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New insights into estrogenic regulation of O^6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells： Co-degradation of ER-α and MGMT proteins by fulvestrant or O^6-benzylguanine indicates fresh avenues for therapy

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The Journal of Biomedical Research 2016年第5期30卷 393-410页

作者： Ameya Paranjpe Nathan I. Bailes Santhi Konduri George C. Bobustuc francis ali-osman Mohd. A. Yusuf Surendra R. Punganuru Hanumantha Rao Madal Debasish Basak AGM Mostofa Kalkunte S. Srivenugopa Department of Biomedical Sciences and Cancer Biology Center School of Pharmacy Texas Tech University Health Sciences Center Amarillo TX 79106 USA Neuro-Oncology Section Aurora Advanced Cancer Care Milwaukee WI 53215 USA Department of Surgery The Preston Robert Tisch Brain Tumor Center Duke University Durham NC 27710 USA

Endocrine therapy using estrogen receptor-u （ER-α） antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers. To exploit any DNA repair deficiencies associated with endocrine therapy, we investigated the functional and physical interactions of ER-α with O^6-methylguanine DNA methyltransferase （MGMT）, a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents. The ER-α -positive breast cancer cell lines （MCF-7, T47D） and ER- negative cell lines （MDAMB- 468, MDAMB-231）, and established inhibitors of ER-α and MGMT, namely, ICI-182,780 （Faslodex） and O^6- benzylguanine, respectively, were used to study MGMT- ER interactions. The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements （EREs） and two antioxidant-responsive elements （AREs）. MGMT expression was upregulated by estrogen, downregulated by tamoxifen in Western blot and promoter-linked reporter assays. Similarly, both transient and stable transfections of Nrf-2 （nuclear factor-erythroid 2-related factor-2） increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this dragresistance determinant. Of the different ER-α antagonists tested, the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose, time and ER-α dependent manner, similar to O^6-benzylguanine. Interestingly, fulvestrant exposure led to a degradation of both ER-α and MGMT proteins and O^6-benzylguanine also induced a specific loss of ER-a and MGMT proteins in MCF-7 and T47D breast cancer cells with similar kinetics. Immunoprecipitation revealed a specific association of ER-a and MGMT proteins in breast cancer cells. Furthermore, silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-a proteins. The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated. Fulvestrant enhanced th

关键词： estrogen signaling MGMT DNA repair ubiquitin-proteasome pathway breast cancer anti-estrogens

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Decoupling of DNA damage response signaling from DNA damages underlies temozolomide resistance in glioblastoma cells

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The Journal of Biomedical Research 2010年第6期24卷 424-435页

作者： Stewart P.Johnson Nancy Bullock francis ali osman Darell D.Bigner Henry S.Friedman Departments of Surgery Duke University Medical Center Departments of Pathology Duke University Medical Center

Glioblastoma multiforme （GBM） is the most aggressive primary brain tumor in *** therapy includes surgery,radiation and chemotherapy with temozolomide （TMZ）.Major determinants of clinical response to TMZ include methylation status of the O6-methylguanine-DNA methyltransferase （MGMT） promoter and mismatch repair （MMR） *** the MGMT promoter is methylated in 45% of cases,for the first nine months of follow-up,TMZ does not change survival ***,MMR deficiency makes little contribution to clinical resistance,suggesting that there exist unrecognized mechanisms of *** generated paired GBM cell lines whose resistance was attributed to neither MGMT nor *** show that,responding to TMZ,these cells exhibit a decoupling of DNA damage response （DDR） from ongoing DNA *** display methylation-resistant synthesis in which ongoing DNA synthesis is not *** are also defective in the activation of the S and G2 phase *** proteins ATM,Chk2,MDC1,NBS1 and gammaH2AX also fail to form discrete *** results demonstrate that failure of DDR may play an active role in chemoresistance to *** damages by TMZ are repaired by MMR proteins in a futile,reiterative process,which activates DDR signaling network that ultimately leads to the onset of cell *** cells may survive genetic insults in the absence of *** anticipate that our findings will lead to more studies that seek to further define the role of DDR in ultimately determining the fate of a tumor cell in response to TMZ and other DNA methylators.

