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Discussion of some‘knowns’and some‘unknowns’about the tumour suppressor p53

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Journal of Molecular Cell Biology 2019年第3期11卷 212-223页

作者： Elizabeth Lieschke Zilu Wang Gemma L kelly Andreas Strasser The Walter and Eliza Hall Institute of Medical research Melbourne 3052Australia Department of Medical Biology University of MelbourneMelbourne 3050Australia

Activation of the tumour suppressor p53 upon cellular stress can induce a number of different cellular processes?The diverse actions of these processes are critical for the protective function of p53 in preventing the development of ***,it is still not fully understood which process(es)activated by p53 is/are critical for tumour suppression and how this might differ depending on the type of cells undergoing neoplastic transformstion and the nature of the drivers of ***,it is not clear why upon activation of p53 some cells undergo cell cycle arrest and senescence whereas others die by *** we discuss some of the cellular processes that are crucial for p53-mediated tumour suppression and the factors that could impact cell fate upon p53 ***,we describe therapies aimed either at activating wild-type p53 or at changing the behaviour of mutant p53 to unleash tumour growth suppressive processes for therapeutic benefit in malignant disease.

关键词： p53 tumour suppression cell death cell cycle arrest/senescenee

Back to school after lockdown: The effect of COVID-19 restrictions on children’s device-based physical activity metrics

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Journal of Sport and Health Science 2022年第4期11卷 530-536页

作者： Liezel Hurter Melitta McNarry Gareth Stratton kelly Mackintosh Applied Sports TechnologyExercise and Medicine Research Centre(A-STEM)Swansea UniversitySwansea SA18ENUK

Background:The coronavirus disease-2019(COVID-19) pandemic and national lockdowns took away opportunities for children to be physically *** study aimed to determine the effect of the COVID-19 lockdown on accelerometer-assessed physical activity(PA) in children in ***:Eight hundred participants(8-18 years old),stratified by sex,age,and socio-economic status,wore Axivity AX3 accelerometers for7 days in February 2021,during the lockdown,and in May 2021,while in *** accelerometer data were processed in r-package GGIr,and cut-point data,average acceleration(AvAcc),intensity gradient,and the acceleration above which the most active X minutes are accumulated(MX) metrics were *** mixed models were used to assess the influence of time-point,sex,age,and socioeconomic status(SES) on ***:During lockdown,moderate-to-vigorous PA was 38.4±24.3 min/day;sedentary time was 849.4±196.6 min/day;mean± *** levels increased significantly upon return to school(all variables p re were no sex differences during lockdown(p=0.233),girls engaged in significantly less moderate-to-vigorous PA than boys once back in school(p rthermore,boys had more favorable intensity profiles than girls(intensity gradient:p regardless of *** levels decreased with age at both time-points;upper secondary school girls were the least active group,with an average M30 of 195.2 mg(while in school).Conclusion:The lockdown affected boys more than girls,as reflected by the disappearance of the typical sex difference in PA levels during lockdown,although these were re-established on return to *** secondary school(especially girls) might need specific COVID-recovery intervention.

关键词： Accelerometer Intensity gradient MX metrics

Geotechnical investigation of low-plasticity organic soil treated with nano-calcium carbonate

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Journal of rock Mechanics and Geotechnical Engineering 2023年第2期15卷 500-509页

作者： Govindarajan Kannan Brendan C.O’kelly Evangelin ramani Sujatha Centre for Advanced research in Environment School of Civil EngineeringSASTRA Deemed to be UniversityThanjavurTamil Nadu613401India Department of Civil Structural and Environmental EngineeringTrinity College DublinDublinD02 PN40Ireland

Soil stabilization using nanomaterials is an emerging research area although,to date,its investigation has mostly been laboratory-based and therefore requires extensive study for transfer to practical field *** present study advocates nano-calcium carbonate(NCC)material,a relatively unexplored nanomaterial additive,for stabilization of low-plasticity fine-grained soil having moderate organic *** plasticity index,compaction,unconfined compressive strength(UCS),compressibility and permeability characteristics of the 0.2%,0.4%,0.6%and 0.8%NCC-treated soil,and untreated soil(as control),were determined,including investigations of the effect of up to 90-d curing on the UCS and permeability *** terms of UCS improvement,0.4%NCC addition was identified as the optimum dosage,mobilizing a UCS at 90-d curing of almost twice that for the untreated *** treated soil,particle aggregation arising from NCC addition initially produced an increase in the permeability coef-ficient,but its magnitude decreased for increased curing owing to calcium silicate hydrate(CSH)gel formation,although still remaining higher compared to the untreated soil for all dosages and curing periods *** index decreased for all NCC-treated soil *** micro-graphs indicated the presence of gel patches along with particle aggregation.X-ray diffraction(XrD)results showed the presence of hydration products,such as *** increases in UCS are initially attributed to void filling and then because of CSH gel formation with increased curing.

