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Fibroblast growth factor receptor 3 effects on proliferation and telomerase activity in sheep growth plate chondrocytes

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Journal of Animal Science and Biotechnology 2013年第1期4卷 41-48页

作者： Logan B Smith Janelle m Belanger anita m oberbauer Department of Animal Science University of California

Background： Fibroblast growth factor receptor 3 （FGFR3） inhibits growth-plate chondrocyte proliferation and limits bone elongation. Gain-of-function FGFR3 mutations cause dwarfism, reduced telomerase activity and shorter telomeres in growth plate chondroyctes suggesting that FGFR3 reduces proliferative capacity, inhibits telomerase, and enhances senescence. Thyroid hormone （1-3） plays a role in cellular maturation of growth plate chondrocytes and a known target of T3 is FGFR3. The present study addressed whether reduced FGFR3 expression enhanced telomerase activity, mRNA expression of telomerase reverse transcriptase （TERT） and RNA component of telomerase （TR）, and chondrocyte proliferation, and whether the stimulation of FGFR3 by T3 evoked the opposite response. Results： Sheep growth-plate proliferative zone chondrocytes were cultured and transfected with siRNA to reduce FGFR3 expression; FGFR3 siRNA reduced chondrocyte FGFR3 mRNA and protein resulting in greater proliferation and increased TERT mRNA expression and telomerase activity （p 〈 0.0.5）. Chondrocytes treated with T3 significantly enhanced FGFR3 mRNA and protein expression and reduced telomerase activity （p 〈 0.05）; TERT and TR were not significantly reduced. The action of T3 at the growth plate may be partially mediated through the FGFR3 pathway. Conclusions： The results suggest that FGFR3 inhibits chondrocyte proliferation and reducing telomerase activity indicating an important role for telomerase in capacity during bone elongation. by down-regulating TERT expression sustaining chondrocyte proliferative

关键词： Chondrocytes Growth-plate Telomerase Fibroblast growth factor receptor 3 Thyroid hormone Sheep

Pitting and stress corrosion cracking studies on AISI type 316N stainless steel weldments

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Defence Technology（防务技术） 2018年第3期14卷 226-237页

作者： anita Toppo m.G.Pujar N.Sreevidya John Philip Corrosion Science and Technology Division Indira Gandhi Centre for Atomic Research materials Development and Technology Division Indira Gandhi Centre for Atomic Research

Pitting and stress corrosion cracking(SCC) studies on the 316 N stainless steel(SS) weldments in aswelded(AW) and thermally aged(solution annealing(SA), 550C/4 h and 750C/1 h) conditions were carried out in acidic and acidic chloride media. Pitting corrosion and SCC resistance was the highest for SA weldment, which was attributed to homogenization of microstructural and microchemical heterogeneities during solution annealing. SA specimen showed the most stable passive film as compared to AW weldment because of higher amount of delta-ferrite in AW weld metal, which resulted in an increased heterogeneity and inferior SCC resistance in AW. Stability of passive film was found to be adversely affected due to heat treatments(at 550C/4 h and 750C/1 h) because of the precipitation of carbide and sigma phases.

关键词：压力腐蚀不锈钢 AISI 焊接金属 SCC 稳定性氯化物微结构

Outdoor air pollution as a possible modifiable risk factor to reduce mortality in post-stroke population

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Neural Regeneration Research 2017年第3期12卷 351-353页

作者： anita Desikan milken Institute of Public Health George Washington UniversityWashingtonDCUSA

Outdoor air pollution is a known risk factor for mortality and *** type of air pollutant most reliably associated with disease is particulate matter（Pm）,especially finer particulate matter that can reach deeper into the lungs like Pm_（2.5）（particulate matter diameter 〈 2.5 μm）.Some subpopulations may be particularly vulnerable to Pm *** review focuses on one subgroup,long-term stroke survivors,and the emerging evidence suggesting that survivors of a stroke may be at a higher risk from the deleterious effects of Pm *** the mechanisms for mortality are still under debate,long-term stroke survivors may be vulnerable to similar mechanisms that underlie the well-established association between Pm pollution and cardiovascular *** fact that long-term stroke survivors of ischemic,but not hemorrhagic,strokes appear to be more vulnerable to the risk of death from higher Pm pollution may also bolster the connection to ischemic heart *** of an ischemic stroke may be more vulnerable to dying from higher concentrations of Pm pollution than the general *** clinical implications of this association suggest that reduced exposure to Pm pollution may result in fewer deaths amongst stroke survivors.

