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Expression of c-kit receptor in human cholangiocarcinoma and in vivo treatment with imatinib mesilate in chimeric mice

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World Journal of Gastroenterology 2006年第10期12卷 1583-1590页

作者： Thomas Kamenz Karel Caca Thilo Blüthner Andrea Tannapfel Joachim Mssner marcus Wiedmann Department of Internal Medicine Ⅱ University of Leipzig Philipp-Rosenthal-Str.2704103 LeipzigGermany Institute of Pathology University of Leipzig Liebigstr.2604103 LeipzigGermany

AIM： To investigate the c-kit expression in biliary tract cancer cell lines and histological sections from patients with extrahepatic cholangiocarcinoma （CC） and to evaluate the efficacy of in vitro and in vitro treatment with imatinib mesilate. METHODS： The protein expression of c-kit in the human biliary tract cancer cell lines Mz-ChA-2 and EGI-1 and histological sections from 19 patients with extrahepatic CC was assessed by immunoblotting, immunocytochemistry, and immunohistochemistry. The anti-proliferative effect of imatinib mesilate on biliary tract cancer cell lines Mz-ChA-2 and EGI-1 was studied in vitro by automated cell counting. In addition, immunodeficient NMRI mice （Taconic^TM） were subcutaneously injected with 5 × 10^6 cells of cell lines MzChA-2 and EGI-1. After having reached a tumour volume of 200 mm^3, daily treatment was started intraperitoneally with imatinib mesilate at a dose of 50 mgikg or normal saline （NS）. Tumor volume was calculated with a Vernier caliper. After 14 d, mice were sacrificed with tumors excised and tumor mass determined.RESULTS： Immunoblotting revealed presence of c-kit in Mz-ChA-2 and absence in EGI-1 cells. Immunocytochemistry with c-kit antibodies displayed a cytoplasmatic and membraneous localization of receptor protein in Mz-ChA-2 cells and absence of c-kit in EGI-1 cells, c-kit was expressed in 7 of 19 （37%） extrahepatic humanCC tissue samples, 2 showed a moderate and 5 a rather weak immunostaining. Imatinib mesilate at a low concentration of 5 μmoliL caused a significant growth inhibition in the c-kit positive cell line Mz-ChA-2 （31%）, but not in the c-kit negative cell line EGI-1 （0%）（P〈0.05）. Imatinib mesilate at an intermediate concentration of 10 μmoliL inhibited cellular growth of both cell lines （51% vs 57%）. Imatinib mesilate at a higher concentration of 20 μmoliL seemed to have a general toxic effect on both cell lines. The IC50 values were 9.7 μmoliL and 11 μmoliL, respectively. After 14 d of in vitro treat

关键词： Cholangiocarcinoma Imatinib Tyrosine kinase inhibitor c-kit Chimeric mice

Deep reinforcement learning for home energy management system control

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能源与人工智能(英文) 2021年第1期3卷 64-72页

作者： Paulo Lissa Conor Deane Michael Schukat federico Seri marcus Keane Enda Barrett College of Science and Engineering National University of IrelandGalwayIreland Informatics Research Unit for Sustainable Engineering(IRUSE)Galway Ireland Ryan Institute National University of Ireland GalwayIreland

The use of machine learning techniques has been proven to be a viable solution for smart home energy *** techniques autonomously control heating and domestic hot water systems,which are the most relevant loads in a dwelling,helping consumers to reduce energy consumption and also improving their ***,the number of houses equipped with renewable energy resources is increasing,and this is a key ele-ment for energy usage optimization,where coordinating loads and production can bring additional savings and reduce peak *** this regard,we propose the development of a deep reinforcement learning(DRL)algorithm for indoor and domestic hot water temperature control,aiming to reduce energy consumption by optimizing the usage of PV energy ***,a methodology for a new dynamic indoor temperature setpoint definition is presented,thus allowing greater flexibility and *** results show that the proposed DRL al-gorithm combined with the dynamic setpoint achieved on average 8%of energy savings compared to a rule-based algorithm,reaching up to 16%of savings over the summer ***,the users’comfort has not been compromised,as the algorithm is calibrated to not exceed more than 1%of the time out the specified temperature *** analysis shows that further savings could be achieved if the time out of comfort is increased,which could be agreed according to users’*** demand side management,the DRL control shows efficiency by anticipating and delaying actions for a PV self-consumption optimization,performing over 10%of load ***,the renewable energy consumption is 9.5%higher for the DRL-based model compared to the rule-based,which means less energy consumed from the grid.

