Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.
In the photoreaction of Escherichia coli IM303 (superoxide dismutase (SOD)-de®cient mutant) and MM294 (wild-type strain) with TiO 2 particles, the viability of strain IM303 decreased linearly with photoreaction time, while the time pro®le of the viability of strain MM294 exhibited a curved form. Using strain MM294 with varied initial SOD activities, the TiO 2 photoreaction tests were conducted at incident light intensities of I 0 = 4,8 and 14 W m
À2, and the time pro®les of bacterial viabilities were analyzed on the basis of the series-event model. The value of n (corresponding to the step number in the series reaction kinetics described by the model) increased with an increase in initial SOD activity (A SOD,0 ), giving a mean value of A SOD,0 /n = 7.1 Â 10 À9 U cell À1 under the conditions examined. SOD activities in the cells of strain MM294 with A SOD,0 = 1.9 Â 10 À8 and 4.0 Â 10 À8 U cell
À1decreased with the progress of photoreaction conducted at I 0 = 14 W m
À2. The transition of intracellular SOD activities expressed was in agreement with the observed data by considering the changes in bacterial cell populations with varied SOD activities based on the proposed model.
A method involving atomic absorption spectrometry (AAS) with direct atomization has been developed for the determination of trace amounts of Cu and Pb in Si3N4 and S i c using a graphite furnace. The samples were ground to a particle size of less than 20 pm and mixed with 2.5 times the amount of graphite powder in a corundum mortar. A 0.5-3 mg amount of the mixed sample was weighed in a tared graphite cup and atomized in a cup-type graphite furnace. The absorbance was determined by integration of the spectral lines in the absorbance versus time spectrum. Calibration was effected using aqueous standard solutions. The absorbance versus time spectrum of Cu shows double peaks. On the basis of the X-ray diffraction patterns and scanning electron micrographs of the Si3N4-graphite powder mixture heated at the temperature of each atomization step, the first peak could be assigned to the Cu vaporizing from Si, and the second peak to the Cu vaporizing from Sic. The results for 12 a-Si3N4, two p-Si3N4 and two SIC samples were in good agreement with the values obtained by electrothermal AAS for liquid samples. The relative standard deviations for Cu (0.11-53.7 ppm d m ) and Pb (0.361.55 ppm m/m) are 1.639% (n = 5) and 4.3-17% (n = 5), respectively. The determination limits, corresponding to twice the standard deviation of the blank measurements, are 92 pg for Cu and 53 pg for Pb.
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