关键词： stroke particulate matter air pollution mortality ischemic stroke Pm2.5

Im-EDRD from Retinal Fundus Images Using multi-Level Classification Techniques

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Intelligent Automation & Soft Computing 2023年第1期35卷 567-580页

作者： m.P.Karthikeyan E.A.mary anita Department of Computer Science and Engineering R.M.K.Engineering CollegeChennai601206India Department of Computer Science and Engineering School of Engineering and TechnologyChrist UniversityBengaluru560029India

In recent years,there has been a significant increase in the number of people suffering from eye illnesses,which should be treated as soon as possible in order to avoid *** Fundus images are employed for this purpose,as well as for analysing eye abnormalities and diagnosing eye *** can be recognised as bright lesions in fundus pictures,which can be thefirst indicator of diabetic *** that in mind,the purpose of this work is to create an Integrated model for Exudate and Diabetic Retinopathy Diagnosis(Im-EDRD)with multi-level *** model uses Support Vector machine(SVm)-based classification to separate normal and abnormal fundus images at thefirst *** input pictures for SVm are pre-processed with Green Channel Extraction and the retrieved features are based on Gray Level Co-occurrence matrix(GLCm).Furthermore,the presence of Exudate and Diabetic Retinopathy(DR)in fundus images is detected using the Adaptive Neuro Fuzzy Inference System(ANFIS)classifier at the second level of *** detection,blood vessel extraction,and Optic Disc(OD)detection are all processed to achieve suitable ***,the second level processing comprises morphological Component Analysis(mCA)based image enhancement and object segmentation processes,as well as feature extraction for training the ANFIS classifier,to reliably diagnose ***,thefindings reveal that the proposed model surpasses existing models in terms of accuracy,time efficiency,and precision rate with the lowest possible error rate.

关键词： Retinal fundus images exudate diabetic retinopathy SVm ANFIS morphological component analysis

Proof-of-Improved-Participation:A New Consensus Protocol for Blockchain Technology

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Computer Systems Science & Engineering 2023年第3期44卷 2007-2018页

作者： N.anita m.Vijayalakshmi S.mercy Shalinie Thiagarajar College of Engineering Madurai625015India

The Internet of Things(IoT)is converting today’s physical world into a complex and sophisticated network of connected devices on an enormous *** existing malicious node detection mechanism in traditional approaches lacks in transparency,availability,or traceability of the detection *** overcome these concerns,we provide a decentralized technique using blockchain *** the fact that blockchain technology is applicable to create that type of models,existing harmony set of instructions are susceptible to do violence to such as DoS and Sybil,making blockchain systems ***,a new Proof-of-Improved-Participation(PoIP)harmony instruction was suggested that benefits the participation rules to select honest peers for mining while limiting malicious *** an evaluation the PoIP outperforms the Proof-of-Work(PoW)instructions are demonstrated,Proof of Stake(PoS)instructions in terms of energy consumption,accuracy,and *** compare the three consensus protocols with respect to efficiency,we build a lightweight mining model andfind that PoIP consensus has greater efficiency than PoW and *** has 25%lower attack risk than existing *** a consequence,our suggested methodology can provide the needed security with minimal attack risk and high accuracy,according to the analysis *** a result,suggested consensus is more efficient than existing methods in terms of block generation *** we suggest that suggested consensus is very suitable for IoT-based applications especially in healthcare.

关键词： Blockchain confidentiality proof-of-improved-participation consensus security

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Liver iron transport

World Journal of Gastroenterology 2007年第35期13卷 4725-4736页

作者： Ross m Graham anita CG Chua Carly E Herbison John K Olynyk Debbie Trinder School of medicine and Pharmacology Fremantle HospitalUniversity of Western AustraliaFremantleWestern AustraliaAustralia School of medicine and Pharmacology Fremantle HospitalUniversity of Western AustraliaFremantleWestern AustraliaAustralia Western Australian Institute for Medical ResearchNedlandsWestern AustraliaAustralia

The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors （TFRI and 2）, a ferrireductase （STEAP3）, the transporters divalent metal transporter-1 （DmT1） and ferroportin （FPN） as well as the haemochromatosis protein, HFE and haemojuvelin （HJV）, which are signalling molecules. many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.

