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Gemcitabine Inhibits Murine Head and Neck Squamous Cell Carcinoma Growth via Proteasome-Dependent Degradation of Chk1 Leading to Cell Cycle Arrest and Apoptosis

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Journal of Cancer Therapy 2012年第5期3卷 562-574页

作者： Anren Song Jean Wu Emily Whitaker nadarajah vigneswaran Department of Diagnostic and Biomedical Sciences School of Dentistry University of Texas Health Science Center at Houston Houston USA Medical Student Washington University School of Medicine in St. Louis St. Louis USA

Head and neck squamous cell carcinoma (HNSCC) is a common tumor worldwide that often presents at an advanced stage with poor prognosis. Advanced HNSCC frequently exhibits resistance to chemotherapy limiting its efficacy. Gemcitabine is a pyrimidine-based analog that is currently used for the treatment of metastatic pancreatic cancer. In this study, we examined the anti-tumor effects of gemcitabine in a highly aggressive murine model of HNSCC (LY2). In vitro cell viability and in vivo tumor growth inhibitory assays were carried out to determine the sensitivity of LY2 cells to gemcitabine. Immunohistochemical, Western blotting, RT-PCR and RNAi-mediated silencing assays were used to characterize effects of gemcitabine cell proliferation, DNA synthesis, apoptosis, pro-survival and DNA damage response signaling pathways. LY2 cells treated with gemcitabine undergo apoptosis mediated by the activation of both caspase-3 and -9. Gemcitabine on treatment induces rapid phosphorylation of checkpoint kinase 1 (Chk1) in LY2 cells and subsequent degradation in a time and dose dependent manner. Proteasome inhibitor MG132 blocks Chk1 degradation and decreases LY2 cells susceptibility to gemcitabine. Inhibition of Chk1 function, either using inhibitor PD 407824 or small interfering RNA (siRNA), increases the sensitivity of LY2 cells to gemcitabine. Gemcitabine treatment resulted in significant reduction in tumor growth relative to saline-treated control in a syngeneic orthotopic murine model of HNSCC. Gemcitabine-induced DNA replication stress in LY2 cells activates Chk1 by phosphorylation and promotes Chk1 degradation via the ubiquitin-proteasome pathway. Depletion of Chk1 terminates S-phase check point in LY2 cells resulting in apoptotic cell death. Our data provides an important rationale for integrating gemcitabine to optimize chemotherapeutic efficacy in HNSCC.

关键词： Chk1 Gemcitabine Head and Neck Cancer Apoptosis siRNA

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Gemcitabine Inhibits Murine Head and Neck Squamous Cell Carcinoma Growth via Proteasome-Dependent Degradation of Chk1 Leading to Cell Cycle Arrest and Apoptosis

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Journal of Cancer Therapy（癌症治疗） 2012年第5期

作者： Anren Song Jean Wu Emily Whitaker nadarajah vigneswaran

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SOME POSTERIOR DISTRIBUTIONS FOR THE LAPLACE MEAN

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Acta Mathematica Scientia 2010年第1期30卷 330-340页

作者： Saralees nadarajah School of Mathematics University of ManchesterManchester M13 9PLUK

Two posterior distributions for the mean of the Laplace distribution are obtained by deriving the distributions of the product XY and the ratio X/Y when X and Y are Student＇s t and Laplace random variables distributed independently of each other. Tabulations of the associated percentage points are given along with computer programs for generating them.

关键词： Laplace distribution posterior distribution for the Laplace mean productof random variables ratio of random variables

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Expansions for the Distribution and the Maximum from Distributions with an Asymptotically Gamma Tail When a Trend Is Present

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Acta Mathematica Sinica,English Series 2015年第3期31卷 526-542页

作者： Christopher S.WITHERS Saralees nadarajah Industrial Research Limited University of Manchester

We give expansions about the Gumbel distribution in inverse powers of n and logn for Mn, the maximum of a sample size n or n ＋ 1 when the j-th observation is μ（j/n）＋ ej, μ is any smooth trend flmction and the residuals {ej} are independent and identically distributed with P（e〉r）≈exp（-δx）x^do ∑k=1 ∞ckx^-kβ as -x→∞. We illustrate practical value of the expansions using simulated data sets.

关键词： Bell polynomials expansions exponential and gamma tails Gumbel maximum trend

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The Pickands' Estimator of the Negative Extreme-value Index

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北京大学学报（自然科学版） 2001年第1期37卷 12-19页

作者：彭作祥 S nadarajah 西南师范大学数学系重庆市400715 Department of Statistics

提出一类极值指数为负时的相似于Pickand’s型的新的极值指数估计量。

关键词：渐近分布相合性极值批数负极值指标 PICKANDS估计估计量

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Skew t distribution and its moments

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Progress in Natural Science:Materials International 2006年第10期16卷 1033-1037页

作者： Saralees nadarajah Arjun K.GUPTA Department of Statistics University of NebraskaLincolnNE 68583USA Department of Mathematics and Statistics Bowling Green State UniversityBowling GreenOH 43403USA

A random variable X is said to have the skew-t distribution if its pdf is f(x) = 2g(x) G(λx ), where g(·) and G (·), respectively, denote the pdf and the cdf of the Student' s t distribution with degrees of freedom v. The moments of this distribution appear not to have been studied in detail. In this paper, we derive general expressions for the nth moment of X by considering the cases v odd and v even separately. These expressions turn out to involve sums of the Gauss hypergeometric function. We also provide closed form expressions for the moments of X for the particular cases v = 2,66666, 10.

关键词： complete elliptical integral of the first kind complete elliptical integral of the second kind Gauss hypergeometric function moments skew t distribution.