关键词： glioblastomas multiforme temozolomide DNA damage response resistance

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The Case of the Carnian(Triassic) Conodont Genus Metapolygnathus Hayashi

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Journal of Earth Science 2015年第2期26卷 219-223页

作者： ali Murat Kili Pablo Plasencia Keisuke Ishida francis Hirsch Department of Geological Engineering Balikesir University Department of Geology and ICBIBE University of ValenciaDr. Moliner 50. 46100 Burjassot Spain Laboratory of Geology Faculty of Sciences Tokushima University Laboratory of Geology Faculty of Sciences Naruto University

Successive evolutionary trends control the genera Paragondolella Mosher and Meta- polygnathus Hayashi over the about 20 Ma long Aegean-Tuvalian timespan. In consideration of their evolutionary criteria, these genera have been retained together with Carnepigondolella Kozur and the two new genera proposed herein, MazzaeUa （type species M. carnica） and Hayashiella （type species H. nodosa）. Mazzaella n. gen. represents a Late Julian side branch ofMetapolygnathus, harbouring a platform ornamentation similar to the several million years younger Tuvalian lineage of Carnepigondolella, issued from Hayashiella n. gen. that is intermediary between Metapolygnathus and CarnepigondoleUa, based on appearance and platform ornamentation.

关键词： Carnian conodont phylogeny evolutionary trend.

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Limbal leproma in lepromatous leprosy

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International Journal of Ophthalmology(English edition) 2011年第6期4卷 678-681页

作者： Irimpan Lazar francis Nadir ali Mohamed ali Pemasiri Upali Telisinghe Nayan Joshi Department of Ophthalmology RIPAS Hospital Department of Pathology RIPAS Hospital

Dear Sir, W e are writing to you to present an unusual case of leproma growing at the limbus of a lepromatous leprosy patient. This the first report of ocular leprosy in Brunei, where leprosy is extremely rare. Leprosy, otherwise known as Hansen’s disease, is a chronic granulomatous communicable infection caused by Mycobacterium leprae and its genetic variant (Mycobacterium lepromatosis) [1]. A leproma is a superficial, ci

关键词： Limbal leproma in lepromatous leprosy oral Figure

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Patient care during interfacility transport:a narrative review of managing diverse disease states

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World Journal of Emergency Medicine 2023年第1期14卷 3-9页

作者： Quincy K.Tran francis O’Connell Andrew Hakopian Marwa SH Abrahim Kamilla Beisenova ali Pourmand Department of Emergency Medicine University of Maryland School of MedicineBaltimore 21201USA Program in Trauma the R Adams Cowley Shock Trauma CenterUniversity of Maryland School of MedicineBaltimore 21201USA Department of Emergency Medicine George Washington University School of Medicine and Health SciencesWashington DC 20037USA

BACKGROUND:When critically ill patients require specialized treatment that exceeds the capability of the index hospitals,patients are frequently transferred to a tertiary or quaternary hospital for a higher level of ***,appropriate and efficient care for patients during the process of transport between two hospitals(interfacility transfer)is an essential part of patient *** medical adverse events may occur during the interfacility transfer process,there have not been evidence-based guidelines regarding the equipment or the practice for patient care during ***:We conducted searches from the PubMed,Cumulative Index of Nursing and Allied Health(CINAHL),and Scopus databases up to June *** reviewers independently screened the titles and abstracts for *** that were not in the English language and did not involve critically ill patients were ***:The search identified 75 articles,and we included 48 studies for our narrative *** studies were observational ***:The review provided the current evidence-based management of diverse disease states during the interfacility transfer process,such as proning positioning for respiratory failure,extracorporeal membrane oxygenation(ECMO),obstetric emergencies,and hypertensive emergencies(aortic dissection and spontaneous intracranial hemorrhage).

