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Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in brazilian patients

World Journal of Gastroenterology 2014年第12期20卷 3327-3334页

作者： Ana Teresa P Carvalho barbara C esberard renata s b fróes Davy C M Rapozo Ana b Grinman Tatiana A simo Juliana C V C santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor s P de souza Disciplina de Gastroenterologia e Endoscopia Digestiva Universidade do Estado do Rio de Janeiro Programa de Carcinogênese Molecular Instituto Nacional de Cancer Laboratório de Toxicologia e biologia Molecular Universidade do Estado do Rio de Janeiro servi?o de Gastroenterologia Departamento de Clínica MédicaUniversidade Federal do Rio de Janeiro

AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IbD)patients from southeastern brazil.METHODs:A total of 219 consecutive patients with IbD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the state University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IbD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/sodium Dodecyl sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.ResULTs:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUsION:The prevalence of TPMT genotypes was high among brazilian patients.Variants genes*2and*3C may be ass

关键词： Inflammatory bowel disease Thiopurinemethyl-transf

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Quantized autoencoder(QAE)intrusion detection system for anomaly detection in resource-constrained loT devices using RT-loT2022 dataset

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Cybersecurity 2024年第2期7卷 13-27页

作者： b s sharmila Rohini Nagapadma Depatment of Electronics and Communication Engineering The National Institute of EngineeringMysoreKarnataka 570008India

In recent years,many researchers focused on unsupervised learning for network anomaly detection in edge devices to identify attacks.The deployment of the unsupervised autoencoder model is computationally expensive in resource-constrained edge devices.This study proposes quantized autoencoder(QAE)model for intrusion detection systems to detect anomalies.QAE is an optimization model derived from autoencoders that incorporate pruning,clustering,and integer quantization techniques.Quantized autoencoder uint8(QAE-u8)and quantized autoencoder float16(QAE-f16)are two variants of QAE built to deploy computationally expensive Al models into Edge devices.First,we have generated a Real-Time Internet of Things 2022 dataset for normal and attack traffic.The autoencoder model operates on normal traffic during the training phase.The same model is then used to reconstruct anomaly traffic under the assumption that the reconstruction error(RE)of the anomaly will be high,which helps to identify the attacks.Furthermore,we study the performance of the autoencoders,QAE-u8,and QAE-f16 using accuracy,precision,recall,and F1 score through an extensive experimental study.We showed that QAE-u8 outperforms all other models with a reduction of 70.01%in average memory utilization,92.23%in memory size compression,and 27.94%in peak CPU utilization.Thus,the proposed QAE-u8 model is more suitable for deployment on resource-constrained IoT edge devices.

关键词： IoT constrained system

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study of hybrid nanofluid flow in a stationary cone-disk system with temperature-dependent fluid properties

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 677-694页

作者： A.s.JOHN b.MAHANTHesH G.LORENZINI Center for Mathematical Needs Department of MathematicsCHRIST(Deemed to be University)Karnataka 560029India school of Mathematical and statistical sciences The University of Texas Rio Grande ValleyTexas 78539U.S.A. Department of Engineering and Architecture University of ParmaParma 43124Italy

Cone-disk systems find frequent use such as conical diffusers,medical devices,various rheometric,and viscosimetry applications.In this study,we investigate the three-dimensional flow of a water-based Ag-Mg O hybrid nanofluid in a static cone-disk system while considering temperature-dependent fluid properties.How the variable fluid properties affect the dynamics and heat transfer features is studied by Reynolds's linearized model for variable viscosity and Chiam's model for variable thermal conductivity.The single-phase nanofluid model is utilized to describe convective heat transfer in hybrid nanofluids,incorporating the experimental data.This model is developed as a coupled system of convective-diffusion equations,encompassing the conservation of momentum and the conservation of thermal energy,in conjunction with an incompressibility condition.A self-similar model is developed by the Lie-group scaling transformations,and the subsequent self-similar equations are then solved numerically.The influence of variable fluid parameters on both swirling and non-swirling flow cases is analyzed.Additionally,the Nusselt number for the disk surface is calculated.It is found that an increase in the temperature-dependent viscosity parameter enhances heat transfer characteristics in the static cone-disk system,while the thermal conductivity parameter has the opposite effect.