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Understanding association between methylene blue dye and biosorbent: Palmyrah sprout casing in adsorption process in aqueous phase

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Water Science and Engineering 2023年第2期16卷 154-164页

作者： D.M.N.H.Jayasuriya Kannan nadarajah Department of Agricultural Engineering Faculty of AgricultureUniversity of JaffnaAriviyal NagarKilinochchi 44000Sri Lanka

Water pollution caused by industrial dyes has become a severe problem in the modern world. Biosorbents can be used in an eco-friendly manner to remove industrial dyes. In this study, five biosorbents were selected: palmyrah sprout casing (PSC), manioc peel, lime peel, king coconut husk, and coconut kernel. Batch adsorption experiments were conducted to identify the best biosorbent with the highest ability to adsorb methylene blue (MB) from wastewater. The detailed mechanisms of PSC used in the adsorptive removal of MB in aqueous phase were investigated. Of the five biosorbents, PSC exhibited the best removal performance with an adsorption capacity at equilibrium (qe) of 27.67 mg/g. The qe values of lime peel, king coconut husk, manioc peel, and coconut kernel were 24.25 mg/g, 15.29 mg/g, 10.84 mg/g, and 7.06 mg/g, respectively. To explain the mechanisms of MB adsorption with the selected biosorbents, the Fourier transform infrared (FTIR) spectrometry and X-ray diffraction (XRD) analyses were performed to characterize functional properties, and isotherm, kinetic, rate-limiting, and thermodynamic analyses were conducted. The FTIR analysis revealed that different biosorbents had different functional properties on their adsorptive surfaces. The FTIR and XRD results obtained before and after MB adsorption with PSC indicated that the surface functional groups of carbonyl and hydroxyl actively participated in the removal process. According to the isotherm analysis, monolayer adsorption was observed with the Langmuir model with a determination coefficient of 0.998. The duration to reach the maximum adsorption capacity for MB adsorption with PSC was 120 min, and the adsorption process was exothermic due to the negative enthalpy change (-9.950 kJ/mol). Moreover, the boundary layer thickness and intraparticle diffusion were the rate-limiting factors in the adsorption process. As a new biosorbent for MB adsorption, PSC could be used in activated carbon production to enhance the

关键词： Biosorbents Isotherm Kinetics Methylene blue Rate-limiting factor Thermodynamics

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Moments of the folded logistic distribution

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Progress in Natural Science:Materials International 2007年第6期17卷 696-697页

作者： Saralees nadarajah Samuel Kotz School of Mathematics University of ManchesterManchester M60 1QDUK Department of Engineering Management and Systems Engineering George Washington UniversityWashingtonDC 20052USA

The recent paper by Cooray et al. introduced the folded logistic distribution. The moments properties given in the paper appear too complicated. In this note, a simple formula is derived in terms of the well known Ler... 详细信息

关键词： folded logistic distribution Lerch function moments.

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Deep reinforcement learning with planning guardrails for building energydemand response

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能源与人工智能(英文) 2023年第1期11卷 12-25页

作者： Doseok Jang Lucas Spangher Selvaprabu nadarajah Costas Spanos Department of Electrical Engineering and Computer Science University of California at BerkeleyBerkeley94704CAUSA Department of Information and Decision Sciences University of Illinois at ChicagoChicago60607ILUSA

Building energy demand response is projected to be important in decarbonizing energy use. A demand responseprogram that communicates ‘‘artificial’’ hourly price signals to workers as part of a social game has the potentialto elicit energy consumption changes that simultaneously reduce energy costs and emissions. The efficacy ofsuch a program depends on the pricing agent’s ability to learn how workers respond to prices and mitigatethe risk of high energy costs during this learning process. We assess the value of deep reinforcement learning(RL) for mitigating this risk. Specifically, we explore the value of combining: (i) a model-free RL method thatcan learn by posting price signals to workers, (ii) a supervisory ‘‘planning model’’ that provides a syntheticlearning environment, and (iii) a guardrail method that determines whether a price should be posted to realworkers or the planning environment for feedback. In a simulated medium-sized office building, we compareour pricing agent against existing model-free and model-based deep RL agents, and the simpler strategy ofpassing on the time-of-use price signal to workers. We find that our controller eliminates 175,000 US Dollarsin initial investment, decreases by 30% the energy cost, and curbs emissions by 32% compared to energyconsumption under the time-of-use rate. In contrast, the model-free and model-based deep RL benchmarksare unable to overcome initial learning costs. Our results bode well for risk-aware deep RL facilitating thedeployment of building demand response.

关键词： Deep reinforcement learning Risk-aware planning Demand response Energy Decarbonization

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The exponentiated generalized power Lindley distribution: Properties and applications

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Applied Mathematics(A Journal of Chinese Universities) 2019年第2期34卷 127-148页

作者： S.M.T.K. MirMostafaee Morad Alizadeh Emrah Altun Saralees nadarajah Department of Statistics University of Mazandaran47416-1467BabolsarIran Department of Statistics Persian Gulf UniversityBushehr75169Iran Department of Statistics Bartin UniversityBartin 74100Turkey School of Mathematics University of ManchesterManchester M13 9PLUK

In this paper, we introduce a new extension of the power Lindley distribution, called the exponentiated generalized power Lindley distribution. Several mathematical properties of the new model such as the shapes of the density and hazard rate functions, the quantile function, moments, mean deviations, Bonferroni and Lorenz curves and order statistics are derived. Moreover, we discuss the parameter estimation of the new distribution using the maximum likelihood and diagonally weighted least squares methods. A simulation study is performed to evaluate the estimators. We use two real data sets to illustrate the applicability of the new model. Empirical findings show that the proposed model provides better fits than some other well-known extensions of Lindley distributions.

关键词： Anderson-Darling test statistic Exponentiated generalized class of distributions Lambert function Maximum likelihood method Power Lindley distribution

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