关键词： Critically ill patients Interfacility transfer Interhospital transfer Extracorporeal membrane oxygenation Obstetric emergencies Hypertensive emergencies

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Interventions to improve sarcopenia in cirrhosis: A systematic review

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World Journal of Clinical Cases 2019年第2期7卷 156-170页

作者： Maliha Naseer Erica P Turse ali Syed francis E Dailey Mallak Zatreh Veysel Tahan Department of Internal Medicine Division of Gastroenterology and Hepatology East Carolina University Department of Internal Medicine Division of Gastroenterology St Joseph Hospital Medical Center/Creighton University Department of Internal Medicine University of Missouri Department of Internal Medicine Division of Gastroenterology and Hepatology University of Missouri

BACKGROUND Sarcopenia, i.e., muscle loss is now a well-recognized complication of cirrhosis and in cases of non-alcoholic fatty liver disease can contribute to accelerate liver fibrosis leading to cirrhosis. Hence, it is imperative to study interventions which targets to improve sarcopenia in *** To examine the relationship between interventions such nutritional supplementation, exercise, combined life style intervention, testosterone replacement and trans jugular intrahepatic portosystemic shunt(TIPS) to improve muscle mass in *** We search PubMed, EMBASE and Cochrane between June-August 2018, without a limiting period and the types of articles(RCTs, clinical trial, comparative study)in adult patients with sarcopenia and cirrhosis. The primary outcome of interest was improvement in muscle mass, strength and physical function interventions mentioned above. In the screening process, 154 full text articles were included in the review and 129 studies were *** We identified 24 studies that met review inclusion criteria. The studies were diverse in terms of the design, setting, interventions, and outcome *** performed only qualitative synthesis of evidence due to heterogeneity amongst studies. Risk of bias was medium in most of the included studies and low quality of evidence showed improvement in the muscle mass, strength and physical function following aerobic exercise. 60% of the included studies on the nutritional intervention, 100% of the studies on testosterone replacement in hypogonadal men and trans-jugular portosystemic shunt were proved to be effective in improving sarcopenia in *** Although the quality of evidence is low, the findings of our systematic review suggest improvement in the sarcopenia in cirrhosis with exercise, nutritional interventions, hormonal and TIPS interventions. High quality randomized controlled trials needed to further strengthen these findings.

关键词： Sarcopenia Cirrhosis Treatment Intervention Nutrition Therapy Exercise Testosterone Trans jugular intrahepatic portosystemic shunt

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Modelling and Characterization of Basalt/Vinyl Ester/SiC Micro-and Nano-hybrid Biocomposites Properties Using Novel ANN–GA Approach

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Journal of Bionic Engineering 2024年第2期21卷 938-952页

作者： Yesudhasan Thooyavan Lakshmi Annamali Kumaraswamidhas Robinson Dhas Edwin Raj Joseph Selvi Binoj Bright Brailson Mansingh Antony Sagai francis Britto Alamry ali Department of Mechanical Engineering Indian Institute of Technology Dhanbad(ISM)DhanbadJharkhand826004India Gati Shakti Vishwavidyalaya(GSV-A Central University Funded By GoI in the Ministry of Railways) LalbaugVadodaraGujarat390004India Institute of Mechanical Engineering Saveetha School of EngineeringSaveetha Institute of Medical and Technical Sciences(SIMATS)Saveetha UniversityChennaiTamilnadu602105India Metal Joining Research Centre Department of Mechanical EngineeringSri Ramakrishna Engineering CollegeCoimbatoreTamilnadu641022India Department of Mechanical Engineering Rohini College of Engineering and TechnologyPalkulamTamil Nadu629401India Department of Mechanical Engineering College of Engineering in Al-KharjPrince Sattam Bin Abdulaziz University11942Al-KharjSaudi Arabia

