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Intravenous immune globulin suppresses angiogenesis in mice and humans

Signal Transduction and Targeted Therapy 2016年第1期1卷 141-148页

作者： Reo Yasuma Valeria Cicatiello Takeshi Mizutani Laura Tudisco Younghee Kim Valeria Tarallo Sasha Bogdanovich Yoshio Hirano nagaraj kerur Shengjian Li Tetsuhiro Yasuma Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Balamurali K Ambati Sevim Barbasso Helmers Ingrid E Lundberg Ondrej Viklicky Jeanette HW Leusen J Sjef Verbeek Bradley D Gelfand Ana Bastos-Carvalho Sandro De Falco Jayakrishna Ambati Department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA Department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly Department of Physiology University of KentuckyLexingtonKYUSA Department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CEINGE—Biotecnologie Avanzate s.c.ar.l.NaplesItaly Department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA Department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Rheumatology Unit Department of MedicineKarolinska InstitutetKarolinska University HospitalStockholmSweden Department of Nephrology Institute for Clinical and Experimental MedicinePrague 4Czech Republic Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands Department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands Department of Biomedical Engineering University of KentuckyLexingtonKYUSA Department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly

Human intravenous immune globulin(IVIg),a purified IgG fraction composed of~60%IgG1 and obtained from the pooled plasma of thousands of donors,is clinically used for a wide range of *** biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG(IgG)Fc ***,we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI,a high-affinity receptor for *** we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases,namely,neovascular age-related macular degeneration,corneal neovascularization,colorectal cancer,fibrosarcoma and peripheral arterial ischemic *** was mediated by the Fc region of IVIg,required FcγRI and had similar potency in transgenic mice expressing human Fcγ***,IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel *** data place IVIg,an agent approved by the US Food and Drug Administration,as a novel angioinhibitory drug in doses that are currently administered in the clinical *** addition,they raise the possibility of an unintended effect of IVIg on blood vessels.

关键词： doses inhibited degeneration

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Human IgG1 antibodies suppress angiogenesis in a target-independent manner

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Signal Transduction and Targeted Therapy 2016年第1期1卷 158-171页

作者： Sasha Bogdanovich Younghee Kim Takeshi Mizutani Reo Yasuma Laura Tudisco Valeria Cicatiello Ana Bastos-Carvalho nagaraj kerur Yoshio Hirano Judit Z Baffi Valeria Tarallo Shengjian Li Tetsuhiro Yasuma Parthasarathy Arpitha Benjamin J Fowler Charles B Wright Ivana Apicella Adelaide Greco Arturo Brunetti Menotti Ruvo Annamaria Sandomenico Miho Nozaki Ryo Ijima Hiroki Kaneko Yuichiro Ogura Hiroko Terasaki Balamurali K Ambati Jeanette HW Leusen Wallace Y Langdon Michael R Clark Kathryn L Armour Pierre Bruhns J Sjef Verbeek Bradley D Gelfand Sandro De Falco Jayakrishna Ambati Department of Ophthalmology and Visual Sciences University of KentuckyLexingtonKYUSA Department of Ophthalmology and Visual Science Nagoya City University Graduate School of Medical SciencesNagoyaJapan Department of Ophthalmology Nagoya University Graduate School of MedicineNagoyaJapan Angiogenesis Lab Institute of Genetics and Biophysics—CNRNaplesItaly Bio-Ker MultiMedica GroupNaplesItaly Department of Advanced Biomedical Sciences University of Naples‘Federico II’NaplesItaly CEINGE—Biotecnologie Avanzate s.c.a.r.l.NaplesItaly Istituto di Biostrutture e Bioimmagini CNRNaplesItaly Department of Ophthalmology and Visual Sciences Moran Eye CenterUniversity of Utah School of MedicineSalt Lake CityUTUSA Department of Ophthalmology Veterans Affairs Salt Lake City Healthcare SystemSalt Lake CityUTUSA Immunotherapy Laboratory Laboratory for Translational ImmunologyUniversity Medical Center UtrechtUtrechtThe Netherlands School of Pathology and Laboratory Medicine University of Western AustraliaCrawleyWAAustralia Division of Immunology Department of PathologyUniversity of CambridgeCambridgeUK Department of Immunology Unit of Antibodies in Therapy and PathologyInstitut PasteurParisFrance Institut National de la Santéet de la Recherche Médicale(INSERM)U1222 ParisFrance Department of Human Genetics Leiden University Medical CenterLeidenThe Netherlands Department of Biomedical Engineering University of KentuckyLexingtonKYUSA Department of Microbiology Immunologyand Molecular GeneticsUniversity of KentuckyLexingtonKYUSA IRCCS MultiMedica MilanoItaly Department of Physiology University of KentuckyLexingtonKYUSA.

