|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation显示文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation. | David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni Cristina Alonso María Luz Martínez-Chantar Felix Elortza Liat Hayardeny Shelly C Lu JoséM Mato | 2020 | World Journal of Gastroenterology2020，26，34： | 5 |
| 2 | Real-time calculation of fragment velocity for cylindrical warheads显示文摘To simulate explosion fragments, it is necessary to predict many variables such as fragment velocity, size distribution and projection angle. For active protection systems these predictions need to be made very quickly, before the weapon hits the target. Fast predictions also need to be made in real time simulations when the impact of many different computer models need to be assessed. The research presented in this paper focuses on creating a fast and accurate estimate of one of these variables - the initial fragment velocity. The Gurney equation was the first equation to calculate initial fragment velocity. This equation, sometimes with modifications, is still used today where finite element analysis or complex mathematical approaches are considered too computationally expensive. This paper enhances and improves Breech’s two-dimensional Gurney equation using available empirical data and the principals of conservation of momentum and energy. The results are computationally quick, providing improved accuracy for estimating initial fragment velocity. This will allow the developed model to be available for real-time simulation and fast computation, with improved accuracy when compared to existing approaches. | David Felix Ian Colwill Elias Stipidis | 2019 | Defence Technology(防务技术)2019，15，3： | 4 |
| 3 | Seasonal variation for the antidiabetic activity of Loranthus micranthus methanol extract显示文摘Objective:To determine the season in which the Eastern Nigeria mistletoe,Loranthus micranthus,parasitic on Persea americana possesses optimum antidiabetic activity and to determine the seasonal variation in the constituents.Methods:The antidiabetic activities of the aqueous methanol extracts of the leaves of Eastern Nigeria mistletoe,Loranthus micranthus, harvested in two seasons of the year,the onset of rainy season(April) and the peak of rainy season(July) were compared.The tests were carried out on six(6) groups(A-F) of alloxaninduced diabetic rats.Groups A and B received 200 mg/kg and 400 mg/kg of the April sample extracts respectively while groups C and D received same doses of the July sample extracts. Group E and F which were the positive and negative controls received 10 mg/kg of glibenclamide and 2 ml/kg of 3%tween 20 respectively.The blood glucose levels of the animals were monitored hourly with a glucometer for six hours.The phytochemical analysis of the plant extracts were also carried out by standard procedures.Results:The results showed that group A and B exhibited significant(P<0.05) percentage reduction in the fasting blood sugar(FBS) level of the animals(38.9%and 39.2%respectively) with maximum reduction observed at the 5th and 6th hour respectively compared to glibenclamide(71.3%).Group C showed no significant (P>0.05) FBS reduction(15.9%) while group D exhibited highly significant(P<0.01) reduction (47.5%) with the maximum reduction occurring after 6 hours.The phytochemical analysis of the crude methanol extracts revealed the presence of carbohydrates,glycosides,saponins, tannins,flavonoids,steroids,terpenoids,acidic compounds,resins and oils.These were present in different proportions in both seasons.Conclusions:This study shows that there is a seasonal, dose-dependent variation in the chemical composition viz-a-viz the antidiabetic activity of the plant under study.This activity is highest at the peak of the rainy season. | Patience Ogoamaka Osadebe Edwin Ogechukwu Omeje Philip Felix Uzor Ernest Kenechukwu David Damian Chiedozie Obiorah | 2010 | Asian Pacific Journal of Tropical Medicine2010，3，3： | 4 |
| 4 | 成人IDH野生型星形细胞瘤从生物学和临床上归为其他肿瘤类型显示文摘WHO III级的IDH野生型间变性星形细胞瘤预后差。为了对星形细胞瘤进行分子亚组分型或诊断上的重新分类,作者分析160例成人IDH野生型星形细胞肿瘤的分子标志性变异,并行甲基化和拷贝数分析,其中包括120例 WHO III级的间变性星形细胞瘤和40例WHO II级的弥漫型星形细胞瘤。基于分子谱系和标志性变异特征,将这些肿瘤分为四个主要亚型。78%肿瘤诊断为传统胶质母细胞瘤分子亚型。9%为GBM-H3F3A突变(GBM-H3)亚型。8%具有独特的甲基化特征,与GBM-H3-K27相似,但缺乏H3F3A突变,这组肿瘤主要发生在幕下及中线部位,并且预后较好。120例IDH野生型的间变性星形细胞瘤除1例外均可归入上述3种亚型中。40例WHO II级的弥漫型星形细胞瘤中7例具有不同的分子特征,其中6例重新归类为其他不同的低级别肿瘤类型。有趣的是,TERT突变只发生在分子亚型的GBM (78%),且预后不良。 GBM-H3组缺乏 TERT突变,然而其预后更差。 | David E R Annekathrin K Felix S 李晓玲 王行富 | 2015 | 临床与实验病理学杂志2015，31，9： | 4 |