关键词： Deep reinforcement learning Residential home energy management Demand response Autonomous control

Immune cells in term and preterm labor

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Cellular & Molecular Immunology 2014年第6期11卷 571-581页

作者： Nardhy Gomez-Lopez Derek StLouis marcus A Lehr Elly N Sanchez-Rodriguez Marcia Arenas-Hernandez Department of Obstetrics & Gynecology and Immunology & Microbiology Wayne State University Detroit MI USA Perinatology Research Branch NICHD/NIH School of Medicine Wayne State University Detroit MI USA

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells （neutrophils, macrophages and mast cells） mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells （T-cell subsets and B cells） participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems （natural killer T （NKT） cells and dendritic cells （DCs）） seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm.

关键词： B cells cytotoxic T cells dendritic cells macrophages mast cells neutrophils NKT cells parturition preterm delivery regulatory T cells T cells

Characterization of the acidity and basicity of green solvents by NMR techniques

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Magnetic Resonance Letters 2021年第1期1卷 81-88页

作者： Kemeng Shi Christian marcus Pedersen Hui Chang Jing Shi Yingxiong Wang Yan Qiao Institute of Coal Chemistry Chinese Academy of SciencesTaiyuan030001China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing100049China Department of Chemistry University of CopenhagenDK-2100 CopenhagenDenmark Sinopec Shanghai Petrochemical Co. Ltd.Shanghai200540China

The acidity and basicity of the solvents can influence the reaction outcome notably,and hence the precise measurement of pH is important for ***,not all the pH values of organic solvents can be determined with a classic pH meter *** this research,the acidity and basicity of environmentally friendly green solvents,such as ZnCl_(2) molten salt hydrate,ionic liquids(ILs)and deep eutectic solvents(DESs),were characterized by 31P and 1 H NMR spectroscopy using trimethylphosphine oxide(TMPO)and pyrrole as probe molecules at 298 *** the ZnCl_(2) molten salt hydrate,the acidic strength of the ZnCl_(2) molten salt hydrate increased with the concentration of ZnCl_(2).By using the ^(1)H-pyrrole NMR approach,it was found that the base strength of amino acid-based ILs follows the order:[Ch][Lys]>[Ch][His].

关键词： Green solvents Acidity Basicity ^(31)P-TMPO NMR ^(1)H-pyrrole NMR

Towards a Wireless Sensor Platform for Energy Efficient Building Operation

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Tsinghua Science and Technology 2008年第S1期13卷 381-386页

作者： Karsten Menzel Dirk Pesch Brendan O'flynn marcus Keane Cian O'Mathuna University College Cork Cork Institute of Technology Tyndall National Institute National University of Ireland

Currently, the IT-support for energy performance rating of buildings is insufficient. So-called IT-platforms often 'built' of an ad-hoc, inconsistent combination of off-the-shelf building management compo-nents, distributed data metering equipment and several monitoring software tools. A promising approach to achieve consistent, holistic performance data management is the implementation of an integrated, modular wireless sensor platform. This paper presents an approach of how wireless sensors can be seamlessly integrated into existing and future intelligent building management systems supporting improved building performance and diagnostics with an emphasis on energy management.

