Search results for "ship"

Public Administration and the Study of Political Order: Towards a Framework for Analysis

2020

The contribution of this study is two-fold: First, it outlines a conceptual framework on political order; and secondly, it offers empirical illustrations on the case of Nordic cooperation. Taken together, the article makes a plea for public administration scholarship in the study of political order. Political order consists of a relatively stable arrangement of institutions that are fairly formalized and institutionalized. A common political order, moreover, entails that relevant institutions: (i) are fairly independent of pre-existing institutions; (ii) are relatively integrated and internally cohesive; and (iii) are reasonably able to influence governance processes within other institutio…

The American nuclear family in the TV series "The Simpsons"

1999

Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides

2012

Irreversible epidermal growth factor receptor (EGFR) inhibitors contain a reactive warhead which covalently interacts with a conserved cysteine residue in the kinase domain. The acrylamide fragment, a commonly employed warhead, effectively alkylates Cys797 of EGFR, but its reactivity can cause rapid metabolic deactivation or nonspecific reactions with off-targets. We describe here a new series of irreversible inhibitors containing a 3-aminopropanamide linked in position 6 to 4-anilinoquinazoline or 4-anilinoquinoline-3- carbonitrile driving portions. Some of these compounds proved to be as efficient as their acrylamide analogues in inhibiting EGFR-TK (TK = tyrosine kinase) autophosphorylati…

Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening

2013

The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.

Effects of amsacrine (m-AMSA), a new aminoacridine antitumor drug, on the rabbit heart.

1983

There is emerging clinical evidence that amsacrine (m-AMSA) administration may be associated with cardiotoxic effects such as severe, even fatal, ventricular arrhythmias and impairment of the inotropic performance of the heart. Information on the cardiac effects of m-AMSA in animals is scanty. Studies on mice, dogs, and monkeys have not evidenced the cardiotoxicity of the compound. The data presented in this paper show that m-AMSA causes acute ECG alterations in normal rabbits and a dose-related negative inotropic effect on the isolated rabbit heart, suggesting that this species may be a useful model for the study of the cardiac actions of this antiblastic.

Time trials versus time-to-exhaustion tests: Effects on critical power, W0, and oxygen-uptake kinetics

2018

Purpose: To investigate single-day time-to-exhaustion (TTE) and time-trial (TT) -based laboratory tests values of critical power (CP), W prime (W0), and respective oxygen-uptake-kinetic responses. Methods: Twelve cyclists performed a maximal ramp test followed by 3 TTE and 3 TT efforts interspersed by 60 min recovery between efforts. Oxygen uptake (VO 2) was measured during all trials. The mean response time was calculated as a description of the overall VO 2-kinetic response from the onset to 2 min of exercise. Results: TTE-determined CP was 279 ± 52 W, and TT-determined CP was 276 ± 50 W (P = .237). Values of W0 were 14.3 ± 3.4 kJ (TTE W0) and 16.5 ± 4.2 kJ (TT W0) (P = .028). While a hig…

Topological Approach to Analgesia

1994

Alla ricerca dei fattori rilevanti nell’adozione dei sistemi di gestione della performance nelle amministrazioni pubbliche territoriali. L’analisi di…

2013

La ricerca scientifica ha dimostrato che la gestione della performance nelle amministrazioni pubbliche sta oggi spostando il proprio focus dalla mera attività di raccolta e rendicontazione di dati alla generazione di informazioni atte a supportare la formulazione di decisioni. L’analisi comparativa dei casi di studio analizzati in questo articolo mira ad identificare i fattori critici sottostanti alla progettazione e all’utilizzo dei sistemi di gestione della performance nelle amministrazioni regionali. Da questa analisi emerge che alcune variabili risultano essenziali ai fini di un’efficace adozione dei sistemi di performance management. Tra queste variabili sono annoverabili: il ruolo del…

Semi-physiologic model validation and bioequivalence trials simulation to select the best analyte for acetylsalicylic acid

2015

Abstract The objective of this paper is to apply a previously developed semi-physiologic pharmacokinetic model implemented in NONMEM to simulate bioequivalence trials (BE) of acetyl salicylic acid (ASA) in order to validate the model performance against ASA human experimental data. ASA is a drug with first-pass hepatic and intestinal metabolism following Michaelis–Menten kinetics that leads to the formation of two main metabolites in two generations (first and second generation metabolites). The first aim was to adapt the semi-physiological model for ASA in NOMMEN using ASA pharmacokinetic parameters from literature, showing its sequential metabolism. The second aim was to validate this mod…

Application of C1-Esterase Inhibitor During Reperfusion of Ischemic Myocardium

2001

Background—Complement activation during reperfusion of ischemic myocardium augments myocardial injury, and complement inhibition with C1-esterase inhibitor (C1-INH) at the time of reperfusion exerts marked cardioprotective effects in experimental studies. Application of C1-INH in newborns, however, was recently reported to have dangerous and even lethal side effects. This study addresses the essential role of dosage in studies using C1-INH.Methods and Results—Cardioprotection by C1-INH was examined in a pig model with 60 minutes of coronary occlusion followed by 120 minutes of reperfusion. C1-INH was administered intravenously 5 to 10 minutes before coronary reperfusion without heparin at a…