secondary analysis,smoking status did not modify the sleep duration-lung cancer association(P=0.78).There was no evidence for an interaction b.tween sleep duration and sleep apnea on the risk of lung cancer either(P=0.65).Conclusions:Our data failed to show a higher risk of lung cancer in association with altered sleep duration among US male physicians.

关键词：摘要编辑部编辑工作读者

Sifting for small primes from an arithmetic progression

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Science China Mathematics 2023年第12期66卷 2715-2730页

作者： john b.Friedlander Henryk Iwaniec Department of Mathematics University of TorontoTorontoON M5S 2E4Canada Department of Mathematics Rutgers UniversityPiscatawayNJ 08903USA

In this work and its sister paper(Friedlander and Iwaniec(2023)),we give a new proof of the famous Linnik theorem b.unding the least prime in an arithmetic *** sieve machinery in b.th papers,we are ab.e to dispensh with the log-free zero density b.unds and the repulsion property of exceptional zeros,two deep innovations b.gun b. Linnik and relied on in earlier proofs.

关键词： sieve small primes Linnik theorem

Highly cross-linked polyethylene is the new‘gold standard’b.aring material for total hip arthroplasty

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b.osurface and b.otrib.logy 2021年第2期7卷 53-59页

作者： john b.Medley Department of Mechanical and Mechatronics Engineering University of WaterlooWaterlooOntarioCanada

Conventional polyethylene is not used much in total hip arthroplasty(THA);it has b.en supplanted b. oxidation-resistant cross-linked polyethylene(≥50 kGy irradiation).However,studies persist that de-emphasize or ignore cross-linked polyethylene.A se-lective literature review is used b.iefly to present the early use of conventional poly-ethylene and its implication in wear particle-induced osteolysis leading to premature revision *** current situation is estab.ished b.sed on Australian registry data and other studies that advocate the use of cross-linked polyethylene in preference to conventional *** some studies suggest caution in using cross-linked polyethylene,overall it is strongly *** the author’s opinion,cross-linked polyethylene is the new reference standard b.aring material in THA.

关键词： cross Highly planted

VAPOR-LIQUID EQUILIb.IUM IN THE SYSTEM CARb.N DIOXIDE/ISO-PENTANE FROM 253 TO 443 K AT PRESSURES UP TO 10 MPa

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Chinese Journal of Chemical Engineering 1992年第2期 157-163页

作者：程华哲 john A. Zollweg William b. Streett b.ijing Research Institute of Chemical Industry School of Chemical Engineering Cornell University Ithaca NY14853 U.S.A.

Equilib.ium pressures and compositions for the b.nary mixture carb.n dioxide-iso-pentane were measured on nine isotherms from 253K to the iso-pentane critical temperature. On each isotherm, the entire pressure range of phase coexistence was covered. The mixture critical line has b.en located and is shown to b. contiuous in Pressure-Temperature-Composition (P-T-X) space b.tween the critical points of the pure components. Comparisons are made b.tween the experimental results ob.ained b. b.sserer-Rob.nson and this work with predictions of the Soave-Redlich Kwong, Peng-Rob.nson, Kub.c-Martin, and Adachi-Lu-Sugle cub.c equations of state. None was ab.e to correlate the data within our estimated experimental error.

关键词： iso-pentane carb.n dioxide phase equilib.ium

Specific features of Eu^(3+) and Tb.(3+) magnetooptics in gadolinium-gallium garnet (Gd_3Ga_5O_(12))

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Journal of Rare Earths 2011年第8期29卷 776-782页

作者： Uygun V. Valiev john b. Grub.r 付德君 Vasiliy O. Pelenovich Gary W. b.rdick Mariya E. Malysheva Faculty of Physics National University of Uzbekistan Department of Physics and Astronomy The University of Texas at San Antonio Department of Physics Wuhan University Department of Physics Andrews University

We reported magnetooptical properties of Eu3＋（4f（6）） and Tb.＋（4f（8）） in single crystals of Gd3Ga5O12 （GGG）, Y3Ga5O12 （YGG）, and Eu3＋（4f（6）） in Eu3Ga5O12 （EuGG） for b.th ions occupying sites of D2 symmetry in the garnet structure. Ab.orption, luminescence, and magnetic circular polarization of luminescence （MCPL） spectra of Tb.＋ in GGG and YGG and ab.orption and magnetic circular dichroism （MCD） of Eu3＋ in EuGG were studied. The data were ob.ained at 85 K and room temperature （RT）. Magnetic susceptib.lity of Eu3＋ in EuGG was also measured b.tween 85 K and RT. The magnetooptical and magnetic susceptib.lity data were modeled using the wavefunctions of the crystal-field split energy （Stark） levels of Eu3＋ and Tb.＋ occupying D2 sites in the same garnets. The results reported gave a precise determination of these Stark level assignments and confirmed the symmetry lab.ls （irreducib.e representations） of the closely-spaced Stark levels （quasi-doub.ets） found in the 5D1 （Eu3＋） and 5D4 （Tb.＋） multiplets. Ultraviolet （UV） excitation （300 nm） of the 6PJ and 6IJ states of Gd3＋ in the doped GGG crystals led to emission from 5D4 （Tb.＋） and 5D1 and 5D0 （Eu3＋） through radiationless energy transfer to the 4f（n–1）5d b.nd of Tb.＋ and to UV quintet states of Eu3＋. The temperature-dependent emission line shapes and line shifts of the magnetooptical transitions excited b. UV radiation suggested a novel way to explore energy transfer mechanisms in this rare-earth doped garnet system.

关键词： magnetic circular polarization of luminescence magnetic circular dichroism ab.orption quantum qutting energy transfer magnetic susceptib.lity rare earths

Mathematical Challenges to Macroevolution

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Journal of Applied Mathematics and Physics 2022年第11期10卷 3385-3391页

作者： john b. Andelin Williston North Dakota USA

The theory of evolution was advanced b. Darwin in 1859, prior to Mendel’s experiments demonstrating the particulate nature of inheritance. The modern synthesis was formulated in the early 1940s, well b.fore the concept of coded information was understood. This paper outlines four mathematical challenges to the modern synthesis, which are b.sed on current understanding of the proposed mechanisms of evolutionary change within the constraints of experimental molecular b.ology.

关键词： Evolution Convergence Prob.b.lity b.nomial Distrib.tion Formula Ex Post Facto Prob.b.lity Post-Hoc Prob.b.lity Modern Synthesis