RESUMO
We present a fast-simulation application based on a deep neural network, designed to create large analysis-specific datasets. Taking as an example the generation of W + jet events produced in s = 13 TeV proton-proton collisions, we train a neural network to model detector resolution effects as a transfer function acting on an analysis-specific set of relevant features, computed at generation level, i.e., in absence of detector effects. Based on this model, we propose a novel fast-simulation workflow that starts from a large amount of generator-level events to deliver large analysis-specific samples. The adoption of this approach would result in about an order-of-magnitude reduction in computing and storage requirements for the collision simulation workflow. This strategy could help the high energy physics community to face the computing challenges of the future High-Luminosity LHC.
Assuntos
AMP Cíclico , Transporte Biológico , Biofarmácia , Permeabilidade da Membrana Celular , Química Farmacêutica , AMP Cíclico/metabolismo , AMP Cíclico/farmacologia , Enzimas/metabolismo , Hormônios/metabolismo , Humanos , Metabolismo dos Lipídeos , Metabolismo/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacosAssuntos
Butilaminas/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Etanol/farmacologia , Naftalenos/farmacologia , Respiração/efeitos dos fármacos , Simpatolíticos/farmacologia , Anestésicos Locais/farmacologia , Animais , Cães , Feminino , Masculino , Camundongos , Coelhos , Simpatomiméticos/farmacologiaRESUMO
The therapeutic usefulness of intravenously infused dopamine in congestive heart failure and in shock prompted us to synthesize a wide series of 3,4-O-diesters of dopamine and N-substituted derivatives to obtain an orally active dopamine-like prodrug having adequate absorption and duration of action. The pharmacological results and in particular, the hemodynamic studies in the dog led to the selection of ibopamine, i.e. the 3,4-diisobutyryl ester of N-methyldopamine and to its development as a useful drug for the chronic treatment of congestive heart failure. The choice of ibopamine from among several analogs was also influenced by other favourable properties such as good chemical stability in pharmaceutical formulations and in the biopharmaceutical phases of the absorption, and fast enzymatic activation of the prodrug by plasma and peripheral tissue esterases; the latter property appeared desirable to avoid any accumulation in the central nervous system and consequent undesired side effects. The isomeric mixture of 3-O- and 4-O-isobutyrates of N-methyldopamine as well as the main conjugated metabolites, i.e. the 3-O- and 4-O-sulphate and 4-O-beta-glucuronide of N-methyldopamine were synthesized as analytical references in metabolic studies and for the investigation on their pharmacokinetic and pharmacological properties. Dopamine O-sulphates were also prepared using the methods developed for the corresponding N-methyl derivatives.