Basalt fiber reinforcement in polymer matrix composites is becoming more and more popular because of its environmental friendliness and mechanical qualities that are comparable to those of synthetic *** fiber strengthened vinyl ester matrix polymeric composite with filler addition of nano-and micro-sized silicon carbide(SiC)element spanning from 2 weight percent to 10 weight percent was studied for its mechanical and wear *** application of Artificial Neural Network(ANN)to correlate the filler addition composition for optimum mechanical properties is required due to the non-linear mechanical and tribological features of *** stuffing blend and composition of the composite are optimized using the hybrid model and Genetic Algorithm(GA)to maximize the mechanical and wear-resistant *** predicted and tested ANN–GA optimal values obtained for the composite combination had a tensile,flexural,impact resilience,hardness and wear properties of 202.93 MPa,501.67 MPa,3.460 J/s,43 HV and 0.196 g,respectively,for its optimum combination of filler and *** can be noted that the nano-sized SiC filler particle enhances most of the properties of the composite which diversifies its *** predicted mechanical and wear values of the developed ANN–GA model were in closer agreement with the experimental values which validate the model.

关键词： Hybrid polymer composite Prediction Process modelling Artificial neural networks Genetic algorithm

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Adsorptive removal and catalytic performance of metal-organic frameworks containing mixed azolium-bipyridine ligand

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Resources Chemicals and Materials 2022年第3期1卷 201-210页

作者： Nadia Gholampour Chizoba I.Ezugwu Shima Rahmdele ali Ghanadzadeh Gilanie francis Verpoort State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Department of Chemical Engineering University of AlcaláE-28871 Alcaláde HenaresMadridSpain Department of Chemistry Faculty of ScienceUniversity of GuilanRashtIran National Research Tomsk Polytechnic University Lenin Avenue 30634050 TomskRussian Federation Institute of Condensed Matter and Nanosciences Universit..catholique de LouvainPlace Louis Pasteur1348 Louvain-la-NeuveBelgium

Two ligands, 1, 3-bis(4-carboxyphenyl)imidazolium chloride and 4, 4-bipyridine, were employed to prepare nickel and zinc azolium based MOFs, Ni-MOF and Zn-MOF by the mixed ligand solvothermal approach. The positively charged azolium moieties in the imidazolium linker resulted in a charged environment in the as-synthesized frameworks. As a result, Ni-MOF and Zn-MOF demonstrated preferential adsorption of CO_(2) over methane molecules in the gas phase adsorption due to the higher quadruple moment of CO_(2), which interacts more with the positively charged frameworks. Besides, in aqueous media, Ni-MOF and Zn-MOF exhibited incredible adsorption efficiency for anionic dyes. In the following, Ni-MOF was metallated at the carbene site of the azolium linker to generate the novel heterogeneous catalyst Pd/Ni-MOF, which was successfully applied for Sonogashira and Suzuki-Miyaura coupling reactions without losing its activity after three cycles.

关键词： Azolium MOFs Dye adsorption Post modification Cross-coupling reactions

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Fuzzy Difference Equations in Diagnoses of Glaucoma from Retinal Images Using Deep Learning

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Computer Modeling in Engineering & Sciences 2024年第4期139卷 801-816页

作者： D.Dorathy Prema Kavitha L.francis Raj Sandeep Kautish Abdulaziz S.Almazyad Karam M.Sallam ali Wagdy Mohamed Department of Mathematics Voorhees CollegeVelloreTamil NaduIndia Chandigarh Group of Colleges JhanjeriMohaliPunjabIndia Department of Computer Engineering College of Computer and Information SciencesKing Saud UniversityP.O.Box 51178Riyadh11543Saudi Arabia Faculty of Science and Technology School of IT and SystemsUniversity of CanberraCanberraAustralia Operations Research Department Faculty of Graduate Studies for Statistical ResearchCairo UniversityGiza12613Egypt Applied Science Research Center Applied Science Private UniversityAmman11937Jordan

