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Double negative T cells,a potential biomarker for systemic lupus erythematosus

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Precision Clinical Medicine 2020年第1期3卷 34-43页

作者： jessy j.alexander alexander jacob Anthony Chang Richard j.Quigg james N.jarvis Department of Pathology University of ChicagoChicagoIL 60637USA Departments of Medicine PediatricsJacobs School of Medicine and Biomedical Sciences and GeneticsGenomics&Bioinformatics ProgramUniversity at BuffaloBuffaloNY 14203USA

Systemic lupus erythematosus(SLE)is an autoimmune disease that is a challenge to diagnose and *** is an urgent need for biomarkers to help define organ involvement,and more effective therapies.A unique population of T cells,the CD3^(+)CD4^(−)CD8^(−)(DNeg)cells,is significantly increased in lupus *** cases(53%)of pediatric SLE patients had elevated DNeg cells in their peripheral blood,which correlated with kidney function(R^(2)=0.54).Significant infiltration of DNeg cells was observed in both adult and pediatric lupus kidneys by *** the first time,this study provides direct evidence that DNeg cells facilitate kidney injury in preclinical 8-week-old MRL/lpr lupus *** lupus mice,the increase in DNeg cells tracked with worsening disease and correlated with kidney function(R^(2)=0.85).Our results show that DNeg cells per se can cause kidney dysfunction,increase in number with increase in disease pathology,and could serve as a potential biomarker.

关键词： CD3^(+)CD4^(−)CD8^(−)T cells glomerulonephritis inflammation lupus

Effect of lymphotoxin blockage on different stages of Sjogren's syndrome in an animal model

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Rheumatology & Autoimmunity 2022年第2期2卷 76-81页

作者： alexander jacob Long Shen jing He Kelly Nealon jessy j.alexander julian L.Ambrus jr Department of Medicine SUNY at Buffalo School of MedicineBuffaloNew YorkUSA Department of Rheumatology and Immunology Peking University People's HospitalBeijingChina

Background:Lymphotoxin(LT)is an important mediator in Sjogren's syndrome(SS),both in patients and in animal *** of the LT alpha gene prevented the development of disease manifestations in the interelukin alpha transgenic mouse(IL14αTG)mouse model of ***:The current study was designed to evaluate the use of LT inhibitors at different stages of the disease in IL14αTG *** and Methods:IL14αTG mice were treated with anti‐LTa monoclonal antibody,LTb receptor‐immunoglobulin fusion protein(LTBR‐Ig)or isotype control during different stages of disease and analysis of salivary gland function,immunoglobulins,autoantibodies and histology of internal organs *** and Discussion:The inhibitors were very effective in maintaining salivary gland function and preventing infiltration of the glands with lymphocytes when used in the early stages of the *** LT at later stages of the disease did not recover salivary gland function but was still effective in limiting extra glandular manifestations including eye disease and tumor *** differences were noted in the effectiveness of anti‐LTαversus LTBR‐Ig in limiting particular disease ***:LT inhibitors deserve further investigation in the management of SS at whatever stage is identified.

关键词： animal model lymphotoxin Sjogren's syndrome

Effect of arsenic contaminated irrigation water on Lens culinaris *** toxicity assessment using lux marked biosensor

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journal of Environmental Sciences 2012年第6期24卷 1106-1116页

作者： F.R.Sadeque Ahmed Ian j.alexander Mwinyikione Mwinyihija Ken Killham Department of Environment (Climate Change) E-16 AgargaonDhakaBangladesh School of Biological Sciences Institute of Biological and Environmental SciencesUniversity of AberdeenAberdeenAB24 3UUUK Kenya Leather Development Council P.O.Box 14480NairobiKenya Remedios Limited Balgownie Technology CentreCampus 3 Balgownie DriveAberdeenAB22 8GWUK

