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Identification and optimization of a potent and highly selective D3 dopamine receptor agonist

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中国药理学与毒理学杂志 2017年第10期31卷 950-951页

作者： Amy E MOrITZ r benjamin free Warren WEINEr Muzna BACHANI Trevor DOYLE Noel SOUTHALL Marc FErrEr Jonathan A JAVITCH Joseph STEINEr Ara ABrAMYAN Lei SHI Jeffrey AUBé Kevin FrANKOWSKI David r SIBLEY Molecular Neuropharmacology Section National Institute of Neurological Disorders and StrokeNational Institutes of Health Bethesda MD 20814 University of North Carolina Chapel Hill NC27599 Neurotherapeutic Development Unit National Institute of Neurological Disorders and StrokeNational Institutes of Health Bethesda MD 20814 National Center for Advancing Translational Sciences Rockville MD 20892 Columbia University New York NY 10032 Computational Chemistry and Molecular Biophysics Unit Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse National Institutes of Health Baltimore MD 21224

OBJECTIVE Dopamine receptors(Drs) are involved in the development and treatment of many neuropsychiatric *** available dopaminergic drugs modulate both DrD2 and DrD3,leading to side effects and uncertainty as to the roles each Dr subtype plays *** lab employed high throughput screening paradigms to discover highly selective modulators for the *** The NIH Molecular Libraries Program 400,000 + small molecule library was screened using the Discove rx Path Hunter?β-arrestin assay for compounds that activate the DrD3 without effects on the *** and counter-screens assessed selectivity and mechanisms of *** identified 62 potential agonists,and chose the most promising to perform a structure-activity relationship(SAr) study to increase potency while maintaining *** lead compound identified through this process,ML417,was also characterized using bioluminescence resonance energy transfer(BrET)-based β-arrestin recruitment and G-protein activation assays as well as p-ErK *** neuroprotective properties of this compound were assessed using a SHSY5 Y neuronal cell *** ML417 displays potent,DrD3-selective agonist activity in multiple functional *** and functional GPCr screens(>165 receptors) show ML417 has limited cross-reactivity with other ***417 also displays superior(compared to the reference compound pramipexole),dose-dependent protection against a decrease in neurite length induced by 10 μmol·L^(-1) of the neurotoxin,6-hydroxydopamine,in the SHSY5 Y cell *** We have discovered and characterized ML417,a potent and highly selective DrD3 *** compound will be useful as a research tool,and may prove useful as a therapeutic drug lead.

关键词： Dopamine receptor high throughput screening subtype selectivity neuroprotection

Traditional Chinese medicine “Qing Yi Tang” alleviates oxygen free radical injury in acute necrotizing pancreatitis

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World Journal of Gastroenterology 1998年第4期4卷 85-87页

作者： LI ZhanLiang1, WU ChengTang2, LU Lianrong, ZHU XiaoFeng and XIONG DeXinKeywords pancreatitis/therapy Qing Yi Tang free radicals superoxide dismutase/analysis malonyldiadehyde/analysis 304th Hospital of PLA Beijing 100037 China Nanfang Hospital First Military Medical University Guangzhou 510515 China Kharkov Medical School Ukraine Department of Surgery China 304th Hospital of PLA Beijing 100037 51 Fucheng Rd China

AIM To observe the changes in oxygen free radical (OFr) and the curative effect of traditional Chinese medicine 'Qing Yi Tang' in acute necrotizing pancreatitis (ANP).METHODS After induction of ANP by injection of sodium taurocholate into pancreatic duct, 16 dogs were randomly divided into control group and Chinese medicine group. Serum amylase, SOD and MDA were determined on postoperative day 1, 2, 4 and 7. The animals were sacrificed on day 7. SOD and MDA in organs were determined, and pathological changes in pancreas were *** As compared with control group, the serum level of amylase (734U/L vs 2783U/L) and MDA (7.8nmol/ml vs 14.8nmol/ml) in Chinese medicine group were decreased on day 7 (P＜0.05), while SOD increased significantly (281nU/ml vs 55nU/ml, P＜0.01), and similar changes occurred in MDA and SOD in organs, especially in the pancreas; the pathological changes in the pancreas were alleviated as *** 'Qing Yi Tang' is effective in clearing OFrs and alleviating pathological changes in ANP.