关键词： computer-based monitoring and maintenance of infrastructure wireless sensor platform energy efficient building

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care

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World Journal of Gastroenterology 2020年第18期26卷 2221-2231页

作者： Anuj Bohra Thomas Worland Samuel Hui Ryma Terbah Ann farrell marcus Robertson Department of Gastroenterology Monash HealthClayton 3168VictoriaAustralia Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of Medicine School of Clinical SciencesMonash UniversityClayton 3168VictoriaAustralia

BACKGROUND Hepatic encephalopathy(HE)is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50%of cirrhotic *** examining the prognostic significance of HE are limited despite the high prevalence in *** To define the clinical outcomes of patients after an episode of HE treated with current *** All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over46-mo(2012–2016)were identified via pharmacy dispensing *** with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were *** records were reviewed to determine baseline characteristics and *** Kaplan-Meier method was used to calculate survival *** survival analysis was performed with variables reaching statistical significance included in a multivariate *** primary outcome was 12-mo mortality following commencement of ***188 patients were *** age was 57 years(IQR 50-65),71%were male and median model for end stage liver disease and Child Pugh scores were 25(IQR 18-31)and 11(IQR 9-12)*** most common causes of cirrhosis were alcohol(62%),hepatitis C(31%)and non-alcoholic fatty liver disease(20%).A precipitating cause for HE was found in 92%patients with infection(43%),GI bleeding(16%),medication non-compliance(15%)and electrolyte imbalance(14%)the most *** a mean follow up period of 12±13 mo 107(57%)patients died and 32(17%)received orthotopic liver *** common causes of death were decompensated chronic liver disease(57%)and sepsis(19%).The probability of survival was 44%and 35%at 12-and 24-mo *** multivariate analysis a model for end stage liver disease>15 and international normalised ratio reached statistical significance in predicting *** Despite advances made in the management of HE patients continue to have poor ***,in all patients

关键词： Hepatic encephalopathy Cirrhosis Portal hypertension Prognosis Rifaximin Lactulose

The Impact of Tournament Load on Neuromuscular function, Perceived Wellness and Coach Ratings of Performance During Intensified Youth Netball Competition

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Journal of Science in Sport and Exercise 2023年第1期5卷 16-24页

作者： marcus Lee Jericho Wee Nick Dobbin Quintin Roman Gabriel Choong Sport Science National Youth Sports InstituteSingaporeSingapore Department of Health Professions Manchester Metropolitan UniversityManchesterUK Human Potential Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Performance Pathway National Youth Sports InstituteSingaporeSingapore

Purpose This study examined the effects of tournament load on neuromuscular function,perceived wellness and coach rat-ings of performance across two 6-day netball *** Thirty-nine female youth netballers(age=14.6±0.5 years,stature=165.9±4.7 cm,body mass=56.5±7.2 kg)were categorised as HIGH(10-11 matches,n=20)or LOW(6 matches,n=19)tournament *** load,jump height,perceived wellness and coach ratings of performance were monitored *** HIGH tournament load resulted in greater reductions in jump height on match-day 4(-8.3%,±5.6%)when compared to *** tournament load resulted in greater reductions in perceived soreness(-0.9,±1.1 AU)and overall wellness(-2.6,±2.3 AU)on match-day 3,and a greater reduction in perceived sleep(-0.9,±1.1 AU)on match-day *** tournament load was negatively associated with sleep quality and coach ratings of performance(effect size correlation=-0.34 to-0.47)when compared to *** Our results indicate that a higher tournament load resulted in greater increases in neuromuscular fatigue,reduced perceived wellness,and lower ratings of *** should consider pre-tournament preparation and monitoring strategies to minimise the physiological disturbances during an intensified tournament.