关键词： hybrid nanofluid cone-disk system laminar flow variable fluid property Nusselt number

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Fuzzy Reliability and Availability of system under a Calendar-based Inspection Involving Multiple Failures and Its Application to Wind Turbine system

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Journal of systems science and systems Engineering 2024年第2期33卷 187-206页

作者： Mintu Kumar Himani Pant s.b.singh Department of Mathematics statistics and Computer science G.B.Pant University of AgricultureTechnologyPantnagarUttarakhandIndia

Uncertainty is an important factor that needs to be considered while analyzing the performance of any engineering system.In order to quantify uncertainty,fuzzy set theory is frequently used by most of researchers,including energy system experts.According to the classical reliability theory,component lifetimes have crisp parameters,but due to uncertainty and inaccuracy in data,it is sometimes very difficult to determine the exact values of these parameters in real-world systems.To overcome this difficulty in the current research,failure and repair rates were taken as triangular fuzzy numbers to determine the fuzzy availability of a system undergoing calendar-based periodic inspection subject to multiple failure modes(FMs).It was assumed that each component in the system had an exponential failure rate and repair rate with fuzzy parameters.system FMs were explicitly taken into account when a functional state of the system was considered.Each FM had a random failure time.On the occurrence of any failure,a random time was selected for the relevant corrective repair work.The proposed research was studied for one of the major sources of green energy,namely a wind turbine system wherein all the derived propositions have been implemented on it.

关键词： Fuzzy reliability fuzzy availability wind turbine system multiple failure modes triangular fuzzy number

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Astrophysical s-factor and reaction rate for 15N(p,γ)16O within the modified potential cluster model

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Chinese Physics C 2024年第4期48卷 130-145页

作者： s.b.Dubovichenko A.s.Tkachenko R.Ya.Kezerashvili N.A.burkova b.M.Yeleusheva Fesenkov Astrophysical Institute 050020 AlmatyKazakhstan New York City College of Technology City University of New YorkBrooklyn11201 New YorkUSA Graduate school and University Center City University of New York10016 New YorkUSA al-Farabi Kazakh National University 050040 AlmatyKazakhstan

We study radiative p^(15)N capture on the ground state of ^(16)O at stellar energies within the framework of a modified potential cluster model(MPCM)with forbidden states,including low-lying resonances.The investigation of the ^(15)N(p,γ0)^(16)O reaction includes the consideration of ^(3)s_(1) resonances due to E1 transitions and the contribution of the ^(3)P_(1) scattering wave in the p+^(15)N channel due to the ^(3)P_(1)→^(3)P_(0)M1 transition.We calculated the astrophysical low-energy s-factor,and the extrapolated s(0)turned out to be within 34.7−40.4 keV·b.The important role of the asymptotic constant(AC)for the ^(15)N(p,γ0)16O process with interfering ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances is elucidated.A comparison of our calculation for the s-factor with existing experimental and theoretical data is addressed,and a reasonable agreement is found.The reaction rate is calculated and compared with the existing rates.It has negligible dependence on the variation of AC but shows a strong impact of the interference of ^(3)s_(1)(312)and ^(3)s_(1)(962)resonances in reference to the CNO Gamow windows,especially at low temperatures.We estimate the contribution of cascade transitions to the reaction rate based on the exclusive experimental data from Phys.Rev.C.85,065810(2012).The reaction rate enhancement due to the cascade transitions is observed from T_(9)>0.3 and reaches the maximum factor~1.3 at T_(9)=1.3.We present the Gamow energy window and a comparison of rates for radiative proton capture reactions ^(12)N(p,γ)^(13)O,^(13)N(p,γ)^(14)O,^(14)N(p,γ)^(15)O,and ^(15)N(p,γ)^(16)O obtained in the framework of the MPCM and provide the temperature windows,prevalence,and significance of each process.

