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Science China(Technological Sciences) 2009年第11期52卷 3335-3347页

作者： KRONVANG Brian WINDOLF JФrgen GRANT Ruth ANDERSEN hans E ThODSEN hans OVESEN niels B LARSEN SФren E National Environmental Research Institute Aarhus University VejlsФvej 25 DK-8600 Silkeborg Denmark

Nationwide monitoring of the aquatic environment was initiated in 1988 in Denmark as a means to follow the outcome of the Action Plans for nutrient pollution of the aquatic environment. Five Action Plans have been adopted by the Danish Parliament since 1985 and the nationwide monitoring programme can be used to quantify the outcome as shown by reductions in nutrient discharges from both point and non-point sources. Moreover, the empirical experience gathered from nearly 20 years of monitoring is assisting the development and calibration of models for simulation of nitrogen leaching, nitrogen removal in groundwater and surface waters and the establishment of a P-index all covering the entire land area of Denmark.

关键词： nitrogen phosphorus monitoring data point sources non-point sources models Action Plans Danish experience

Carboxylesterase 1 family knockout alters drug disposition and lipid metabolism

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Acta Pharmaceutica Sinica B 2023年第2期13卷 618-631页

作者： Changpei Gan Jing Wang Alejandra Martínez-Chávez Michel hillebrand niels de Vries Joke Beukers Els Wagenaar Yaogeng Wang Maria C.Lebre hilde Rosing Sjoerd Klarenbeek Rahmen Bin Ali Colin Pritchard Ivo huijbers Jos h.Beijnen Alfred h.Schinkel Division of Pharmacology the Netherlands Cancer InstituteAmsterdam 1066 CXthe Netherlands Department of Pharmacy&Pharmacology the Netherlands Cancer InstituteAmsterdam 1066 CXthe Netherlands Division of Pharmacoepidemiology and Clinical Pharmacology Utrecht Institute for Pharmaceutical SciencesUtrecht UniversityUtrecht 3584 CSthe Netherlands Experimental Animal Pathology Facility the Netherlands Cancer InstituteAmsterdam 1066 CXthe Netherlands Mouse Clinic for Cancer and Aging(MCCA)Transgenic Facility the Netherlands Cancer InstituteAmsterdam 1066 CXthe Netherlands

The mammalian carboxylesterase 1(Ces1/CES1)family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous *** investigate the pharmacological and physiological roles of Ces1/CES1,we generated Ces1 cluster knockout(Ces1^(-/-))mice,and a hepatic human CES1 transgenic model in the Ces1^(-/-)background(TgCES1).Ces1^(-/-)mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and ***1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and ***1 and hCES1 activity increased irinotecan toxicity,likely by enhancing the formation of pharmacodynamically active ***1^(-/-)mice also showed markedly increased capecitabine plasma exposure,which was moderately decreased in TgCES1 ***1^(-/-)mice were overweight with increased adipose tissue,white adipose tissue inflammation(in males),a higher lipid load in brown adipose tissue,and impaired blood glucose tolerance(in males).These phenotypes were mostly reversed in TgCES1 ***1 mice displayed increased triglyceride secretion from liver to plasma,together with higher triglyceride levels in the male *** results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and ***1^(-/-)and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.

关键词： Ces1/CES1 enzymes Irinotecan Capecitabine Adipose tissue Lipid homeostasis Inflammation Triglyceride mobilization Mouse models

Sirtuins in B lymphocytes metabolism and function

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World Journal of Experimental Medicine 2019年第1期9卷 1-13页

作者： Bruno Ghirotto Fernanda Fernandes Terra niels Olsen Saraiva Camara Paulo José Basso Department of Immunology Institute of Biomedical Sciences University of Sao Paulo Division of Nephrology School of Medicine Federal University of Sao Paulo Laboratory of Renal Physiology (LIM 16) School of MedicineUniversity of S?o Paulo

Sirtuins(SIRTs) are NAD+-dependent histone deacetylases and play a role in virtually all cell biological processes. As SIRTs functions vary according to their subtypes, they can either activate or inhibit signaling pathways upon different conditions or tissues. Recent studies have focused on metabolic effects performed by SIRTs in several cell types since specific metabolic pathways(e.g., aerobic glycolysis, oxidative phosphorylation, β-oxidation, glutaminolysis) are used to determine the cell fate. however, few efforts have been made to understand the role of SIRTs on B lymphocytes metabolism and function. These cells are associated with humoral immune responses by secreting larger amounts of antibodies after differentiating into antibody-secreting cells. Besides, both the SIRTs and B lymphocytes are potential targets to treat several immune-mediated disorders, including cancer. here, we provide an outlook of recent studies regarding the role of SIRTs in general cellular metabolism and B lymphocytes functions, pointing out the future perspectives of this field.