关键词： Netball Monitoring Post-match fatigue Youth tournament Tournament structure

LKB1 tumor suppressor: Therapeutic opportunities knock when LKB1 is inactivated

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Genes & Diseases 2014年第1期1卷 64-74页

作者： Wei Zhou Jun Zhang Adam I.marcus Department of Hematology and Medical Oncology The Winship Cancer InstituteEmory University School of MedicineAtlantaGeorgia

LKB1 is commonly thought of as a tumor suppressor gene because its hereditary mutation is responsible for a cancer syndrome,and somatic inactivation of LKB1 is found in nonsmall cell lung cancer,melanoma,and cervical ***,unlike other tumor suppressors whose main function is to either suppress cell proliferation or promote cell death,one of the functions of LKB1-regulated AMPK signaling is to suppress cell proliferation in order to promote cell survival under energetic stress *** unique,pro-survival function of LKB1 has led to the discovery of reagents,such as phenformin,that specifically exploit the vulnerability of LKB1-null cells in their defect in sensing energetic *** targeted agents represent a novel treatment strategy because they induce cell killing when LKB1 is *** review article summarizes various vulnerabilities of LKB1-mutant cells that have been reported in the literature and discusses the potential of using existing or developing novel reagents to target cancer cells with defective LKB1.

关键词： Metabolic stress Targeted therapy Tumor Suppressor Tumor vulnerability

Delay Times and Clinical Outcomes in Acute Myocardial Infarction: Comparison of Periods before and during the COVID-19 Pandemic—Myocardial Infarction and the Pandemic

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World Journal of Cardiovascular Diseases 2024年第6期14卷 392-400页

作者： Clarice Teixeira Silva Araújo Arnon Salviato Mameri Thúlio Carrera Guarçoni Venturini marcus Tadeu Aguilar Constantino Matos Igor Morais Araujo Lopes Luiz Gustavo Ribeiro de Carvalho Murad Cleberson Duartes Ovani Guilherme Vassalo Morais fernanda Venturini de Castro Danielle Lopes Rocha Lucas Crespo de Barros Rodolfo Costa Sylvestre Luiz fernando Machado Barbosa Roberto Ramos Barbosa Internal Medicine Universidade Federal do Esprito Santo (UFES) Vitria Brazil Hospital Santa Casa de Misericrdia de Vitria Vitria Brazil Hospital Santa Rita de Cssia Vitria Brazil Hospital Estadual Dr. Jayme Santos Neves Serra Brazil Grupo Kora Sade Vitria Brazil Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIMABA) Vila Velha Brazil

Introduction: At the beginning of the COVID-19 pandemic, a drop in the number of patients treated for cardiac emergencies raised concern about cardiovascular mortality in that period. An increase in care delay for patients with ST-segment elevation myocardial infarction (STEMI) may have affected clinical outcomes. Objectives: To analyze delay times and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI), before and during the COVID-19 pandemic. Methods: Retrospective observational study that included patients with STEMI undergoing PPCI from December 2018 to July 2021. The COVID-19 pandemic cases were divided into two groups: pandemic I—from March to August 2020;and pandemic II—from September 2020 to July 2021. Patients were compared according to the period of hospitalization. Primary outcomes were delay times in assistance and clinical outcomes (acute kidney injury [AKI], post-procedural vascular complications and in-hospital mortality). Results: 108 patients were included, 39 (36.1%) in the pre-pandemic period, 13 (12.1%) in pandemic I and 56 (51.8%) in pandemic II. Time from onset of symptoms to arrival at the service and door-to-balloon time did not differ significantly among groups. Vascular complications were more frequent during the pandemic (I and II) than in the pre-pandemic period (2.5% pre-pandemic vs 15.4% pandemic vs 12.5% pandemic II;p = 0.03). AKI incidence was similar in all three periods. There was a non-significant increase in in-hospital mortality during the COVID-19 pandemic. Conclusion: In patients with STEMI, there was an increase in vascular complications and a trend toward increased mortality during the COVID-19 pandemic. Delay times to admission and reperfusion did not differ significantly between before and during the pandemic.

关键词： Myocardial Infarction Primary Percutaneous Coronary Intervention Coronary Reperfusion Pandemic COVID-19