关键词： low and astrophysical energies p^(15)N system thermonuclear reaction rate potential cluster model CNO-cycle

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Direct microwave leaching conditions of rare earth elements in fluorescent wastes

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Journal of Rare Earths 2024年第6期42卷 1165-1174,I0007页

作者： A.bilen b.birol M.N.saridede s.s.Kaplan M.s.sonmez Department of Metallurgical and Materials Engineering Yildiz Technical UniversityIstanbulTurkey Department of Chemical Engineering and Materials science Stevens Institute of TechnologyNew JereyUSA Department of Metallurgical and Materials Engineering Istanbul Technical UniversityIstanbulTurkey

The luminescent phosphor powder in the fluorescent lamp constitutes 2%of the lamp’s weight.It can be mentioned that fluorescent wastes are a crucial raw material to produce rare earth oxides.In the present study,microwave leaching process was conducted to dissolve rare earth elements yttrium(Y),europium(Eu),and remaining rare earth elements(REes)present in the phosphor powder of the fluorescent lamp.and the yields were compared.In the microwave leaching process,the effects of the temperature(80-160℃),acid type(hydrochloric acid(HCl),nitric acid(HNO_(3)),sulphuric acid(H_(2)sO_(4))),acid concentration(0.5-6 mol/L),solid to liquid ratio(0.1:10-0.5:10)and reaction time(5-90 min)parameters on leaching efficiencies of varying rare earth elements and calcium were investigated.The highest yield was obtained in the direct microwave leaching of fluorescent waste with the experimental conditions of 6 mol/L HCl,160℃,0.1:10 solid-to-liquid ratio(s:L),and 90 min.Activation energy calculations were made,and kinetic models of the reactions were obtained,and it is observed that Y and Eu dissolution is diffusion-controlled,on the other hand,lanthanum(La),cerium(Ce),and terbium(Tb)were examined to be chemical reaction controlled.Moreover,calcium(Ca)and gadolinium(Gd)seem coherent with the mixed model.Concurrently,mathematical models of all experimental studies are created with the response surface box-behnken method and the correlation coefficients of all the models are over 90%.

关键词： Rare earth elements(REes) Direct microwave leaching Fluorescent waste Kinetic models Response surface method

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Weighted Probability Density estimator with Updated bandwidths

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Journal of systems science & Complexity 2024年第2期37卷 886-906页

作者： WU Yi YU Wei WANG Xuejun PRAKAsA RAO b L s school of big Data and Artificial Intelligence Chizhou UniversityChizhou 247000China school of big Data and statistics Anhui UniversityHefei 230601China CR Rao Advanced Institute of Mathematics Statistics and Computer ScienceHyderabad 500046India

In this paper,the authors study a class of weighted version of probability density estimator.It is shown that the weighted estimator contains some existing estimators of probability density,no matter they are recursive or non-recursive.some statistical results including weak consistency,strong consistency,rate of strong consistency,and asymptotic normality are established under some mild conditions.Moreover,the random weighted estimator is also investigated.some numerical simulations and a real data analysis are presented to study the numerical performances of the estimators.

关键词： Asymptotic normality consistency numerical simulation probability density real data analysis updated bandwidths weighted estimator

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Thermo-kinetic characteristics on stabilizing hetero-phase interface of metal matrix composites by crystal plasticity finite element method

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Journal of Materials science & Technology 2024年第2期169卷 53-67页

作者： Y.b.Zhang s.J.song F.Liu state Key Laboratory of solidification Processing Northwestern Polytechnical UniversityXi’an 710072China Analytical&Testing Center Northwestern Polytechnical UniversityXi’an 710072China