关键词： Organic silt Calcium carbonate Nano-calcium carbonate(NCC) Calcium silicate hydrate(CSH) Soil stabilization

Determinants of Online Buying Behaviour of Social Media Users in Cameroon

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Journalism and Mass Communication 2024年第2期14卷 112-139页

作者： kelly E.Ade Stephen N.Ndode Kingsley L.Ngange University of Buea BueaCameroon

Online shopping in Cameroon is growing rapidly and gaining considerable *** phenomenon is relatively new as compared to the traditional brick-and-mortar store(serving customers face-to-face in a building rather than online).As the world faces digital transformations,businesses in Cameroon are seeking new ways to reach their customers and create favourable environments to effectively carryout online *** study examines the factors that affect consumer online buying behaviour in *** theories guided this investigation:the Technology Acceptance Model(Davis,1989),Diffusion of Innovations Theory(rogers,1995),and Uses and Gratifications Theory(Katz&Blumler,1974).The study focuses on students of the University of Buea who carry out online *** sampling is used,and data are collected from 365 respondents through a questionnaire with open and closed ended *** of data is done with the use of the Statistical Package for Social Scientists(SPSS)Version 21 to determine the types of products consumers buy online;the degree to which consumer trust and satisfaction affect consumer loyalty;and the specific social,economic,and market factors that affect online buying *** indicate that:Consumers mostly buy fashion items(74.3%),electronics(44.7%),cosmetics(37.3%),and house equipment(34%)*** will repeat purchase from a marketer if they trust and are satisfied with the product and service quality(81.1%);hence,they will also encourage others to *** they are dissatisfied,they will not repeat purchase from the online ***(76.1%),attractive pricing/discount(71.7%),product quality(71%),service quality(64.1%),convenience(72.3%),available income/money(49.6%),word of mouth recommendation(41.9%),and personal motivation(62.7%)constitute the major factors that affect consumer online buying *** of the hypotheses testing show that:H1=Consumers buy more of fashion items online(X^(2)=9.950;

关键词： online shopping consumer buying behaviour online trust and satisfaction technology Cameroon

Exhaustion and Emotional Demands in China： A Large-Scale Investigation across Occupations

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Frontiers of Business research in China 2017年第1期11卷 45-68页

作者： kelly Z. Peng Department of Business Administration Hong Kong Shue Yan University Hong Kong China

As the Chinese economy moves toward a market-based model, employees are likely to face more emotional demands and exhaustion at work. However, there are some unique aspects to the emotional demands of work in the Chinese cultural context. We investigate emotional demands and exhaustion in China with a large-scale sample across the six major occupations identified by the Holland classification system. results show that incumbents of social and enterprising jobs face higher emotional demands. Unexpectedly, exhaustion differs significantly between conventional and other types of jobs. Building on the Job Demand-resources （JD-r） model, job crafting and the cultural context, we propose that the nonlinear relationship of emotional demands and exhaustion exists only when emotional intelligence is low. Our study may inform practitioners and policy makers in Chinese enterprises about emotional demands and exhaustion for various occupations and the importance of selection and training programs in emotional intelligence.

关键词： exhaustion burnout emotional demands emotional intelligence JD-r model

Intermittent swelling and shrinkage of a highly expansive soil treated with polyacrylamide

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Journal of rock Mechanics and Geotechnical Engineering 2022年第1期14卷 252-261页

作者： Amin Soltani An Deng Abbas Taheri Brendan C.O’kelly School of Engineering Information Technology and Physical SciencesFederation UniversityChurchillVIC3842Australia School of Civil Environmental and Mining EngineeringThe University of AdelaideAdelaideSA5005Australia Department of Civil Structural and Environmental EngineeringTrinity College DublinDublinD02 PN40Ireland