关键词： pancreatitis therapy Qing Yi Tang free radicals superoxide dismutase analysis malonyldiadehyde analysis

free vibration and transient response of double curved beams connected by intermediate straight beams

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 37-62页

作者： r.A.JAFArI-TALOOKOLAEI H.GHANDVAr E.JUMAEV S.KHATIr T.CUONG-LE School of Mechanical Engineering Babol Noshirvani University of Technology Department of Mechanical Engineering Faculty of Engineering New Uzbekistan University University of Business and Science Center for Engineering Application and Technology Solutions Ho Chi Minh City Open University

This paper investigates the free vibration and transient response of interconnected structures including double curved beams and intermediate straight beams,which are all constructed from functionally graded porous(FGP) materials. The strain potential and kinetic energies of each beam along with the work done by the external force are calculated. Additionally, a higher-order beam element is introduced to derive stiffness and mass matrices, along with the force vector. The curved and straight beams are discretized, and their assembled stiffness, mass matrices, and force vectors, are *** conditions at the joints are used to derive the total matrices of the entire structure. Subsequently, the natural frequencies and transient response of the system are determined. The accuracy of the mathematical model and the self-developed computer program is validated through the comparison of the obtained results with those of the existing literature and commercial software ANSYS, demonstrating excellent ***, a comprehensive study is conducted to investigate the effects of various parameters on the free vibration and transient response of the considered structure.

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Test Elements, Generic Elements and Almost Primitivity in free Products

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Algebra Colloquium 2016年第2期23卷 263-280页

作者： Ann-Kristin Engel benjamin Fine Gerhard rosenberger Faculty of Mathematics TU-Braunschweig 38106 Braunschweig Germany Department of Mathematics Fairfield University Fairfield Connecticut 06430 USA Fachbereich Mathematik University of Hamburg Bundesstrasse 55 20146 Hamburg Germany FIM University of Passau Innstrasse 33 94032 Passau Germany

In [5, 6] the relationships between test words, generic elements, almost primitivity and tame almost primitivity were examined in free groups. In this paper we extend the concepts and connections to general free produ... 详细信息

关键词： test elements generic elements almost primitive elements free products

A comprehensive investigation on nonlinear vibration and bending characteristics of bio-inspired helicoidal laminated composite structures

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 81-100页

作者： S.SAUrABH r.KIrAN D.SINGH r.VAISH V.S.CHAUHAN School of Mechanical and Materials Engineering Indian Institute of Technology Mandi

Bio-inspired helicoidal composite laminates, inspired by the intricate helical structures found in nature, present a promising frontier for enhancing the mechanical properties of structural designs. Hence, this study provides a comprehensive investigation into the nonlinear free vibration and nonlinear bending behavior of bio-inspired composite plates. The inverse hyperbolic shear deformation theory(IHSDT) of plates is employed to characterize the displacement field, with the incorporation of Green-Lagrange nonlinearity. The problem is modeled using the C0finite element method(FEM), and an in-house code is developed in the MATLAB environment to solve it numerically. Various helicoidal layup configurations including helicoidal recursive(Hr), helicoidal exponential(HE), helicoidal semi-circular(HS), linear helicoidal(LH), and Fibonacci helicoidal(FH)with different layup sequences and quasi-isotropic configurations are studied. The model is validated, and parametric studies are conducted. These studies investigate the effects of layup configurations, side-to-thickness ratio, modulus ratios, boundary conditions, and loading conditions at different load amplitudes on the nonlinear vibration and nonlinear bending behaviors of bio-inspired composite plates. The results show that the laminate sequence exerts a substantial impact on both nonlinear natural frequencies and nonlinear bending behaviors. Moreover, this influence varies across different side-to-thickness ratios and boundary conditions of the bio-inspired composite plate.

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Comparison of population estimators and indices for monitoring house mice in sorghum crops

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Integrative Zoology 2010年第1期5卷 53-62页

作者： Shahram KABOODVANDPOUr Carissa free Luke K.-P.LEUNG Department of Environment Sciences Kurdistan UniversitySanandajKurdistanIran School of Animal Studies University of QueenslandGattonAustralia