Aberrant angiogenesis is implicated in diseases affecting nearly 10%of the world’s *** most widely used antiangiogenic drug is bevacizumab,a humanized IgG1 monoclonal antibody that targets human *** bevacizumab does not recognize mouse Vegfa,it inhibits angiogenesis in *** we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI(CD64)and c-Cbl,impairing macrophage *** approved humanized or human IgG1 antibodies without mouse targets(adalimumab,alemtuzumab,ofatumumab,omalizumab,palivizumab and tocilizumab),mouse IgG2a,and overexpression of human IgG1-Fc or mouse IgG2a-Fc,also inhibited angiogenesis in wild-type and FcγR humanized *** anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown,Fc cleavage,IgG-Fc inhibition,disruption of Fc-FcγR interaction,or elimination of FcRγ-initated ***,bevacizumab’s Fc region potentiated its anti-angiogenic activity in humanized VEGFA ***,mice deficient in FcγRI exhibited increased developmental and pathological *** findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.

关键词： CD64 angiogenesis antibodies

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ZrOCl2 Catalysed Chemoselective Conversion of Aldehydes to geminal-Diacetates and Their Cleavage： A Mild and Efficient Method

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Chinese Journal of Chemistry 2007年第10期25卷 1555-1558页

作者： nagaraj, Adki SANJEEVA REDDY, Cherkupally Department of Chemistry Kakatiya University Warangal-506 009 India

ZrOCl2 was found to be an effective Lewis acid catalyst for the solventless chemoselective conversion of aldehydes into geminal-diacetates in high yields at room temperature. Regeneration of the aldehydes from the acetals was also achieved using the same catalyst in water. The beneficial effect of microwave irradiation on the reaction was also described. Other advantages are the very low loading of catalyst, high yields achieved even on a gram scale, and considerably shortened reaction time compared to the conventional method.

关键词： zirconium oxychloride acetal chemoselective microwave irradiation

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Knoevenagel condensation of α,β-unsaturated aromatic aldehydes with barbituric acid under non-catalytic and solvent-free conditions

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Chinese Chemical Letters 2007年第12期18卷 1431-1435页

作者： Cherkupally Sanjeeva Reddy Adki nagaraj Department of Chemistry Kakatiya UniversityWarangal 506009India

An efficient route for the synthesis of 5-（arylpropenylidine）-2,4,6-pyrimidinetrione 3 from an appropriate α,βunsaturated aromatic aldehydes 1 and barbituric acid 2 under both non-catalytic and solvent-free microwave irradiation conditions was described. In this way, a range of biologically important compounds 3 was obtained in good to excellent yields （86-98%） in a very short reaction time （30-80 s）.

关键词： Barbituric acid Knoevenagel condensation 5-(Arylpropenylidine)-2,4,6-pyrimidinetrione

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Zirconyl chloride promoted highly efficient solid phase synthesis of amide derivatives

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Chinese Chemical Letters 2007年第10期18卷 1213-1217页

作者： Cherkupally Sanjeeva Reddy Adki nagaraj Pochampally Jalapathi Department of Chemistry Kakatiya UniversityWarangal 506009India

An efficient solid phase route for the synthesis of amide derivatives by the reaction of carboxylic acids with urea in the presence of catalytic amount of zirconyl chloride under microwave irradiation conditions was described. In this way, a range of interesting amide derivatives was obtained in good to excellent yields. The catalyst was recycled with fresh reactants and it gave almost similar results without significant loss of activity up to the third run.