Using dislocation-based constitutive modeling in three-dimension crystal plasticity finite element(3D CPFE)simulations,co-deformation and instability of hetero-phase interface in different material systems were herein studied for polycrystalline metal matrix composites(MMCs).Local stress and strain fields in two types of 3layer MMCs such as fcc/fcc Cu-Ag and fcc/bcc Cu-Nb have been predicted under simple compressive deformations.Accordingly,more severe strain-induced interface instability can be observed in the fcc/bcc systems than in the fcc/fcc systems upon refining to metallic nanolayered composites(MNCs).by detailed analysis of stress and strain localization,it has been demonstrated that the interface instability is always accompanied by high-stress concentration,i.e.,thermodynamic characteristics,or high strain prevention i.e.,kinetic characteristics,at the hetero-phase interface.It then follows that the thermodynamic driving forceG and the kinetic energy barrier Q during dislocation and shear banding can be adopted to classify the deformation modes,following the so-called thermo-kinetic correlation.Then by inserting a high density of high-energy interfaces into the Cu-Nb composites,such thermo-kinetic integration at the hetero-phase interface allows a successful establishment of MMCs with the high△G-high Q deformation mode,which ensures high hardening and uniform strain distri-bution,thus efficiently suppressing the shear band,stabilizing the hetero-phase interface,and obtaining an exceptional combination in strength and ductility.such hetero-phase interface chosen by a couple of thermodynamics and kinetics can be defined as breaking the thermo-kinetic correlation and has been proposed for artificially designing MNCs.

关键词： Thermodynamics and kinetics Physics-based constitutive modeling Hetero-phase interface Crystal plasticity finite element

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Complexed amino acid minerals vs. bis-glycinate chelated minerals:Impact on the performance of old laying hens

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Animal Nutrition 2024年第1期16卷 395-408页

作者： Marcos J.b.santos Maria C.M.M.Ludke Leandro M.silva Carlos b.V.Rabello Mércia R.barros Fabiano s.Costa Clariana s.santos Jamille s.s.Wanderley Department of Animal science Rural Federal University of Pernambuco Department of Veterinary science Rural Federal University of Pernambuco

The present study was to evaluate the effect of trace minerals(Zn, Mn, and Cu) from complexed amino acid minerals(ZMCAA) and bis-glycinate chelated minerals(ZMCGly) in laying hen diets on performance,internal and external egg quality, yolk mineral deposition, intestinal morphometry, and bone characteristics. from 78 to 98 weeks of age, 400 White LsL-Lite strain laying hens were distributed in a randomized design with 4 treatments with 10 replicates per treatment. Treatments were distributed in a 2 ×2 factorial arrangement using either Zn, Mn, and Cu of ZMCAA or ZMCGly source at 2 levels: low(20, 20,and 3.5 mg/kg of Zn, Mn, and Cu, respectively) or high(40, 40, and 7 mg/kg of Zn, Mn, and Cu,respectively). The analysis of variance was performed, and in cases where differences were observed, the means were compared using Tukey?s test(P source and level of trace mineral supplementation had a significant impact on the performance of laying hens. Hens fed ZMCAA had higher egg production(P = 0.01), egg weight(P = 0.02), egg mass(P = 0.01), and lower feed conversion ratio(P =0.05) compared to those fed ZMCGly. The ZMCAA supplementation showed higher albumen height(P =0.01), albumen weight(P = 0.01), and eggshell thickness(P sition of Zn(P s greater for hens received ZMCAA. Tibia weight(P = 0.04)and bone densitometry(P bia were higher with ZMCAA supplementation. In the small intestine, ZMCAA resulted in longer villi(P = 0.02) and shorter crypt depth(P = 0.01) in the duodenum.Jejunum and ileum measurements were influenced by the level and source of trace minerals(P s fed ZMCAA exhibited superior performance, egg quality, deposition of trace minerals in the egg yolk, and bone density compared to hens fed ZMCGly. In this study, older laying hens supplemented with ZMCAA at lower levels demonstrated adequate levels of supplementation.

关键词： bis-glycinates Metal-amino acids Radiodensity Trace minerals

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blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés berardo Cristian R.bacaglio bárbara b.báez Rubén sambuelli Kazim A.sheikh Pablo H.H.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba Departamento de Química biológica-Centro de Investigaciones en Química biológica de Córdoba(CIQUIbIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba Department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated wi

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-barrésyndrome nerve repair ROCK Y-27632

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