House mice(Mus musculus domesticus Schwarz&Schwarz,1943)are monitored in Australia and China to track changes in mouse population densities and forecast their potential damage to cereal *** present study compared population indices based on the number of different mice caught and overall trap success from live-trapping with an oil card index(OC)and a tracking index(T)for monitoring mice in sorghum crops immediately before crop maturation.T was measured as the percentage of track board covered with mouse footprints night-1,and OC as the percentage of card removed by mice *** reliability of these abundance indices was quantified by Pearson correlation coefficient with the trappable population size(Ñ),which was estimated by capture-recapture over eight consecutive nights on 175×5 trapping grids,in sorghum crops on two properties on the Darling Downs,*** of differences among individual mice in capture probability,Model Mh of program MArK was used to account for such heterogeneity and to estimate the size of each mouse *** number of individual animals caught was more strongly correlated withÑthan trap success and,therefore,might be a more reliable index;the data suggest that three trapping occasions provide optimal precision for this index.T correlated significantly withÑonly at sites where the canopy of sorghum plants was closed,and its use should,therefore,be restricted to this *** did not correlate withÑbecause none or very little of the cards was eaten at low to moderate mouse densities.T and the number of animals caught over three trapping nights are recommended for monitoring mice in sorghum crops immediately prior to crop maturation.

关键词： house mouse live-trapping oil card index sorghum track index

Diagnosis and treatment of gastroesophageal reflux disease in infants and children

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World Journal of Gastroenterology 1999年第5期5卷 375-382页

作者： Yvan Vandenplas(PhD.,Academic Children’s Hospital,free University of Brussels,Laarbeeklaan 101) Vrije Universiteit Brussel 比利时

Proposal for pathogenesis-based treatment options to reduce calcium oxalate stone recurrence

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Asian Journal of Urology 2023年第3期10卷 246-257页

作者： Saeed r.Khan benjamin K.Canales Department of Pathology Immunologyand Laboratory MedicineUniversity of FloridaGainesvilleFLUSA Department of Urology University of FloridaGainesvilleFLUSA

Objective:Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30%and 50%despite technological and scientific *** in recurrence would improve patient outcomes and reduce cost and stone *** objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent ***: All relevant literature up to October 2020,listed in PubMed is ***: Clinical guidelines endorse the use of evidence-based medications,such as alkaline agents and thiazides,to reduce urinary mineral supersaturation and ***,there may be additional steps during stone pathogenesis where medications could moderate stone *** calcium oxalate stones grow attached to randall’s plaques or *** of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and *** renin-angiotensin-aldosterone system(rAAS),nicotinamide adenine dinucleotide phosphate(NADPH)oxidase,mitochondria,and NOD-like receptor pyrin domain containing-3(NLrP3)inflammasome have all been implicated at specific steps during stone pathogenesis in animal ***: In addition to supersaturation-reducing therapies,the use of anti-oxidants,free radical scavengers,and inhibitors of NADPH oxidase,NLrP3 inflammasome,and rAAS may prove beneficial for stone *** such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in *** clinical evidence for their use in stone prevention in humans is limited,experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.

关键词： Kidney stones Calcium oxalate Inflammation Inflammasome Supersaturation reactive oxygen species Oxidative stress

Morphology-based classifcation of the fying capacities of aquatic insects: A frst attempt

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Current Zoology 2024年第5期70卷 607-617页

作者： rémi Gerber Christophe Piscart Jean-Marc roussel benjamin Bergerot University of rennes CNRSECOBIO UMR 6553F-35042 RennesFrance DECOD(Ecosystem Dynamics and Sustainability) INRAEInstitut AgroIFREMERRennesFrance

Flight is a key feature of the reproduction and dispersal of emerging aquatic ***,morphological measurements of insect fight are mostly available for terrestrial taxa and dragonfies,while aquatic insects have been poorly *** analyzed 7 fight-related morphological parameters of 32 taxa belonging to 5 orders of emerging aquatic insects(Ephemeroptera,Trichoptera,Plecoptera,Diptera,and Megaloptera)with different life history traits related to fight(dispersal strategy,voltinism,adult lifespan,and swarming behavior).After correcting for allometry,we used an a priori-free approach to cluster the individuals according to their fight-related ***,we explored the levels of agreement between these clusters,taxonomy,and several life history traits of the *** orders were scattered among several clusters,suggesting a large range of fight capacities,particularly for *** found swarming taxa in each cluster,showing that morphological adaptations to swarming are not identical in all aquatic *** clusters did not match the expected dispersal capacity of the taxa as derived from the literature or *** wide-winged insects notably gathered taxa traditionally described as good or weak *** capacities based on morphology partly matched with the taxonomy and life-history traits of aquatic insect *** parameters such as fight propensity,energy stores,and wing kinematics should help refne their fying and dispersal capacity.

关键词： allometry dispersal fight freshwater wing