关键词： Carboxylic acids Urea Zircony chloride Solid phase Amides Recyclable catalyst

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Evaluation of electrochemical impedance and biocorrosion characteristics of as-cast and T4 heat treated AZ91 Mg-alloys in Ringer’s solution

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Journal of Magnesium and Alloys 2019年第1期7卷 134-143页

作者： nagaraj M.Chelliah Pambannan Padaikathan Ram Kumar Department of Metallurgical Engineering PSG College of TechnologyCoimbatore 641004Tamil NaduIndia Department of Materials Engineering Indian Institute of ScienceBangalore 560012KarnatakaIndia Department of Mechanical Engineering Indian Institute of TechnologyRupnagar 140001PunjabIndia

The present study aims at understanding the electrochemical impedance and biocorrosion characteristics of AZ91 Mg-alloy in Ringer’s ***-cast AZ91 Mg-alloy was subjected to T4 heat treatment in a way to homogenize its microstructure by dissolving most of theβ-Mg 17 Al 12 phase at the vicinity of grain *** electrochemical impedance and biocorrosion performances of these two different microstructures(as-cast and T4 heat treated AZ91 Mg-alloys)in Ringer solution were evaluated by electrochemical impendence spectroscopy,potentiodynamic polarization and weight loss *** spectra showed that both microstructures exhibit similar dynamic response as a function of the immersion time;however,the value of impedance and maximum phase angle are about 50%higher in as-cast AZ91 Mg-alloy as compared to that of homogenized AZ91 *** loss measurement indicated that corrosion resistance of as-cast AZ91 was significantly better than that of homogenized *** and XRD analysis revealed that as-cast AZ91 contains a passive film of MgCO_(3)and CaCO_(3)precipitates with near spherical morphologies,whereas homogenized AZ91 comprised mainly unstable Mg(OH)_(2)film featured by irregular plate-like morphologies.

关键词： Mg-alloys Ringers solution Homogenization Corrosion Electrochemical impedance Spectroscopy(EIS) Weight loss

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Development and validation of Hyperacusis Handicap Questionnaire in individuals with tinnitus associated with hyperacusis

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Journal of Otology 2020年第4期15卷 124-128页

作者： Prashanth Prabhu Megha Kondli nagaraj All India Institute of Speech and Hearing ManasagangothriMysuru570006India

Introduction:Hypersensitivity to sound and tinnitus are often co-morbid and can influence emotional well-being,hearing,sleep,concentration,cause anxiety,and interfere with speech perception in ***:A clear measure of sensitivity to sound is important as there is dearth in standard protocol for evaluating hyperacusis in individuals with *** there are a few questionnaires to assess hyperacusis,a direct application of these questionnaires in the Indian context would be ***:The study attempts to develop and validate an indigenous Hyperacusis Handicap Questionnaire(HHQ)for individuals with tinnitus associated with ***:A total of 25 questions were considered for ***,21 questions were subdivided into three sections of seven questions each,tapping,‘Functional,’‘Social,’and‘Emotional’aspects of the *** was administered on 77 individuals with tinnitus associated with hyperacusis in the age range of 20e55 years for further validation.A total score was obtained by adding all the three ***:The internal consistency of the questionnaire was determined by Cronbach’s Alpha(a)was a?0.85;and,a?0.83 for Functional,a?0.81 for Social,a?0.7 for Emotional subscales suggesting that the questionnaire can be used for the assessment of handicap associated with hyperacusis in individuals with ***,no significant difference in terms of gender and duration of tinnitus comparisons were ***:The obtained results suggest that HHQ will aid in the characterization and quantification of the handicap associated with hyperacusis in individuals with tinnitus.

关键词： Quality of life Annoyance Reduced tolerance Hypersensitivity

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Study of material removal behavior on R-plane of sapphire during ultra-precision machining based on modified slip-fracture model

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Nanotechnology and Precision Engineering 2020年第3期3卷 141-155页

作者： Suk Bum Kwon Aditya nagaraj Hae-Sung Yoon Sangkee Min Department of Mechanical Engineering University of Wisconsin-Madison1513 University AvenueMadisonWI 53706United States of America School of Aerospace and Mechanical Engineering Korea Aerospace University76 Hanggongdaehak-roDeogyang-guGoyang-siGyeonggi-do 10540Republic of Korea

In this paper, the modified slip/fracture activation model has been used in order to understand the mechanism of ductile-brittle transition on the R-plane of sapphire during ultra-precision machining by reflecting direction of resultant force. Anisotropic characteristics of crack morphology and ductility of machining depending on cutting direction were explained in detail with modified fracture cleavage and plastic deformation parameters. Through the analysis, it was concluded that crack morphologies were mainly determined by the interaction of multiple fracture systems activated while, critical depth of cut was determined by the dominant plastic deformation parameter. In addition to this, by using proportionality relationship between magnitude of resultant force and depth of cut in the ductile region, an empirical model for critical depth of cut was developed.

