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Small molecule activators of the p53 response

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Journal of Molecular Cell Biology 2019年第3期11卷 245-254页

作者： marcus J.G.w.Ladds Sonia Lain Department of Microbiology Tumor and Cell BiologyBiomedicumSolnavagen 9Karolinska Institutet17165StockholmSweden SciLifeLab Tomtebodavagen 23A171 65SoinaStockholmSweden

Drugging the p53 pathway has been a goal for both academics and pharmaceutical companies since the designation of p53 as the'guardian of the genome'.Through growing understanding of p53 biology,we can see multiple routes for activation of both wild-type p53 function and restoration of mutant p53?In this review,we focus on small molecules that activate wild-type p53 and that do so in a nongenotoxit *** particular,we will describe potential approaches to targeting proteins that alter p53 stability and function through posttranslational modification,affect p53's subcellular localization,or target RNA synthesis or the synthesis of *** plethora of pathways for exploitation of p53,as well as the wide-ranging response to p53 activation,makes it an attractive target for anti-cancer therapy.

关键词： cancer p53 small molecule cell biology cancer therapy

Enhanced apoptosis in post-liver transplant hepatitis C:Effects of virus and immunosuppressants

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world Journal of Gastroenterology 2012年第18期18卷 2172-2179页

作者： Eu Jin Lim Ruth chin Peter w Angus Joseph Torresi Liver Transplant Unit Austin HospitalHeidelbergVictoria 3084Australia Department of Medicine University of MelbourneAustin HealthHeidelbergVictoria 3084Australia Department of Infectious Diseases Austin HospitalHeidelbergVictoria 3084Australia

Hepatitis C(HCV)-infected patients have a poorer survival post-liver transplantation compared to patients transplanted for other indications,since HCV recurrence post-transplant is universal and commonly follows an aggressive *** is increasing evidence that in the non-transplant setting,induction of hepatocyte apoptosis is one of the main mechanisms by which HCV drives liver inflammation and fibrosis,and that HCV proteins directly promote *** studies have shown that post-liver transplant,there is a link between high levels of HCV replication,enhanced hepatocyte apoptosis and the subsequent development of rapidly progressive liver *** the responsible mechanisms remain unclear,it is likely that immunosuppressive drugs play an important *** is well known that immunosuppressants impair immune control of HCV,thereby allowing increased viral *** there is also evidence that immunosuppressants may directly induce apoptosis and this may be facilitated by the presence of high levels of HCV *** HCV and immunosuppressants may synergistically interact to further enhance apoptosis and drive more rapid *** findings suggest that modulation of apoptosis within the liver either by changing immunosuppressive therapy or the use of apoptosis inhibitors may help prevent fibrosis progression in patients with post-transplant HCV disease.

关键词： Hepatitis C Liver transplantation Apoptosis Immunosuppressive agents transforming growth factor-β

Ultracold atomic gases going strong

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National Science Review 2016年第2期3卷 168-170页

作者： Cheng chin James Franck Institute Enrico Fermi InstituteUniversity of Chicago

The year 2015 marks the 20th anniversary of the achievement of Bose-Einstein condensation(BEC)in atomic *** BEC,realized by Eric Cornell,Carl wieman and wolfgang Ketterle in1995,commenced an exciting wave to explore quantum few-and many-body *** from solid state matter and helium superfluids,atomic condensates in the gas phase come with

关键词： body BEC Ultracold atomic gases going strong length

Modulating neuronal plasticity with choline

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Neural Regeneration Research 2019年第10期14卷 1697-1698页

作者： Eunice w. M. chin Eyleen L.K. Goh Neuroscience Academic Clinical Programme Duke-NUS Medical SchoolSingaporeSingapore Department of Research National Neuroscience InstituteSingaporeSingapore

The American psychologist william James once wrote that nervous tissue seems to be endowed with a “very extraordinary” degree of plasticity. To be plastic means to be capable of being molded, receiving shape, or being made to assume a desired form. This can be achieved consequential to changes in the internal and/or external environment. Being plastic, neurons are highly able to amend their structural and functional output, through alteration of their morphology, activation of intracellular signaling cascades, regulation of synaptic density and neurotransmitter release, or a combination of these events.

关键词： The American psychologist tissue seems to be endowed combination of these events

Can Labor Out-Migration Reduce Firewood Consumption by Rural Households in western Mountainous china

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chinese Journal of Population,Resources and Environment 2012年第2期10卷 110-119页

作者： Tai Xiujun LiShuzhuo marcus w. Feldman School of Economics and Management Shanxi Normal University Linfen Shanxi 041000 China Institute for Population and Development Studies School of Public Policy and Administration Xi'an Jiaotong University Xi'an Shaanxi 710049 China Morrison Institute for Population and Resource Studies Stanford University CA 94305 United States

The relationship between out-migration of labor in the Qinling mountain area and households' firewood consumption is explored. Migration and remittances reduce households' firewood consumption due to increases in both income and opportunity cost of firewood collection. Previous studies have been equivocal because they ignored uncertainty in household economy, which is widespread in forest areas of less developed countries. This study provides additional insight by considering vulnerability and subjective assessment of poverty generated by unstable income and an uncertain future. we provide evidence that the amount of firewood consumed depends on income and opportunity cost of firewood collection, but also on a prudent consumption strategy, due to farmers' subjective assessment of their future possible poverty. we also find out-migration of labor can reduce per capita firewood consumption but subjective poverty also acts against reduction of firewood consumption.