This laboratory study examines the potential use of an anionic polyacrylamide(PAM)-based material as an environmentally sustainable additive for the stabilization of an expansive soil from South *** experimental program consisted of consistency limits,sediment volume,compaction and oedometer cyclic swell-shrink tests,performed using distilled water and four different PAM-to-water solutions of P_(D)=0.1 g/L,0.2 g/L,0.4 g/L and 0.6 g/L as the mixing ***,the relative swelling and shrinkage strains were found to decrease with increasing number of applied swell-shrink cycles,with an‘elastic equilibrium’condition achieved on the conclusion of four *** propensity for swelling/shrinkage potential reduction(for any given cycle)was found to be in favor of increasing the PAM dosage up to P_(D)=0.2 g/L,beyond which the excess PAM molecules self-associate as aggregates,thereby functioning as a lubricant instead of a flocculant;this critical dosage was termed‘maximum flocculation dosage’(MFD).The MFD assertion was discussed and validated using the consistency limits and sediment volume properties,both exhibiting only marginal variations beyond the identified MFD of P_(D)=0.2 g/*** accumulated axial strain progressively transitioned from‘expansive’for the unamended soil to an ideal‘neutral’state at the MFD,while higher dosages demonstrated undesirable‘contractive’states.

关键词： Expansive soil Polyacrylamide(PAM) Consistency limits Sediment volume Swell-shrink cycles Swelling and shrinkage strains Accumulated axial strain

Calibration of Modified Spalart-Allmaras Model Parameters for Linear Compressor Cascade Corner Flow

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Journal of Thermal Science 2022年第1期31卷 163-172页

作者： MATSUI Kotaro PErEZ Ethan kelly T.ryan TANI Naoki JEMCOV Aleksandar IHI Corporation Notre Dame Turbomachinery Laboratory Department of Aerospace and Mechanical Engineering University of Notre Dame

In this study, Bayesian parameter calibration is applied to Saplart-Allmaras(SA) turbulence model, and the prediction improvement by the calibrated model is demonstrated. The quantity of interest(QOI) is the pitch-wise distribution of Mach number in the corner separation flow region. The 10 model parameters included in the SA model with rotation-Curvature correction are considered as random variables obeying uniform prior probability distributions. The order of generalized Polynomial Chaos(g PC) used for sensitivity analysis and surrogate model in calibration is incrementally increased during the calibration process. Posterior convergence is obtained at the 3 rd order expansion level in this study. At this final level, sensitivity analysis indicates 3 model parameters, cb1, κ and cr3 are the most influential random variables, and 3-parameter Bayesian calibration is conducted. The likelihood function in the Bayesian theorem is specified in the form of Gaussian distribution, including experimental uncertainty. The combination of prior and likelihood brings the posterior distribution of model parameters, and Maximum A Posterior(MAP) value is selected as a calibrated parameter set. The flow simulation with calibrated parameters shows a significant increase in the accuracy of the Mach number profile in the corner separation region. The increase in accuracy is attributed to enlarged turbulent viscosity due to the parameter modification of the turbulent viscosity source term. The calibrated parameter is also tested in the off-design flow field, not included in the calibration process. The calibrated CFD again shows improved accuracy for corner separation prediction, and the effectiveness of the parameter set outside of the calibration field is demonstrated.

关键词： compressor corner flow turbulence model calibration

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

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World Journal of Gastroenterology 2017年第1期23卷 141-150页

作者： Tisha r Joy Charles A McKenzie rommel G Tirona kelly Summers Shannon Seney Subrata Chakrabarti Neel Malhotra Melanie D Beaton Department of Medicine Division of EndocrinologySt.Joseph’s HospitalWestern University Department of Medical Biophysics Western University Department of Physiology and Pharmacology Western University Department of Microbiology and Immunology Western University Department of Pathology and Laboratory Medicine Western University Department of Medicine Division of GastroenterologyLondon Health Sciences CentreWestern University

AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MrI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MrI technique] and changes in hepatic steatosis on liver *** was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) n

关键词： Sitagliptin randomized controlled trial Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Fibrosis Magnetic resonance imaging Hepatic steatosis Insulin resistance Platelet aggregation

Prostate cancer biomarker： a key field to explore

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Asian Journal of Andrology 2013年第3期15卷 358-359页

作者： Jianqing Lin Hushan Yang William K kelly Department of Medical Oncology Jefferson Kimmel Cancer Center Thomas Jefferson University Philadelphia PA 19107 USA

In order to achieve personalized cancer care, tools are needed to predict benefitfrom a specific therapy. Prostate cancer bio- marker study is a key field to explore so that the natural course of a patient＇s disease can be predicted. A panel of inflammation/ immune-related and prostate cancer-related genes was screened by ross et al. to assess genes predictive of castration-resistant pro- state cancer （CrPC） survival. They found that a six-gene model was superior to tm- ditionaUy used clinic-pathological variables. Although the clinic utility of this model remains to be determined, the blood based technical achievement and potential may eventually improve personalized cancer care.

关键词： PErIPHErAL-BLOOD CELLS PrOGNOSTIC MODEL EXPrESSION MICrOArrAY MEN