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81.
82.
Broggi J Joubert N Aucagne V Berteina-Raboin S Diez-Gonzalez S Nolan S Topalis D Deville-Bonne D Balzarini J Neyts J Andrei G Snoeck R Agrofoglio LA 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1391-1394
Hitherto unknown 1,4-disubstituted-[1,2,3]-triazolo-4',4'-dihydroxymethyl-3'-deoxy carbanucleosides were synthesized based on a "click approach." Various alkynes were introduced on a key azido intermediate by the "click" 1,3-dipolar Huisgen cycloaddition. Their antiviral activities and cellular toxicities were evaluated on vaccinia virus. None of the synthesized compounds exhibited a significant antiviral activity. 相似文献
83.
Roy V Kumamoto H Berteina-Raboin S Nolan SP Topalis D Deville-Bonne D Balzarini J Neyts J Andrei G Snoeck R Agrofoglio LA 《Nucleosides, nucleotides & nucleic acids》2007,26(10-12):1399-1402
With the commercial availability of well-defined ruthenium metathesis catalysts which combine high stability and broad functional group compatibility, olefin metathesis is now routinely integrated in various syntheses. We will report here the overwhelming power and scope of cross-metathesis in the area of new acyclic nucleoside phosphonates. Scope and limitations of this approach, and especially the E/Z stereocontrol, are discussed on selected examples from our drug discovery group. 相似文献
84.
Bett Nolan N. Hinch Scott G. Bass Arthur L. Braun Douglas C. Burnett Nicholas J. Casselman Matthew T. Cooke Steven J. Drenner S. Matthew Gelchu Ahmed Harrower William L. Ledoux Roxx Lotto Andrew G. Middleton Collin T. Minke-Martin Vanessa Patterson David A. Zhang Wenming Zhu David Z. 《Hydrobiologia》2022,849(2):385-405
Hydrobiologia - Many of the world’s rivers are dammed, altering the physiology, behaviour, ecology and survival of fish. Integrative research has the potential to improve our understanding of... 相似文献
85.
Dominguez Almela Victoria Nolan Emma T. Winter Emily R. Britton J. Robert 《Hydrobiologia》2022,849(10):2253-2265
Hydrobiologia - Native communities can resist the establishment and invasion of alien species through consumptive and/or competitive interactions. The extent of consumptive resistance from... 相似文献
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87.
D.G. Wilson N. Ahmed R. Nolan A. Frontera G. Thomas E.R. Duncan 《Indian pacing and electrophysiology journal》2015,15(1):4-14
AimsLimited data exist on outcomes in very elderly ICD recipients. We describe outcomes in new ICD and Cardiac Resynchronisation Therapy with Defibrillator (CRT-D) implants in octogenarians at our institution.MethodsPatients aged 80 years and above who underwent de novo ICD or CRT-D implantation from January 2006 to July 2012 were identified. Clinical data were collected from the procedural record, medical and ICD notes. Baseline characteristics were compared using independent sample t test for continuous variables and Fisher’s exact test for categorical variables. Kaplan-Meier curves were constructed.ResultsTen per cent of all new ICD/CRT-D implants were aged 80 years and over. Median age was 83.0 years. Median follow-up was 29 months. Death occurred in 17 (34%). Median time to death was 23 months. Three deaths (6%) occurred within 12 months of ICD implantation. Appropriate therapy (ATP or shock) occurred in 19 (38%). Inappropriate therapy occurred in 6 (12%).Rates of appropriate shocks and inappropriate therapy (shocks and ATP) and significant valvular incompetence were higher amongst deceased patients (P=0.03 OR 5.9 95% CI 1.3-27) and (P=0.02 OR 12 95% CI 1.3-112). Univariate analysis identified diuretic use (P=0.008 95% C.I. 0.05 to 0.63) and appropriate shock (P= 0.025 95% C.I. 1.25 to 26.3) as predictors of mortality.ConclusionOctogenarians make up a small but increasing number of ICD recipients. This study highlights high survival rates at one year with acceptable rates of appropriate and inappropriate device therapy. Ongoing debate regarding the appropriateness of ICD in very elderly patients is warranted.Key words: sudden cardiac death, implantable defibrillators, octogenarians 相似文献
88.
Bahareh Honarparvar Sachin A Pawar Cláudio Nahum Alves Jer?nimo Lameira Glenn EM Maguire José Rogério A Silva Thavendran Govender Hendrik G Kruger 《Journal of biomedical science》2015,22(1)
Background
Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC50 values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC50) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.Results
The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC50 = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC50 = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆Gsolv) were also considered.Conclusions
A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC50 data.Electronic supplementary material
The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users. 相似文献89.
90.
Subacute calorie restriction and rapamycin discordantly alter mouse liver proteome homeostasis and reverse aging effects 下载免费PDF全文
Dao‐Fu Dai Ying A. Chiao Ellen K. Quarles Edward J. Hsieh David Crispin Jason H. Bielas Nolan G. Ericson Richard P. Beyer Vivian L. MacKay Michael J. MacCoss Peter S. Rabinovitch 《Aging cell》2015,14(4):547-557
Calorie restriction (CR) and rapamycin (RP) extend lifespan and improve health across model organisms. Both treatments inhibit mammalian target of rapamycin (mTOR) signaling, a conserved longevity pathway and a key regulator of protein homeostasis, yet their effects on proteome homeostasis are relatively unknown. To comprehensively study the effects of aging, CR, and RP on protein homeostasis, we performed the first simultaneous measurement of mRNA translation, protein turnover, and abundance in livers of young (3 month) and old (25 month) mice subjected to 10‐week RP or 40% CR. Protein abundance and turnover were measured in vivo using 2H3–leucine heavy isotope labeling followed by LC‐MS/MS, and translation was assessed by polysome profiling. We observed 35–60% increased protein half‐lives after CR and 15% increased half‐lives after RP compared to age‐matched controls. Surprisingly, the effects of RP and CR on protein turnover and abundance differed greatly between canonical pathways, with opposite effects in mitochondrial (mt) dysfunction and eIF2 signaling pathways. CR most closely recapitulated the young phenotype in the top pathways. Polysome profiles indicated that CR reduced polysome loading while RP increased polysome loading in young and old mice, suggesting distinct mechanisms of reduced protein synthesis. CR and RP both attenuated protein oxidative damage. Our findings collectively suggest that CR and RP extend lifespan in part through the reduction of protein synthetic burden and damage and a concomitant increase in protein quality. However, these results challenge the notion that RP is a faithful CR mimetic and highlight mechanistic differences between the two interventions. 相似文献