关键词： Ductile-brittle transition Crack morphology Single crystal sapphire Deformation mechanism Orthogonal cutting Ultra-precision machining

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2D-titanium carbide(MXene)based selective electrochemical sensor for simultaneous detection of ascorbic acid,dopamine and uric acid

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Journal of Materials Science & Technology 2021年第13期72卷 122-131页

作者： nagaraj Murugan Rajendran Jerome Murugan Preethika Anandhakumar Sundaramurthy Ashok K.Sundramoorthy Department of Chemistry SRM Institute of Science and TechnologyKattankulathur603203Tamil NaduIndia SRM Research Institute SRM Institute of Science and TechnologyKattankulathur603203Tamil NaduIndia

Two-dimensional(2 D)titanium carbide(MXene)nanosheets exhibited excellent conductivity,flexibility,high volumetric capacity,hydrophilic surface,thermal stability,***,it has been exploited in various ***,we report synthesis of mixed phase 2 D MXene as a catalytic material for simultaneous detection of important biomolecules such as ascorbic acid(AA),dopamine(DA)and uric acid(UA).Crystalline structure,surface morphology and elemental composition of mixed phase titanium carbide(Ti-C-T_(x))MXene(T_(x)=-F,-OH,or-O)nanosheets were confirmed by X-ray diffraction(XRD),Raman spectroscopy,high-resolution transmission electron microscopy(HR-TEM),high-re solution scanning electron microscopy(HR-SEM)and Energy-dispersive X-ray spectroscopy(EDS)mapping ***,Ti-C-T_(x) modified glassy carbon electrode(GCE)was prepared and its electrochemical properties are studied by cyclic voltammetry(CV)and diffe rential pulse voltammetry(DPV).It was found that Ti-C-T_(x) modified GCE(Ti-C-T_(x)/GCE)showed excellent electrocatalytic activity and separated oxidation peaks of important biomolecules such as AA(at 0.01 V),DA(at 0.21 V)and UA(at 0.33 V).Also,Ti-C-T_(x)/GCE sensor is enabled their simultaneous detection in physiological pH from 100 to 1000μM for AA,0.5-50μM for DA and 0.5-4μM&100-1500μM for *** limit of detection’s(LOD)was estimated as 4.6μM,0.06μM and 0.075μM for AA,DA and UA,***,real sample analysis indicated that spiked AA,DA and UA can be determined accurately by Ti-C-T_(x)/GCE with the recovery ratio in the range between 100.5%-103%in human urine *** proposed Ti-C-T_(x) modified electrode exhibited good stability,selectivity and reproducibility as an electrochemical sensor for the detection of AA,DA and UA molecules.

关键词： Titanium carbide Dopamine Uric acid Ascorbic acid Electrochemical sensor

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Smart Grid Communication Under Elliptic Curve Cryptography

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Intelligent Automation & Soft Computing 2023年第5期36卷 2333-2347页

作者： B.Prabakaran T.R.Sumithira V.nagaraj Mahendra Engineering College Salem637503TamilnaduIndia Government College of Engineering Salem636011TamilnaduIndia Knowledge Institute of Technology Salem637504TamilnaduIndia

Smart Grids(SGs)are introduced as a solution for standard power *** signiﬁcant capabilities of smart grids help to monitor consumer behaviors and power ***,the delay-sensitive network faces numer-ous challenges in which security and privacy gain more *** to trans-mitted messages,control over smart grid information and user privacy are the major concerns in smart grid *** secure communication between the service provider and the user is the only possible solution for these security ***,this research work presents an efﬁcient mutual authentication and key agreement protocol for smart grid communication using elliptic curve crypto-graphy which is robust against security threats.A trust authority module is intro-duced in the security model apart from the user and service provider for *** proposed approach performance is veriﬁed based on different security features,communication costs,and computation *** comparative analysis of experimental results demonstrates that the proposed authentication model attains better performance than existing state of art of techniques.

关键词： Smart grid elliptic curve cryptography key management mutual authentication

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