关键词： Liver Iron homeostasis Iron uptake Iron release Iron transporters Hereditary haemochromatosis

Dynamic methylation driven by neuronal activity in hippocampal neurons impacts complex behavior

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Frontiers in Biology 2015年第5期10卷 439-447页

作者： anita E. Autry megumi Adachi Lisa m. monteggia Department of Neuroscience The University of Texas Southwestern Medical Center Dallas TX 75390-9070 USA

Epigenetic processes are well-known to play critical roles in learning and memory. Among epigenetic processes, accumulating data suggests that DNA methylation in particular is a critical determinant of learning and memory. In vitro data have suggested that DNA methyltransferase inhibitors can trigger DNA demethylation and subsequent gene expression of the brain-derived neurotrophic factor gene in an activity dependent manner. To examine if these processes occur in vivo, we chronically infused DNmT inhibitors into the hippocampus and examined the impact on behavior. We find that chronic DNmT inhibition in the hippocampus results in increased anxiety-related behavior and deficits in context-dependent fear conditioning accompanied by an increase in BDNF expression. Gene expression changes were blocked by pretreatment with the NmDA receptor antagonist AP5, suggesting that DNmT inhibition enhances gene expression in an activity-dependent manner and that, conversely, the behavior deficits and abnormal gene expression are facilitated by NmDA receptor activity.

关键词： DNA methylation NmDA receptors learning and memory behavior hippocampus

The Discovery and Development of Boceprevir:A Novel, First-generation Inhibitor of the Hepatitis C Virus NS3/4A Serine Protease

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Journal of Clinical and Translational Hepatology 2013年第1期1卷 22-32页

作者： anita Y. m. Howe Srikanth Venkatraman merck Sharp & Dohme Corp. Whitehouse Station NJ USA

An estimated 2–3%of the world's population is infected with hepatitis C virus (HCV), making it a major global health problem. Consequently, over the past 15 years, there has been a concerted effort to understand the pathophysiology of HCV infection and the molecular virology of replication, and to utilize this knowledge for the development of more effective treatments. The virally encoded non-structural serine pro-tease (NS3) is required to process the HCV polyprotein and release the individual proteins that form the viral RNA replication machinery. Given its critical role in the replication of HCV, the NS3 protease has been recognized as a potential drug target for the development of selective HCV therapies. In this review, we describe the key scientific discoveries that led to the approval of boceprevir, a first-generation, selective, small molecule inhibitor of the NS3 protease. We highlight the early studies that reported the crystal structure of the NS3 protease, its role in the processing of the HCV polyprotein, and the structural requirements critical for substrate clea-vage. We also consider the novel attributes of the NS3 protease-binding pocket that challenged development of small molecule inhibitors, and the studies that ultimately yielded milligram quantities of this enzyme in a soluble, tractable form suitable for inhibitor screening programs. Finally, we describe the discovery of boceprevir, from the early chemistry studies, through the development of high-throughput assays, to the phase Ⅲ clinical development program that ultimately provided the basis for approval of this drug. This latest phase in the development of boceprevir represents the culmination of a major global effort to under-stand the pathophysiology of HCV and develop small mole-cule inhibitors for the NS3 protease.

关键词： Biochemistry Synthesis Sustained virologic response

The pursuit of transplantation tolerance:new mechanistic insights

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Cellular & molecular Immunology 2019年第4期16卷 324-333页

作者： Pawan K.Gupta Christine m.mcIntosh anita S.Chong maria-Luisa Alegre Department of medicine The University of ChicagoChicagoIL 60637USA Department of Surgery The University of ChicagoChicagoIL 60637USA

Donor-specific transplantation tolerance that enables weaning from immunosuppressive drugs but retains immune competence to non-graft antigens has been a lasting pursuit since the discovery of neonatal *** recently,efforts have been devoted not only to understanding how transplantation tolerance can be induced but also the mechanisms necessary to maintain it as well as how inflammatory exposure challenges its *** review focuses on recent advances regarding key peripheral mechanisms of T cell tolerance,with the underlying hypothesis that a combination of several of these mechanisms may afford a more robust and durable tolerance and that a better understanding of these individual pathways may permit longitudinal tracking of tolerance following clinical transplantation to serve as *** review may enable a personalized assessment of the degree of tolerance in individual patients and the opportunity to strengthen the robustness of peripheral tolerance.

关键词： tolerance TCR avidity Treg T cell dysfunction