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Thiopurine use associated with reduced B and natural killer cells in inflammatory bowel disease

World Journal of Gastroenterology 2017年第18期23卷 3240-3251页

作者： james d lord donna M Shows Translational Research Program Benaroya Research Institute Gastroenterology division Virginia Mason Medical Center

AIM To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo.METHOdS The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease(IBd) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBd at lower doses suggests that they may selectively deplete particular lymphocyte populations. Blood cells from 19 IBd patients on a thiopurine, 19 IBd patients not on a thiopurine, and 38 matched healthy control subjects were analyzed by multiple multi-color flow cytometry panels to quantify the immune cell subsets contained therein, both as a percent of cells, and as an absolute cell count. Similar analyses were performed on colon biopsies from 17 IBd patients on a thiopurine, 17 IBd patients not on a thiopurine, and 49 healthy screening colonoscopy recipients.RESULTS Complete blood counts revealed lower lymphocyte, but not monocyte or granulocyte, counts in IBd patients who were taking thiopurines at the timeof sampling. This reduction was restricted to Cd3-negative lymphocytes, wherein both natural killer(NK) and B cells were significantly reduced among thiopurine recipients. Among Cd19+ B cells, the transitional B cells were particularly depleted, being nearly absent in both blood and colon biopsies of thiopurine recipients. No differences were associated with thiopurine use in Cd8+ T cells, mucosa-associated invariant T(MAIT) cells, invariant natural killer T(i NKT) cells, gamma/delta T cells, Th1, Th17, regulatory T cells(Tregs) or na?ve Cd4+ T cells. However, patients with IBd had significantly more circulating FOXP3+, Helios+ Tregs and fewer iN KT and MAIT cells than healthy controls. CONCLUSION Thiopurine use is associated with reduced B and NK cell, but not T cell, subpopulations in the blood of IBd patients.

关键词： Thiopurine Azathioprine Mercaptopurine 淋巴细胞自然漂亮房间过渡 B 房间煽动性的肠疾病

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Analytical evaluation of steady-state solute distribution in through- diffusion and membrane behavior test under non-perfectly flushing boundary conditions

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第1期16卷 258-267页

作者： Guannian Chen Yuchao Li Kristin MSample-lord Shan Tong School of Civil&Environmental Engineering and Geography Science Ningbo UniversityNingbo315211China MOE Key Laboratory of Soft Soils and Geoenvironmental Engineering College of Civil Engineering and ArchitectureZhejiang UniversityHangzhou310058China Ningbo ZCONE High-tech Company Limited Ningbo315000China department of Civil and Environmental Engineering Villanova UniversityVillanovaPAUSA

The through-diffusion and membrane behavior testing procedure using a closed-system apparatus has been widely used for concurrent measurement of diffusion and membrane efficiency coefficients of low-permeability clay-based barrier materials.However,the common assumption of perfectly flushing conditions at the specimen boundaries could induce errors in analyses of the diffusion coefficients and membrane efficiencies.In this study,an innovative pseudo three-dimensional(3d)analytical method was proposed to evaluate solute distribution along the boundary surfaces of the soil-porous disks system,considering the non-perfectly flushing conditions.The results were consistent with numerical models under two scenarios considering different inflow/outflow positions.The proposed model has been demonstrated to be an accurate and reliable method to estimate solute distributions along the bound-aries.The calculated membrane efficiency coefficient and diffusion coefficient based on the proposed analytical method are more accurate,resulting in up to 50%less relative error than the traditional approach that adopts the arithmetic mean value of the influent and effluent concentrations.The retar-dation factor of the clay specimen also can be calculated with a revised cumulative mass approach.Finally,the simulated transient solute transport matched with experimental data from a multi-stage through-diffusion and membrane behavior test,validating the accuracy of the proposed method.

关键词： diffusion testing Membrane behavior Coupled transport Clay barrier Transport modeling

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Insm1:orchestrating cellular mimicry in the thymus medulla

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Cellular & Molecular Immunology 2024年第4期21卷 414-416页

作者： K.d.james J.E.Cowan UCL Institute of Immunity and Transplantation The Pears BuildingRowland Hill StreetLondonNW32PPUK

The thymus is the primary production site for a functional and self-tolerant T-cell repertoire.The establishment of immune tolerance is mediated by the generation and presentation of tissue-restricted self-antigens(TRAs)by medullary thymic epithelial cells(mTECs),which screen T-cell receptors for self-reactivity to eliminate autoreactive T cells.Recent studies have extended our understanding of mTEC heterogeneity by examining the mechanisms by which mTECs mimic the peripheral self[1].