关键词： B cells Metabolic sensors histone deacetylases Cancer

INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2018年第2期24卷 195-210页

作者： Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt henrik h hansen Li C Chen Mathieu Petitjean Weslyn Friley niels Vrang Jacob Jelsing Mark Young Intercept Pharmaceuticals Intercept PharmaceuticalsSan DiegoCA 92121United States Gubra Hoersholm DK-2970Denmark PharmaNest Genesis Imaging ServicesPrincetonNJ 08540United States Qualyst Transporter Solutions DurhamNC 27713United States

AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASh).METhODS The effects of INT-767 on histological features of NASh were assessed in two studies using Lep^(ob/ob)(ob/ob) NASh mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASh mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASh study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASh. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass *** INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASh histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potenti

关键词： Non-alcoholic steatohepatitis INT-767 Obeticholic acid Liver biopsy FXR TGR5 Mouse model

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学习分析:当前的挑战与未来的发展

开放教育研究 2020年第2期26卷 40-40,42-46页

作者： niels Pinkwart 洪堡大学计算机科学系德国柏林10099

一、引言学习分析研究过去几年取得了巨大进步,并将于2020年在德国法兰克福召开第10届学习分析与知识国际会议(LAK)。可以肯定的是,这一研究领域将继续发展——以数据驱动的方法辅助学习,以数据驱动更好地理解学习与教学方法,在不久的... 详细信息

一、引言学习分析研究过去几年取得了巨大进步,并将于2020年在德国法兰克福召开第10届学习分析与知识国际会议(LAK)。可以肯定的是,这一研究领域将继续发展——以数据驱动的方法辅助学习,以数据驱动更好地理解学习与教学方法,在不久的将来是不太可能消失的。但不是所有与学习分析相关的研究愿景都已经实现,有几个领域的研究还需要发展,以克服学习分析领域当前面临的挑战,并在教育实践中有所作为。已有综述文章采用网络分析方法(Dawson et al.,2014),或者是通过论证(De Rosa,2017)系统地(Fischer et al.,in press;Avella et al.,2016)对学习分析(或相关的教育数据挖掘)的未来发展进行了展望。本文将重点放在学习者方面,突出当前学习分析研究面临挑战和机遇的三个示范性领域,每个领域各用两个案例说明。总的来说,这也许可以(至少部分地)描绘出学习分析的未来发展路径。

关键词：德国法兰克福数据驱动网络分析方法辅助学习教育数据挖掘挑战与未来示范性

Mesenteric traction syndrome in pigs:A single-blinded,randomized controlled trial

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Animal Models and Experimental Medicine 2021年第2期4卷 162-168页

作者： Rune B.Strandby Jens T.F.Osterkamp Rikard Ambrus Amelie henriksen Jens P.Goetze niels h.Secher Michael P.Achiam Lars-Bo Svendsen Department of Surgical Gastroenterology RigshospitaletUniversity of CopenhagenCopenhagenØDenmark Department of Clinical Biochemistry RigshospitaletUniversity of CopenhagenCopenhagenØDenmark Department of Anaesthesia RigshospitaletUniversity of CopenhagenCopenhagenØDenmark

Background:Mesenteric traction syndrome is commonly observed in patients undergoing upper abdominal surgery and is associated with severe postoperative complications.A triad of hypotension,tachycardia,and facial flushing seems provoked by prostacyclin(PGI 2)release from the gut in response to mesenteric *** administration of nonsteroidal anti-inflammatory drugs(NSAID)inhibits PGI 2 release,stabilizing the hemodynamic ***,we examined the effect of mesenteric traction on splanchnic blood flow in pigs randomized to NSAID or placebo *** and Methods:Twenty pigs were allocated to either ketorolac or pla-cebo *** minutes of manual mesenteric traction was *** 6-keto-PGF1,a stable metabolite of PGI 2,hemodynamic variables,and regional blood flow(laser speckle contrast imaging)to the liver,stomach,small intestine,upper lip,and snout(laser Doppler flowmetry)were recorded prior to traction and 5 and 30 minutes ***:Both groups of pigs presented a decrease in systemic vascular resistance(P.01),mean arterial blood pressure(P.001),and blood flow in the gastric an-trum(P.002).Plasma 6-keto-PGF1 did not increase in either group(P.195),and cardiac output,heart rate,central venous pressure,and blood flow to the liver,small intestine,upper lip,and snout remained ***:Mesenteric traction resulted in cardiovascular depression,including re-duced blood flow in the gastric *** 6-keto-PGF1 did not increase,and ketorolac administration did not alter the response to mesenteric *** studies are needed to identify which substance is responsible for eliciting the cardio-vascular response to mesenteric traction in pigs.