Contamination of irrigation water represents a major constraint to Bangladesh agriculture,resulting in elevated levels in the terrestrial *** bacterial biosensor technology has previously been used to measure the toxicity of metals in various environmental *** arbuscular mycorrhizal fungi have their most significant effect on phosphorus uptake,but showed alleviated metal toxicity to the host *** study examined the effects of arsenic and inoculation with an arbuscular mycorrhizal fungus,Glomus mosseae,on lentil （Lens culinaris ***）.Plants were grown with and without arbuscular mycorrhizal inoculum for 9 weeks in a sand and terra-green mixture （50：50,V/V） and watered with five levels of arsenic （0,1,2,5,10 mg As/L arsenate）.The results showed that arsenic addition above 1 mg/L significantly reduced percentage of mycorrhizal root *** further analysis a close relationship was established with the vegetative and reproductive properties of lentil （***） plants compared to the percentage bioluminescence of the soil ***,arbuscular mycorrhizal fungal inoculation reduced arsenic concentration in roots and *** concentrations of arsenic （5,10 mg As/L arsenate） reduced the mycorrhizal efficiency to increase phosphorus content and nitrogen ***,this study showed that increased concentration of arsenic in irrigation water had direct implications to the lentil （***） plants overall *** the use of bioassay demonstrated that mycorrhiza and clay particle reduced arsenic bioavailability in soil.

关键词： bioassay contaminated water lentil trace metals vegetative response

Optical coherence tomography in optic disc drusen

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Annals of Eye Science 2020年第1期5卷 22-34页

作者： j.alexander Fraser Lulu L.C.D.Bursztyn Department of Clinical Neurological Sciences Western UniversityLondonONCanada Department of Ophthalmology Western UniversityLondonONCanada

Optic disc drusen (ODD) are hyaline deposits in the optic nerve head, occurring in approximately 2% of the population. ODD may be superficial and visible, or buried and either invisible or seen only as elevation of the optic disc, mimicking optic disc edema. Advanced optic nerve imaging, including optical coherence tomography (OCT) can be used to diagnose and characterize ODD with very high resolution. Enhanced depth imaging (EDI-OCT) in particular has emerged as the optimal modality to directly visualize ODD. This modality has led to a greater ability to differentiate ODD from optic disc edema and prevent misdiagnosis or invasive testing. We review the characteristic findings of ODD on OCT, their distinguishing features, and the use of OCT as a biomarker in the neuro-ophthalmic assessment of ODD.

关键词： Drusen optic disk tomography optical coherence

A Company Presents Itself to the World

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journal of Literature and Art Studies 2023年第10期13卷 803-811页

作者： Richard j.alexander Vienna University of Business and Economics ViennaAustria

As we all know,environmental breakdown is rooted in capitalism’s quest for perpetual *** to O’Connor(quoted in Büscher et al 2010/2013,p.3)the“environmental crisis has given liberal capitalist society a new lease on life.”He continues:“Now,through purporting to take in hand the saving of the environment,capitalism invents a new legitimation for itself:the sustainable and rational use of nature”.“Those who hold the power and they are not all heads of state,see themselves as saviours of the world,and offer the population the opportunity of becoming their clients”is how john Berger has referred to such cognitive *** discourse analysis and corpus linguistics are employed to scrutinize a powerful corporation’s *** company produces and distributes food *** story it presents to the world maintains that it protects animal welfare,the environment and people,among other things,in all its *** language it employs on its corporate websites will be subjected to close analysis.

关键词： agribusiness discourse analysis ecolinguistics greenwashing sustainability

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 *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** 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 *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** 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 *** 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 *** 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 *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

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

Subnanometer localization accuracy in widefield optical microscopy

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Light(Science & Applications) 2018年第1期7卷 740-754页

作者： Craig R.Copeland jon Geist Craig D.McGray Vladimir A.Aksyuk j.alexander Liddle B.Robert Ilic Samuel M.Stavis Center for Nanoscale Science and Technology National Institute of Standards and TechnologyGaithersburgMD 20899USA Maryland NanoCenter University of MarylandCollege ParkMD 20742USA Engineering Physics Division National Institute of Standards and TechnologyGaithersburgMD 20899USA