| 5 | Antidiabetic principles of Loranthus micranthus Linn.parasitic on Persea americana显示文摘Objective:To explore antidiabetic principles of the Eastern Nigeria mistletoe,Loranlhus micranthus Linn,parasitic on Persea Americana.Methods:The weakly acidic fraction of the aqueous methanol extract of the leaves of Loranlhus micranthus(Linn.) was isolated and tested for its antidiabetic activities.The isolation of the weakly acidic fraction was carried out following established physico-chemical based procedures.Furthermore,alloxan-induced diabetic rats were treated intraperitoneally(ip) with 250 mg/kg and 400 mg/kg of the weakly acidic fraction, glibenclamide 10 mg/kg(positive control) and 2 mg/kg of 3%v/v tween 20(negative control).The sugar levels of the treated and untreated animals were determined by withdrawing the blood at regular intervals and testing them with an automated glucometer.The phytochemical analysis of the acidic fraction was carried out using standard procedures.Chromatographic techniques were employed in the subsequent isolation and purification of the constituents of the weakly acidic fraction.Results:It was shown that the maximum effect of the weakly acidic fraction was obtained at 24 hours after administration and was found to be statistically comparable with that of the positive control.The phytochemical analysis revealed the presence of steroids,terpenoids, alkaloids,flavonoids,glycosides,carbohydrates,saponins,and acidic compounds in the crude extract and carbohydrates,flavonoids.terpenoids and oil in the weakly acidic fraction.Further purification of the weakly acidic fraction of the methanol extract using thin layer chromatography shows that toluene:methanol:diethyl amine(3:1:1) and chloroform:methanol:diethyl amine (9:1:1) are the best solvent system for the isolation of the various components of the weakly acidic fraction of the crude methanol extract of Loranlhus micranthus.Conclusions:The present study has led to the conclusion that the weakly acidic fraction of the plant under study has the potent antidiabetic activity and that the various components can be isolated using basic chromatographic techniques. | Patience Ogoamaka Osadebe Edwin Ogechukwu Omeje Sylvester Chukwuemeka Nworu Charles Okechukwu Esimone Philip Felix Uzor Ernest kenechukwu David John Uchechukwu Uzoma | 2010 | Asian Pacific Journal of Tropical Medicine2010，3，8： | 4 |
| 6 | In-situ investigation on real-time suspended sediment measurement techniques:Turbidimetry, acoustic attenuation,laser diffraction (LISST) and vibrating tube densimetry显示文摘Real-time measurements of Suspended Sediment mass Concentration(SSC) and Particle Size Distribution(PSD) are of prime importance for the investigation and management of fine-sediment related processes in surface water systems and hydraulic schemes. In a field study at the waterway of the hydropower plant(HPP) Fieschertal in the Swiss Alps, the real-time measurement performance of the following techniques and instruments were assessed based on measurements in the sediment seasons of the years 2013 and 2014:(1) turbidimetry,(2) single-frequency acoustic attenuation using a standard acoustic discharge measurement(ADM) installation,(3) laser diffraction(Laser In-Situ Scattering and Transmissometry, LISST), and(4) vibrating tube densimetry using a Coriolis Flow and Density Meter(CFDM).Reference SSCs were obtained from gravimetric analysis of 219 automatically pumped water samples.LISST additionally supplied PSD every minute. The median particle diameter, d_(50), was usually 15μm and increased occasionally to 100μm. The turbidimeter and the ADM underestimated the SSC when the transported particles were coarser than usual. Such temporary biases resulted from the poor correlation between d_(50) and SSC at this study site. The SSCs from CFDM and LISST were not or less biased by PSD variations. Mainly due to angular and flaky particle shapes, SSC from LISST needed a correction by 79% on average. With the