The intuitive fuzzy set has found important application in decision-making and machine *** enrich and utilize the intuitive fuzzy set,this study designed and developed a deep neural network-based glaucoma eye detection using fuzzy difference equations in the domain where the retinal images *** image detections are categorized as normal eye recognition,suspected glaucomatous eye recognition,and glaucomatous eye *** degrees associated with weighted values are calculated to determine the level of concentration between the fuzzy partition and the retinal *** proposed model was used to diagnose glaucoma using retinal images and involved utilizing the Convolutional Neural Network(CNN)and deep learning to identify the fuzzy weighted regularization between *** methodology was used to clarify the input images and make them adequate for the process of glaucoma *** objective of this study was to propose a novel approach to the early diagnosis of glaucoma using the Fuzzy Expert System(FES)and Fuzzy differential equation(FDE).The intensities of the different regions in the images and their respective peak levels were *** the peak regions were identified,the recurrence relationships among those peaks were then *** partitioning was done due to varying degrees of similar and dissimilar concentrations in the *** and dissimilar concentration levels and spatial frequency generated a threshold image from the combined fuzzy matrix and *** distinguished between a normal and abnormal eye condition,thus detecting patients with glaucomatous eyes.

关键词： Convolutional Neural Network(CNN) glaucomatous eyes fuzzy difference equation intuitive fuzzy sets image segmentation retinal images

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Detection of Different Stages of Alzheimer’s Disease Using CNN Classifier

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Computers, Materials & Continua 2023年第9期76卷 3933-3948页

作者： S M Hasan Mahmud Md Mamun ali Mohammad Fahim Shahriar Fahad Ahmed Al-Zahrani Kawsar Ahmed Dip Nandi francis M.Bui Department of Computer Science American International University-Bangladesh(AIUB)Dhaka1229Bangladesh Centre for Advanced Machine Learning and Applications(CAMLAs) DhakaBangladesh Department of Software Engineering Daffodil International UniversityDhakaBangladesh Department of Computer Engineering Umm Al-Qura UniversityMecca24381Saudi Arabia Department of ECE University of SaskatchewanSaskatoonSK S7N5A9Canada Group of Biophotomatiχ Department of ICTMBSTUSantoshTangail1902Bangladesh

Alzheimer’s disease(AD)is a neurodevelopmental impairment that results in a person’s behavior,thinking,and memory *** common symptoms ofADare losingmemory and early *** addition to these,there are several serious impacts ***,the impact ofADcanbemitigatedby early-stagedetection though it cannot be cured ***-stage detection is the most challenging task for controlling and mitigating the impact of *** study proposes a predictive model to detect AD in the initial phase based on machine learning and a deep learning approach to address the *** build a predictive model,open-source data was collected where five stages of images of AD were available as Cognitive Normal(CN),Early Mild Cognitive Impairment(EMCI),Mild Cognitive Impairment(MCI),Late Mild Cognitive Impairment(LMCI),and *** stage of AD is considered as a class,and then the dataset was divided into three parts binary class,three class,and five *** this research,we applied different preprocessing steps with augmentation techniques to efficiently *** integrates a random oversampling technique to handle the imbalance problem from target classes,mitigating the model overfitting and *** three machine learning classifiers,such as random forest(RF),K-Nearest neighbor(KNN),and support vector machine(SVM),and two deep learning methods,such as convolutional neuronal network(CNN)and artificial neural network(ANN)were applied on these *** analyzing the performance of the used models and the datasets,it is found that CNN with binary class outperformed 88.20%*** result of the study indicates that the model is highly potential to detect AD in the initial phase.

关键词： Alzheimer’s disease early detection convolutional neural network data augmentation random oversampling machine learning

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