The common assumption that precision is the limit of accuracy in localization microscopy and the typical absence of comprehensive calibration of optical microscopes lead to a widespread issue—overconfidence in measurement results with nanoscale statistical uncertainties that can be invalid due to microscale systematic *** this article,we report a comprehensive solution to this underappreciated *** develop arrays of subresolution apertures into the first reference materials that enable localization errors approaching the atomic scale across a submillimeter *** present novel methods for calibrating our microscope system using aperture arrays and develop aberration corrections that reach the precision limit of our reference *** correct and register localization data from multiple colors and test different sources of light emission with equal accuracy,indicating the general applicability of our reference materials and calibration *** a first application of our new measurement capability,we introduce the concept of critical-dimension localization microscopy,facilitating tests of nanofabrication processes and quality control of aperture *** a second application,we apply these stable reference materials to answer open questions about the apparent instability of fluorescent nanoparticles that commonly serve as fiducial *** study establishes a foundation for subnanometer localization accuracy in widefield optical microscopy.

关键词： optical limit field

Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor

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Cellular & Molecular Immunology 2016年第5期13卷 651-657页

作者： jessy j. alexander Lee D. Chaves Anthony Chang Shruti Dighe alexander jacob Richard j. Quigg Division of Nephrology Department of Medicine University at Buffalo School of Medicine and Health Sciences Buffalo NY USA Department of Pathology The University of Chicago Chicago IL USA Correspondence: Dr Jessy J. Alexander Division of Nephrology State University of New York at Buffalo Clinical and Translational Research Center 875 Ellicott Street 8-022 Buffalo NY 14203 USA

Activation of complement generates C5a which leads to signaling through C5aR 1. This is tightly controlled, including by the plasma proteins factor H （FH） and carboxypeptidase N. Here we studied a chronic serum sickness （CSS） model of glomerulonephritis （GN） in which there is an active humoral immune response, formation of glomerular immune complexes （ICs）, and resulting glomerular inflammation. The antibody response, glomerular IC deposition, the degree of GN, and consequent renal functional insufficiency in CSS were all worse in FH-/- mice compared to wild-type FH＋/＋ animals. This was ameliorated in the former by giving a C5aR1 antagonist for the final 3 weeks of the 5-week protocol. In contrast, blocking CP-mediated inactivation of C5a increased these disease measures. Thus, complement regulation by both plasma FH and CP to limit the quantity of active C5a is important in conditions where the humoral immune response is directed to a continuously present foreign antigen. Signaling through C5aR1 enhances the humoral immune response as well as the inflammatory response to ICs that have formed in glomeruli. Both effects are relevant even after disease has begun. Thus, pharmacological targeting of C5a in IC-mediated GN has potential clinical relevance.

关键词： C5a carboxypeptidase N factor H glomerulonephritis

Measuring user preferences and behaviour in a topographic immersive virtual environment(TopoIVE)of 2D and 3D urban topographic data

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International journal of Digital Earth 2021年第12期14卷 1835-1867页

作者： Łukasz Halik alexander j.Kent Department of Cartography and Geomatics Adam Mickiewicz UniversityPoznańPoland School of Psychology and Life Sciences Canterbury Christ Church UniversityCanterburyUK

This paper investigates user preferences and behaviour associated with 2D and 3D modes of urban representation within a novel Topographic Immersive Virtual Environment(TopoIVE)created from official 1:10,000 *** participants were divided into two groups:the first were given a navigational task within a simulated city and the second were given the freedom to explore it.A Head-Mounted Display(HMD)Virtual Reality(VR)app allowed participants to switch between 2D and 3D representations of buildings with a remote controller and their use of these modes during the experiment was *** performed mental rotation tests before entering the TopoIVE and were interviewed afterwards about their experiences using the *** results indicate that participants preferred the 3D mode of representation overall,although preference for the 2D mode was slightly higher amongst those undertaking the navigational task,and reveal that different wayfinding solutions were adopted by participants according to their ***,the findings suggest that users exploit different aspects of 2D and 3D modes of visualization in their wayfinding strategy,regardless of their *** potential to combine the functionality of 2D and 3D modes therefore offers substantial opportunities for the development of immersive virtual reality products derived from topographic datasets.

关键词： Virtual reality(VR) immersive virtual environment(IVE) 2D versus 3D wayfinding topographic data