关键词： 6-keto-PGF1 gastric blood flow hemodynamics laser speckle contrast imaging mesenteric traction syndrome prostacyclin

SNOWY COTYLEDON 2 Promotes Chloroplast Development and has a Role in Leaf Variegation in Both Lotus japonicus and Arabidopsis thaliana

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Molecular Plant 2017年第5期10卷 721-734页

作者： Nicola Zagari Omar Sandoval-lbanez niels Sandal Junyi Su Manuel Rodriguez-Concepcion Jens Stougaard Mathias Pribil Dario Leister Pablo Pulido Plant Molecular Biology Department of Biology I Ludwig-Maximilians-Universitat Munchen 82152 Planegg-Martinsried Germany Copenhagen Plant Science Center University of Copenhagen 1871 Frederiksberg C Denmark Research and Innovation Center Fondazione Edmund Mach via E. Mach 1 38010 San Michele all'Adige Italy Centre for Carbohydrate Recognition and Signalling Department of Molecular Biology and Genetics Aarhus University Gustav Wieds Vej 10 8000 Aarhus C Denmark Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB Campus UAB Bellaterra 08193 Barcelona Spain

Plants contain various factors that transiently interact with subunits or intermediates of the thylakoid multiprotein complexes, promoting their stable association and integration. hence, assembly factors are essential for chloroplast development and the transition from heterotrophic to phototrophic growth. Snowy cotyledon 2 （SCO2） is a DNAJ-like protein involved in thylakoid membrane biogenesis and interacts with the light-harvesting chlorophyll-binding protein LhCBI. In Arabidopsis thaliana, SCO2 function was previ- ously reported to be restricted to cotyledons. here we show that disruption of SC02 in Lotus japonicus results not only in paler cotyledons but also in variegated true leaves. Furthermore, smaller and pale- green true leaves can also be observed in A. thaliana sco2 （atsco2） mutants under short-day conditions. In both species, SCO2 is required for proper accumulation of PSlI-LhCll complexes. In contrast to other variegated mutants, inhibition of chloroplastic translation strongly affects L. japonicus sco2 mutant devel- opment and fails to suppress their variegated phenotype. Moreover, inactivation of the suppressor of variegation AtClpR1 in the atsco2 background results in an additive double-mutant phenotype with variegated true leaves. Taken together, our results indicate that SCO2 plays a distinct role in PSll assembly or repair and constitutes a novel factor involved in leaf variegation.

关键词： SCO2 DNAJ-like photosynthesis assembly factor variegation chloroplast development

Fatty acid intake in relation to reproductive hormones and testicular volume among young healthy men

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Asian Journal of Andrology 2017年第2期19卷 184-190页

作者： Lidia Minguez-Alarcon Jorge E Chavarro JJaime Mendiola Manuela Roca Cigdem Tanrikut Jesus Vioque niels Jorgensen Alberto M Torres-Cantero Department of Environmental health Harvard School of Public Health Boston Massachusetts USA Department of health and Social Sciences Division of Preventive Medicine and Public Health University of Murcia School of Medicine IMIB-Arrixaca Espinardo (Murcia) Spain Department of Nutrition Harvard School of Public Health Boston Massachusetts USA Department of Epidemiology Harvard School of Public Health Boston Massachusetts USA Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA Roca Fertility Advanced Clinic Management SLU Murcia Spain Department of Urology Massachusetts General Hospital Boston Massachusetts USA Department of Surgery Harvard Medical School Boston Massachusetts USA ClBER Epidemiology and Public health (ClBERESP) Institute of Health Ill (ISClII) Madrid Spain Department of Public health Miguel Hernandez University EIche-Alicante Spain Department of Growth and Reproduction University of Copenhagen Rigshospitalet Copenhagen Denmark Regional Campus of International Excellence 'Campus Mare Nostrum' University of Murcia Murcia Spain