usually prevailing silt particles, an optical path length of 5 mm and no dilution, the SSC measurement range of LISST was limited to about 1.5 g/l. The CFDM allowed measuring higher SSC than the other investigated instruments(e.g. up to 13.5 g/l). With a periodic offset correction, its relative SSC measurement uncertainty was < 20% for SSC≥ 1.5 g/I. To reliably measure a wide range of SSC with temporarily variable PSD, a combination of instruments is recommended: e.g. a standard LISST, a CFDM,and an automatic water sampler for gravimetric reference measurements. | David Felix Ismail Albayrak Robert Michael Boes | 2018 | International Journal of Sediment Research2018，33，1： | 3 |
| 7 | Effect of Steatohepatitis Associated with Irinotecan or Oxaliplatin Pretreatment on Resectability of Hepatic Colorectal Metastases显示文摘 | Felix G. Fernandez John Ritter J. Wendell Goodwin David C. Linehan William G. Hawkins Steven M. Strasberg | 2005 | Journal of the American College of Surgeons2005，，6： | 2 |
| 8 | A fast and accurate model for the creation of explosion fragments with improved fragment shape and dimensions显示文摘Explosion models based on Finite Element Analysis(FEA)can be used to simulate how a warhead fragments.However their execution times are extensive.Active protection systems need to make very fast predictions,before a fast attacking weapon hits the target.Fast execution times are also needed in real time simulations where the impact of many different computer models is being assessed.Hence,FEA explosion models are not appropriate for these real-time systems.The research presented in this paper delivers a fast simulation model based on Mott’s equation that calculates the number and weight of fragments created by an explosion.In addition,the size and shape of fragments,unavailable in Mott’s equation,are calculated using photographic evidence and a distribution of a fragment’s length to its width.The model also identifies the origin of fragments on the warhead’s casing.The results are verified against experimental data and a fast execution time is achieved using uncomplicated simulation steps.The developed model then can be made available for real-time simulation and fast computation. | David Felix Ian Colwill Paul Harris | 2022 | Defence Technology(防务技术)2022，18，2： | 2 |
| 9 | Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial显示文摘 | Benjamin M Scirica Marc P Bonaca Eugene Braunwald Gaetano M De Ferrari Daniel Isaza Basil S Lewis Felix Mehrhof Piera A Merlini Sabina A Murphy Marc S Sabatine Michal Tendera Frans Van de Werf Robert Wilcox David A Morrow | 2012 | The Lancet . 2012 (9850)2012，，9850： | 1 |
| 10 | Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors显示文摘 | Edward Sausville Patricia LoRusso Michael Carducci Judith Carter Mary F. Quinn Lisa Malburg Nilofer Azad David Cosgrove Richard Knight Peter Barker Sonya Zabludoff Felix Agbo Patricia Oakes Adrian Senderowicz | 2014 | Cancer Chemotherapy and Pharmacology2014，，3： | 1 |
| 11 | Interleukin-17 Signaling in Inflammatory, Kupffer Cells, and Hepatic Stellate Cells Exacerbates Liver Fibrosis in Mice显示文摘 | Fanli Meng Kai Wang Tomonori Aoyama Sergei I. Grivennikov YongHan Paik David Scholten Min Cong Keiko Iwaisako Xiao Liu Mingjun Zhang Christoph H. ?sterreicher Felix Stickel Klaus Ley David A. Brenner Tatiana Kisseleva | 2012 | Gastroenterology2012，，3： | 1 |
| 12 | Enforceable security policies revisited 显示文摘 | David B Vincent J Felix K | 2013 | ACM Transactions on Information and System Se- curity2013，16，1： | 1 |
| 13 | Challenge of Swiss Arbitral Awards- se- lected Statistical Data as 2013显示文摘 | FELIX D DAVID R | 2014 | ASA Bulletin2014，，32： | 1 |
| 14 | Effectiveness of the Swiss Agri-Environment Scheme in Promoting Biodiversity显示文摘 | EVA K DAVID K FELIX H | 2006 | Journal of Applied Ecology2006，43，1： | 1 |