关键词： medullary eliminate restricted

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Competitive interactions and coexistence of sympatric flagship carnivores in Asia

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Integrative Zoology 2024年第2期19卷 183-199页

作者： Zhilin LI Jiayu LU Xiaoyi SHI Li’an dUO james L.d.SMITH Tianming WANG Tianjin Key Laboratory of Conservation and Utilization of Animal diversity College of Life SciencesTianjin Normal UniversityTianjinChina department of Fisheries Wildlife and Conservation BiologyUniversity of MinnesotaSt.PaulMinnesotaUSA Ministry of Education Key Laboratory for Biodiversity Science and Engineering College of Life SciencesBeijing Normal UniversityBeijingChina National Forestry and Grassland Administration Key Laboratory for Conservation Ecology of Northeast Tiger and Leopard BeijingChina

Understanding the competition and coexistence of flagship carnivores is key to creating strategies for their conservation in the face of global carnivore declines.Although studies exploring the dynamics and competition between tigers(Panthera tigris)and leopards(P.pardus)span decades,there is a lack of understanding regarding the factors that influence their coexistence mechanisms on a broad scale,as well as the drivers determining their exploitative and interference competition.We gathered a comprehensive list of research papers among which 36 papers explored the interspecific interactions between tigers and leopards and tested the influence of biotic and abiotic factors on the coexistence mechanisms along three dimensions using multiple response variables regression models;we also tested the influence of ecological drivers determining the exploitative or interference competition between tigers and leopards.Elevation and ungulate density were the most important predictors in regulating the coexistence mechanisms.Tigers and leopards exhibited more positive relations/higher overlaps as elevation increased in the spatial niche.In addition,they showed a higher dietary overlap in the prey-rich regions.We determined that interference competition between tigers and leopards was less frequently observed in habitats with dense tree cover and homogeneous vegetation structures.Meanwhile,studies with multiple metrics would promote the detection of interference competition.Our study provides new insight into the competitive interactions and coexistence mechanisms of tigers and leopards on a broad scale.Policy-makers and managers should pay more attention to the factors of elevation,prey abundance,and habitat structures for the conservation of tigers and leopards.

关键词： carnivores coexistence mechanisms competitive interactions exploitative competition interference competition

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Nickel sulfate solution fluoride separation with hydrous zirconium oxide

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Tungsten 2024年第2期6卷 367-381页

作者： Elbert M.Nigri Ummul K.Sultana André L.A.Santos james W.Vaughan Sonia d.F.Rocha department of Mining Engineering Federal University of Minas GeraisBelo Horizonte 31270-901Brazil School of Chemical Engineering University of QueenslandSt Lucia 4072Australia

Fluoride is an impurity in nickel sulfate production,which is required for electric vehicle batteries.Hydrous zirconium oxide(HZO)was evaluated for removing fl uoride from nickel sulfate solution.Maximum fluoride removal occurred at pH value 4 and optimal pH value is 4–5,considering Zr solubility.Fluoride availability decreases with pH due to hydrogen fluoride and zirconium fluoride aqueous species.Fluoride removal is initially rapid,with 50 wt.%removal in 7 min,followed by slow removal up to 68 wt.%after 72 h and follows second order rate kinetics.Fluoride removal was dominated by an ion exchange mechanism and resulting Zr–F bonds were observed using Fourier-transform infrared spectroscopy.The presence of nickel sulfate decreased loading capacity compared to a salt-free solution.HZO maintained adsorption capacity through five cycles of loading and regeneration.

关键词： Hydrous zirconium oxide Nickel sulfate Fluoride Adsorption Anion exchange

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Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： Joseph Rich Brian Cole Teng Li Brandon Lu Hanyu Fu Brittany N.Smith Jianping Xia Shujie Yang Ruoyu Zhong james L.doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron d.Franklin Tony Jun Huang department of Biomedical Engineering Duke UniversityDurhamNC 27708USA department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas lord department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid actuation.However,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based processing.To simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet printing.We successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEdOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser doppler vibrometry.Finally,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration experiments.Overall,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

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A Cover-Independent deep Image Hiding Method Based on domain Attention Mechanism

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Computers, Materials & Continua 2024年第3期78卷 3001-3019页

作者： Nannan Wu Xianyi Chen james Msughter Adeke Junjie Zhao School of Computer and Software Nanjing University of Information Science and TechnologyNanjing210044China School of Electronics and Information Engineering Nanjing University of Information Science and TechnologyNanjing210044China

