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GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： william r.swindell Krzysztof Bojanowski Mark S.Kindy raymond M.W.Chau Dorothy Ko Heritage College of Osteopathic Medicine Ohio UniversityAthensOHUSA Sunny BioDiscovery IncSanta PaulaCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAMC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALS)is currently an incurable disease without highly effective pharmacological *** peptide drug GM604(GM6 or Alirinetide)was developed as a candidate ALS therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used rNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment(6,24 and 48 h).results:We identified 2867 protein-coding genes with expression significantly altered by GM6(FDrrly(6 h)responses included up-regulation of Notch and hedgehog signaling components,with increased expression of developmental genes mediating neurogenesis and axon *** GM6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mrNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes(STAT3,HOXD11,HES7,GLI1).We identified 77 ALS-associated genes with expression significantly altered by GM6 treatment(FDrre known to function in neurogenesis,axon guidance and the intrinsic apoptosis ***:Our findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECM modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： Alzheimer’s disease Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s disease Neurodegenerative disease Notch,Parkinson’s disease rNA-seq Transcriptome

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Unique domain appended to vertebrate trNA synthetase is essential for vascular development

Unique domain appended to vertebrate tRNA synthetase is esse...

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第十七届国际生物物理大会;第十二届中国生物物理大会

作者： Eric C swindell Alan G Marshall Shuji Kishi Department of Pediatrics The University of Texas Medical School at Houston6431 Fannin StreetHoustonTX 77030 Department of Chemistry & Biochemistry Florida State University95 Chieftain WayTallahasseeFL 32306USA Department of Metabolism and Aging The Scripps Research Institute130 Scripps WayJupiterFL 33458USA

During evolution,cytoplasmic aminoacyl-trNA synthetases progressively added novel domains that were timed to specific developments.A recently identified example is the UNE-S domain,appended to seryl-trNA synthetase(SerrS) in species that developed closed circulatory *** genetic studies have established an essential role for SerrS in VEGFA-linked vascular *** a combination of

关键词： minoacyl-trNA synthetases Zebrafish nuclear localization signal vascular development

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优化FTTH网络的光纤无源设施

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电子设计技术 2003年第11期10卷 102-102,104页

作者： Guy swindell Leonard ray AFLTelecommunications Corning Optical Fiber

FTTH曾经被视为梦想,但它作为一种可行的接入方案现在正在获得发展的动力。

关键词： FTTH 光分支器光纤光导纤维无源

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Quality of Life in Men Treated for Early Prostate Cancer: A Prospective Patient Preference Cohort Study

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Journal of Cancer Therapy 2011年第4期2卷 448-457页

作者： Carmel Nirupa Anandadas Susan Elizabeth Davidson Noel william Clarke Stephen Charles william Brown John Paul Logue Lynne Gilmore richard swindell Gerald Nicholas Collins Patrick Henry O’reilly Guy David Wemyss-Holden Maurice Waiming Lau Pradip Madhukar Javle Vijay Alini Chandi ramani richard James Brough James Pinson Wylie richard Andrew Cowan 不详

Objectives: In 1997, a study was launched to investigate the treatment of early prostate cancer. Using a patient preference design, health-related quality-of-life (HrQOL) and disease specific HrQOL was assessed prospectively to compare men undergoing radical prostatectomy (rP), hypo-fractionated conformal radiotherapy (CrT) or brachytherapy (BT). Methods: Patients with localised prostate cancer were counselled by a urological surgeon, clinical oncologist and specialist uro-oncology nurse. Patients received treatment according to individual preference. 430 men chose and received rP (n = 217), CrT (n = 161) and BT (n = 52). 354 (82%) completed pre-treatment rAND 36-Item Short-Form Health survey version-2 (SF36v2) and University of California, Los Angeles Prostate cancer index (UCLA-PCI) questionnaires. HrQOL score changes from baseline to 24 months were compared using Kruskall-Wallis test. results: Pre-treatment, the CrT cohort scored lower for physical function (p = 0.0029) and general health perception (p = 0.0021). The BT cohort reported better baseline scores for urinary function (p = 0.0291), urinary bother (p = 0.0030), sexual function (p = 0.0009) and bowel bother (p = 0.0063). At 24 months, bowel function was similar for CrT and BT but both modalities were worse than rP (p = 0.0010). Urinary continence deteriorated most following rP (p rse urinary bother (p = 0.0153). Sexual function deteriorated most following rP and BT (p rcentages of patients achieving erections adequate for sexual activity (from baseline to 24 months) were 66% to 29% for rP, 62% to 49% for CrT and 88% to 65% for BT. Conclusion: This data demonstrates significant differences in disease specific quality-of-life between rP, CrT and BT and should be available for men with early prostate cancer making treatment decisions.

关键词： Early Prostate Cancer Quality of Life Patient Preference Prostatectomy Hypo-Fractionated radiotherapy Brachytherapy

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超声波断层照相扫描器

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国外医学（生物医学工程分册） 1993年第3期16卷 155-157页

作者： Stytz M r 徐振耀沈奇

七十年代X线计算机辅助断层照相术的诞生为研制使用其它形式辐射的其它高技术成像方法开辟了一条金光大道。由Barrett和swindell”、Fleischer和James、Greenleaf、Hill、Kristoffersen和Angel-son、NcDicken、Meyers、robinson和Greenl... 详细信息

关键词：超声波断层照相扫描器

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