Emerging evidence suggests that dietary fats may influence testicular function. however, most of the published literature on this field has used semen quality parameters as the only proxy for testicular function. We examined the association of fat intake with circulating reproductive hormone levels and testicular volume among healthy young Spanish men. This is a cross-sectional study among 209 healthy male volunteers conducted between October 2010 and November 2011 in Murcia Region of Spain. Participants completed questionnaires on lifestyle, diet, and smoking, and each underwent a physical examination, and provided a blood sample. Linear regression was used to examine the association between each fatty acid type and reproductive hormone levels and testicular volumes. Monounsaturated fatty acids intake was inversely associated with serum blood levels of calculated free testosterone, total testosterone, and inhibin B. A positive association was observed between the intake of polyunsaturated fatty acids, particularly of omega-6 polyunsaturated fatty acids, and luteinizing hormone concentrations. In addition, the intake of trans fatty acids was associated with lower total testosterone and calculated free testosterone concentrations （Ptrend = 0.01 and 0.02, respectively）. The intake of omega-3 polyunsaturated fatty acids was positively related to testicular volume while the intake of omega-6 polyunsaturated fatty acids and trans fatty acids was inversely related to testicular volume. These data suggest that fat intake, and particularly intake of omega 3, omega 6, and trans fatty acids, may influence testicular function.

关键词： fat intake reproductive health reproductive hormones trans fatty acids young healthy men

Measurement of the electronic structure of a type-Ⅱ topological Dirac semimetal candidate VAI_(3) using angle-resolved photoelectron spectroscopy

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钨科技(英文) 2023年第3期5卷 332-338页

作者： hong-Wei Fang Ai-Ji Liang niels B.M.Schroter Sheng-Tao Cui Zhong-Kai Liu Yu-Lin Chen School of Physical Science and Technology ShanghaiTech UniversityShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China ShanghaiTech Laboratory for Topological Physics ShanghaiTech UniversityShanghai 201210China Max Planck Institute of Microstructure Physics Halle 06120Germany National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China Department of Physics University of OxfordOxford OX13PUUnited Kingdom

Type-Ⅱ topological Dirac semimetals are topological quantum materials hosting Lorentz-symmetry breaking type-Ⅱ Dirac fermions,which are tilted Dirac cones with various exotic physical properties,such as anisotropic chiral anomalies and novel quantum *** now,only limited material systems have been confirmed by theory and experiments with the type-Ⅱ Dirac ***,we investigated the electronic structure of a new type-Ⅱ Dirac semimetal VA1_(3) with angle-resolved photoelectron *** measured band dispersions are consistent with the theoretical prediction,which suggests the Dirac points are located close to(at about 100 meV above) the Fermi *** work demonstrates a new type-Ⅱ Dirac semimetal candidate system with different Dirac node configurations and application potentials.

关键词： Dirac semimetal.Electronic structure Angle-resolved photoelectron spectroscopy K evaporation

Evapotranspiration of Cotton, <i>Apocynum pictum</i>, and <i>Zyzyphus jujuba</i>in the Tarim Basin, Xinjiang, China

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Journal of Water Resource and Protection 2015年第13期7卷 1101-1109页

作者： niels Thevs Ahemaitijiang Rouzi World Agroforestry Centre Bishkek Kyrgyzstan University of Greifswald Greifswald Germany

Evapotranspiration is a crucial component of the water balance of ecosystems and landscapes, especially under arid climates. In the Tarim Basin, China, there is an increasing competition for water between irrigated agriculture, mainly cotton, and natural ecosystems, which results in periods of water shortage. Such water shortages also impact on cotton. Therefore, alternative crops have been searched for, which eventually withstand such periodical water shortages better than irrigated cotton, notably Zyzyphus jujuba and Apocynum pictum. The fruit tree Z. jujuba has been promoted from the previous decade onward in parts of the Tarim Basin. A. pictum is used as medicinal plant and in a small scale as fiber crop. A. pictum is a perennial herb, which is part of the natural riparian vegetation along the rivers of the Tarim Basin and which grows without irrigation. Therefore, the objective of this paper is to investigate the crop evapotranspiration (ETc) of those three plant species over the growing season. In this paper, the Penman-Monteith approach was employed. Daily means of stomatal resistance in June was 118 s/m, 222 s/m, and 927 s/m for cotton, A. pictum leafs, and Z. jujuba, respectively. In October, those daily mean stomatal resistance climbed to 885 s/m and 742 s/m for cotton and A. pictum leafs, respectively. ETc over the growing season was 514.7 mm for cotton, 217.2 mm for A. pictum, and 339 mm for Z. jujuba. The Kc value of Z. jujuba was in the range of other fruit trees. In this study cotton attained high yields compared to world average yields at a low ETc. This high water use efficiency was achieved through a shift from flood to drip irrigation, the utilization of plastic mulch, and breeding of cotton varieties.

关键词： Evapotranspiration Stomatal Conductance Stomatal Resistance Penman-Monteith Remote Sensing