关键词： migration vulnerability firewood rural households

A 32-gene risk index： a new prognostic approach for prostate cancer progression

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Asian Journal of Andrology 2013年第5期15卷 590-591页

作者： Chao Cai wei-De Zhong w. Scott McDougal chin-Lee wu Department of Urology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA Graduate School of Southern Medical University Guangzhou Guangdong 510515 China Department of Urology Guangzhou First Municipal People's Hospital Guangzhou Guangdong 510180 China Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA

Radical prostatectomy （RP） has been a widely accepted and standard treat-ment for clinically localized and locally advanced prostate cancer. However, effective clinical management of RP patient remains being challenged, given that conventional prognostic factors, including Gleason score, pT stage, surgical margin status and presurgery serum prostatespecific antigen （PSA）,

关键词： A 32-gene risk index prognostic approach prostate cancer progression

Studying neurological disorders using induced pluripotent stem cells and optogenetics

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Neural Regeneration Research 2015年第11期10卷 1720-1722页

作者： Eunice w.M.chin Eyleen L.K.Goh Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore NUS Graduate School for Integrative Singapore Sciences and Engineering National University of Singapore Department of Physiology Yong Loo Lin School of Medicine National University of Singapore KK Research Center KK Women’s and Children’s HospitalSingapore

Neurological disorders are amongst the most widely studied human ***,they are also one of the most poorly *** most of these disorders are polygenic,genotype still plays an important role in their *** example,in schizophrenia and autism spectrum disorders,there is a 40-60%concordance rate in monozygotic twins,with 60-90%heritability（Burmeister et al.,2008）.However,the mechanisms by which multiple genes and their genomic variations influence the phenotypes of the disorders remain to be understood. The complexities of the disorders are tur- ther compounded by the individual rarity of the genomic variations and their variable penetrance （Cook and Scherer, 2008）. Thus, conventional disease modeling, such as gene knockout in cells or in animals, to attain the desired disease genotype may not be the most suitable platform for tackling most neurological disorders.

关键词： PSCs cell stem Studying neurological disorders using induced pluripotent stem cells and optogenetics

Temperature Measurement of Small Objects by Mach-Zehnder Interferometer

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Journal of Thermal Science 1993年第4期2卷 270-274页

作者： Y.T.wong w.K.chin Hong Kong Polytechnic

A Mach-Zehnder Interferometer incorporated with image processing has been set up to study the temperature field of small *** objects with width to height ratios ranging from 0.33 to 1.0 subjected to natural convection are used to simulate the condition at which the end effects are significant. Interferogram representing the temperature gradient is captured,digitized,and image processed with the aid of an image processing unit.A simple correction model is proposed to treat the stored interferometric *** interference data are found to compare well with those provided by the thermocouples.

关键词： temperature measurement small objects mach-zehnder interferometer

Vibrational characteristics of piping system in air conditioning outdoor unit

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Science china(Technological Sciences) 2011年第5期54卷 1154-1168页

作者： S. K. LOH w. F. FARIS M. HAMDI w. M. chin Department of Engineering Design & Manufacture Faculty of Engineering University of Malaya Department of Mechanical Engineering College of Engineering International Islamic University Malaysia O.Y.L. R&D Sdn Bhd Sungai Buloh Selangor Darul Ehsan Malaysia

The modal analysis of piping system in air conditioner (AC) outdoor unit is essential to investigate the vibration properties of the system. In view of the growing significance of numerical finite element (FE) model for vibration behaviour prediction, the AC piping elastic end support characterization has been explored. The axial and radial stiffness variables (ka, kr1, kr2) of the compressor-piping mounting are obtained and represented by dynamic stiffness of compressor grommet. They are obtained from dynamic load deflection test based on compressor operating condition such as excitation frequency and amplitude. The unknown stiffness variables of the other tube end (chassis-piping mounting) are determined by parameter fine tuning. An experimental modal analysis using impact hammer test has also been employed to determine the vibration properties such as natural frequencies, mode shapes and damping ratio of the piping structures. The modal parameters acquisition using SCADAS mobile acquisition system and LMS Impact Testing software is compared with the corresponding simulated modal properties using Abaqus. Most of the simulated natural frequencies achieve good correlation with the measured frequencies and it is reasonably a good prediction model to predict vibration behaviour of AC piping structures.

关键词： air conditioning outdoor unit piping modal analysis vibration characteristics