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1.
Science ; 380(6649): eabh1322, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37167351

RESUMO

The gravitationally lensed supernova Refsdal appeared in multiple images produced through gravitational lensing by a massive foreground galaxy cluster. After the supernova appeared in 2014, lens models of the galaxy cluster predicted that an additional image of the supernova would appear in 2015, which was subsequently observed. We use the time delays between the images to perform a blinded measurement of the expansion rate of the Universe, quantified by the Hubble constant (H0). Using eight cluster lens models, we infer [Formula: see text]. Using the two models most consistent with the observations, we find [Formula: see text]. The observations are best reproduced by models that assign dark-matter halos to individual galaxies and the overall cluster.

2.
Science ; 347(6226): 1123-6, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25745167

RESUMO

In 1964, Refsdal hypothesized that a supernova whose light traversed multiple paths around a strong gravitational lens could be used to measure the rate of cosmic expansion. We report the discovery of such a system. In Hubble Space Telescope imaging, we have found four images of a single supernova forming an Einstein cross configuration around a redshift z = 0.54 elliptical galaxy in the MACS J1149.6+2223 cluster. The cluster's gravitational potential also creates multiple images of the z = 1.49 spiral supernova host galaxy, and a future appearance of the supernova elsewhere in the cluster field is expected. The magnifications and staggered arrivals of the supernova images probe the cosmic expansion rate, as well as the distribution of matter in the galaxy and cluster lenses.

3.
Clin Cancer Res ; 11(12): 4627-33, 2005 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15958649

RESUMO

PURPOSE: Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its consumption has been associated with decreased risk of certain types of cancers in humans. The oral bioavailability of the major green tea constituents, green tea catechins, is low, resulting in systemic catechin levels in humans many fold less than the effective concentrations determined in in vitro systems. We conducted this clinical study to test the hypothesis that the oral bioavailability of green tea catechins can be enhanced when consumed in the absence of food. EXPERIMENTAL DESIGNS: Thirty healthy volunteers were randomly assigned to one of the following doses of Polyphenon E (a decaffeinated and defined green tea catechin mixture): 400, 800, or 1,200 mg, based on the epigallocatechin gallate content (10 subjects per dose group). After an overnight fast, study participants took a single dose of Polyphenon E with or without a light breakfast, which consisted of one or two 4-oz muffins and a glass of water. Following a 1-week wash-out period, subjects were crossed over to take the same dose of Polyphenon E under the opposite fasting/fed condition. Tea catechin concentrations in plasma and urine samples collected after dosing were determined by high-pressure liquid chromatography analysis. RESULTS: Consistent with previous reports, epigallocatechin gallate and epicatechin gallate were present in plasma mostly as the free form, whereas epicatechin and epigallocatechin were mostly present as the glucuronide and sulfate conjugates. There was >3.5-fold increase in the average maximum plasma concentration of free epigallocatechin gallate when Polyphenon E was taken in the fasting condition than when taken with food. The dosing condition led to a similar change in plasma-free epigallocatechin and epicatechin gallate levels. Taking Polyphenon E in the fasting state did not have a significant effect on the plasma levels of total (free and conjugated) epigallocatechin, but resulted in lower plasma levels of total epicatechin. Urinary epigallocatechin gallate and epicatechin gallate levels were very low or undetectable following Polyphenon E administration with either dosing condition. Taking Polyphenon E under the fasting state resulted in a significant decrease in the urinary recovery of total epigallocatechin and epicatechin. Polyphenon E administered as a single dose over the dose range studied was generally well-tolerated by the study participants. Mild and transient nausea was noted in some of the study participants and was seen most often at the highest study agent dose (1,200 mg epigallocatechin gallate) and in the fasting condition. CONCLUSIONS: We conclude that greater oral bioavailability of free catechins can be achieved by taking the Polyphenon E capsules on an empty stomach after an overnight fast. Polyphenon E up to a dose that contains 800 mg epigallocatechin gallate is well-tolerated when taken under the fasting condition. This dosing condition is also expected to optimize the biological effects of tea catechins.


Assuntos
Catequina/análogos & derivados , Catequina/farmacocinética , Chá , Dor Abdominal/induzido quimicamente , Administração Oral , Adulto , Idoso , Área Sob a Curva , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/efeitos adversos , Catequina/sangue , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Flavonoides/sangue , Flavonoides/farmacocinética , Cefaleia/induzido quimicamente , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Náusea/induzido quimicamente
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