| 15 | Assessment of the Effect of Hydrolysed Starch Graft Copolymers Application on Soil Nutrient (Phosphorus and Nitrogen) Retention显示文摘The effects of the application of the graft copolymers (Hydrolyzed starch-g-polyacrylonitrile (HSPAN) and Hydrolyzed starch-g-polyacrylic acid (HSPAA)) on the nitrogen (N) and phosphorus (P) retention capacity of soil was evaluated in this study. Soil nutrient (N and P) retention capacity tests was carried out at three graft copolymers application rates (3.0, 6.0, and 9.0g/kg soil) against a blank soil sample to which graft copolymers was not applied. Diammonium phosphate (DAP) at 0, 100, and 200mg in aqueous solution/kg soil were applied in triplicates. The soil samples were mixed thoroughly and allowed to air-dry. The residual N and P contents of the soil samples were determined and reported as the amounts of nutrients retained as a function of the graft copolymer and DAP application rates. The result of this study has clearly demonstrated the potential of the graft copolymers to alleviate problems related to nutrient loss from the soil media. Leaching of nutrients (N and P) in soil has been found to be reduced to minimal (0.46%N, and 1.13%P) with the application of hydrolyzed graft copolymer and the nutrients are thus available to plant for growth by suction pressure difference. | Lawrence O.Ekebafe David E.Ogbeifun Felix E.Okieimen Osazoduwa M.Ekebafe | 2018 | Materials Science(Materials Review)2018，2，1： | 1 |
| 16 | Pesticide Use and Mycotoxin Production in Fusarium and Aspergillus Phytopathogens显示文摘 | J.P. Felix D’Mello Ann M.C. Macdonald David Postel Wilko T.P. Dijksma Aude Dujardin Cristina M. Placinta | 1998 | European Journal of Plant Pathology1998，，8： | 1 |
| 17 | Neuroflament light and heterogeneity of disease progression in amyotrophic lateral sclerosis:development and validation of a prediction model to improve interventional trials显示文摘Background:Interventional trials in amyotrophic lateral sclerosis(ALS)sufer from the heterogeneity of the disease as it considerably reduces statistical power.We asked if blood neuroflament light chains(NfL)could be used to antici‑pate disease progression and increase trial power.Methods:In 125 patients with ALS from three independent prospective studies-one observational study and two interventional trials-we developed and externally validated a multivariate linear model for predicting disease pro‑gression,measured by the monthly decrease of the ALS Functional Rating Scale Revised(ALSFRS-R)score.We trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis:NfL levels,sex,age,site of onset,body mass index,disease duration,ALSFRS-R score,and monthly ALSFRS-R score decrease since disease onset.We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials.We analyzed the impact on trial power in mixed-efects models and compared the performance of the NfL model with two currently used predictive approaches,which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period(lead-in)or since disease onset(ΔFRS).Results:Among the parameters provided,the NfL levels(P<0.001)and the interaction with site of onset(P<0.01)contributed signifcantly to the prediction,forming a robust NfL prediction model(R=0.67).Model application in the trial cohorts confrmed its applicability and revealed superiority over lead-in andΔFRS-based approaches.The NfL model improved statistical power by 61%and 22%(95%confdence intervals:54%-66%,7%-29%).Conclusion:The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could signif‑cantly increase the trial power.NCT00868166,registered March23,2009;NCT02306590,registered December 2,2014. | Simon Witzel Felix Frauhammer† Petra Steinacker David Devos Pierre‑François Pradat Vincent Meininger Stefen Halbgebauer Patrick Oeckl Joachim Schuster Simon Anders Johannes Dorst Markus Otto Albert C.Ludolph | 2021 | Translational Neurodegeneration2021，10，3： | 1 |
| 18 | Splenic hemangioma显示文摘 | David GD Felix SC | 1991 | AJR1991，157，7： | 1 |
| 19 | Role of Molecular Agents and Targeted Therapy in Clinical Trials for Women With Ovarian Cancer显示文摘 | Jonathan A. Ledermann Christian Marth Mark S. Carey Michael Birrer David D.L. Bowtell Stan Kaye Iain McNeish Amit Oza Giovanni Scambia Gordon Rustin Frederick B. Stehman David Gershenson Gillian Thomas Els Berns Antonio Casado Nelleke Ottevanger Felix Hil | 2011 | International Journal of Gynecological Cancer2011，，4： | 1 |
| 20 | Mobile vs. fixed bearing unicondylar knee arthroplasty: A randomized study on short term clinical outcomes and knee kinematics显示文摘 | Ming G. Li Felix Yao Brendan Joss James Ioppolo Bo Nivbrant David Wood | 2006 | The Knee2006，，5： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员