Recently,deep image-hiding techniques have attracted considerable attention in covert communication and high-capacity information hiding.However,these approaches have some limitations.For example,a cover image lacks self-adaptability,information leakage,or weak concealment.To address these issues,this study proposes a universal and adaptable image-hiding method.First,a domain attention mechanism is designed by combining the Atrous convolution,which makes better use of the relationship between the secret image domain and the cover image domain.Second,to improve perceived human similarity,perceptual loss is incorporated into the training process.The experimental results are promising,with the proposed method achieving an average pixel discrepancy(APd)of 1.83 and a peak signal-to-noise ratio(PSNR)value of 40.72 dB between the cover and stego images,indicative of its high-quality output.Furthermore,the structural similarity index measure(SSIM)reaches 0.985 while the learned perceptual image patch similarity(LPIPS)remarkably registers at 0.0001.Moreover,self-testing and cross-experiments demonstrate the model’s adaptability and generalization in unknown hidden spaces,making it suitable for diverse computer vision tasks.

关键词： deep image hiding attention mechanism privacy protection data security visual quality

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi james d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neuro

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Boosting Adversarial Training with Learnable distribution

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Computers, Materials & Continua 2024年第3期78卷 3247-3265页

作者： Kai Chen Jinwei Wang james Msughter Adeke Guangjie Liu Yuewei dai School of Electronics and Information Engineering Nanjing University of Information Science and TechnologyNanjing210044China Key Laboratory of Intelligent Support Technology for Complex Environments Ministry of EducationNanjing210044China School of Computer and Software Nanjing University of Information Science and TechnologyNanjing210044China Nanjing Center for Applied Mathematics Nanjing211135China

In recent years,various adversarial defense methods have been proposed to improve the robustness of deep neural networks.Adversarial training is one of the most potent methods to defend against adversarial attacks.However,the difference in the feature space between natural and adversarial examples hinders the accuracy and robustness of the model in adversarial training.This paper proposes a learnable distribution adversarial training method,aiming to construct the same distribution for training data utilizing the Gaussian mixture model.The distribution centroid is built to classify samples and constrain the distribution of the sample features.The natural and adversarial examples are pushed to the same distribution centroid to improve the accuracy and robustness of the model.The proposed method generates adversarial examples to close the distribution gap between the natural and adversarial examples through an attack algorithm explicitly designed for adversarial training.This algorithm gradually increases the accuracy and robustness of the model by scaling perturbation.Finally,the proposed method outputs the predicted labels and the distance between the sample and the distribution centroid.The distribution characteristics of the samples can be utilized to detect adversarial cases that can potentially evade the model defense.The effectiveness of the proposed method is demonstrated through comprehensive experiments.

关键词： Adversarial training feature space learnable distribution distribution centroid

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How to fill the biodiversity data gap:Is it better to invest in fieldwork or curation?

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Plant diversity 2024年第1期46卷 39-48页

作者： Carlos A.Vargas Marius Bottin Tiina Sarkinen james E.Richardson Marcela Celis Boris Villanueva Adriana Sanchez Programa de Biología Facultad de Ciencias NaturalesUniversidad del RosarioBogotaD.C.Colombia Subdireccion Científica Jardín Botanico de Bogota“Jose Celestino Mutis”BogotaD.C.Colombia Independent Researcher BogotaD.C.Colombia Tropical diversity Section Royal Botanic Garden EdinburghUK School of Biological Earth and Environmental SciencesUniversity College CorkCorkIreland departamento de Química y Biología Universidad del NorteKm.5 Vía Puerto ColombiaArea Metropolitana de Barranquilla 081007Colombia

data gaps and biases are two important issues that affect the quality of biodiversity information and downstream results.Understanding how best to fill existing gaps and account for biases is necessary to improve our current information most effectively.Two current main approaches for obtaining and improving data include(1)curation of biological collections,and(2)fieldwork.However,the comparative effectiveness of these approaches in improving biodiversity data remains little explored.We used the Flora de Bogota project to study the magnitude of change in species richness,spatial coverage,and sample coverage of plant records based on curation versus fieldwork.The process of curation resulted in a decrease in species richness(synonym and error removal),but it significantly increased the number of records per species.Fieldwork contributed to a slight increase in species richness,via accumulation of new records.Additionally,curation led to increases in spatial coverage,species observed by locality,the number of plant records by species,and localities by species compared to fieldwork.Overall,curationwas more efficient in producing new information compared to fieldwork,mainly because of the large number of records available in herbaria.We recommend intensive curatorial work as the first step in increasing biodiversity data quality and quantity,to identify bias and gaps at the regional scale that can then be targeted with fieldwork.The stepwise strategy would enable fieldwork to be planned more costeffectively given the limited resources for biodiversity exploration and characterization.

关键词： Colombia Flora de Bogota Sample coverage Species richness Tropical Andes

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