Novel and potent inhibitors of Plasmodium falciparum plasmepsin II were identified by post‐processing the results of a docking screening with BEAR, a recently reported procedure for the refinement and rescoring of docked ligands in virtual screening. FRET substrate degradation assays performed on the 30 most promising compounds resulted in 26 inhibitors with IC50 values ranging from 4.3 nM to 1.8 μM .
Through this paper, we call for a distributed, Internet-based collaboration to address one of the worst plagues of our present world, malaria. The spirit is a nonproprietary peer-production of information-embedding goods. And we propose to use the grid technology to enable such a worldwide "open-source" like collaboration. The first step toward this vision has been achieved during the summer 2005 on the enabling grids for E-scienceE (EGEE) grid infrastructure where 42 million ligands were docked for a total amount of 80 CPU years in 6 weeks in the quest for new drugs. The impact of this first deployment has significantly raised the interest of the research community so that several laboratories all around the world expressed interest to propose targets for a second large-scale deployment against malaria. 相似文献
Malolactic fermentation (MLF), which is conducted by lactic acid bacteria (LAB), has a significant influence on the stability and organoleptic quality of wine. Recent studies have shown that when MLF is carried out in oak wood barrels, LAB were also able to interact with wood and increase volatile compound contents such as vanillin during MLF. The release of these compounds indicates that LAB may convert vanillin precursors present in oak wood. In this work, the effect of commercial glycosidases on the released vanillin was firstly studied. This aldehyde is present in wood extracts in monoglycosidic forms where the major glycones are arabinose and xylose. Other aglycons released during MLF in barrels, syringaldehyde and whisky-lactones, can be considered as other sources of aroma. Secondly, strains selected with high activities toward glycoside substrates could hydrolyse vanillin glycoside precursors from oak wood with the same efficiency as commercial enzymes. 相似文献
Brittleness, relative high friction coefficient and wear rate limit the applications of ceramic coatings as wear-resistant layers. However, because embedding additives with ceramic matrix has demonstrated to be an effective way to improve coating performances, different contents and size of h-BN were added into an YSZ suspension. Afterwards, the YSZ/h-BN composite coatings were manufactured by suspension plasma spray and their tribological analysis indicated that: i) the reduction of the friction coefficient and wear rate can be achieved by incorporating h-BN into YSZ coating. ii) finer h-BN particle is more helpful to enhance the tribological properties of the coating. iii) the optimum content is dependent on h-BN particle sizes. iv) when the contents and the size of the h-BN inclusion increase, the probability distribution of the micro-hardness can become bi-modal. Three worn surface conditions were summarized and their wear mechanisms were discussed as well. 相似文献
In an attempt to maintain the elimination of COVID-19 in New Zealand, all international arrivals are required to spend 14 days in government-managed quarantine and to return a negative test result before being released. We model the testing, isolation and transmission of COVID-19 within quarantine facilities to estimate the risk of community outbreaks being seeded at the border. We use a simple branching process model for COVID-19 transmission that includes a time-dependent probability of a false-negative test result. We show that the combination of 14-day quarantine with two tests is highly effective in preventing an infectious case entering the community, provided there is no transmission within quarantine facilities. Shorter quarantine periods, or reliance on testing only with no quarantine, substantially increases the risk of an infectious case being released. We calculate the fraction of cases detected in the second week of their two-week stay and show that this may be a useful indicator of the likelihood of transmission occurring within quarantine facilities. Frontline staff working at the border risk exposure to infected individuals and this has the potential to lead to a community outbreak. We use the model to test surveillance strategies and evaluate the likely size of the outbreak at the time it is first detected. We conclude with some recommendations for managing the risk of potential future outbreaks originating from the border. 相似文献
A series of six oleoglycerides: 1,2-diaceto-3-olein, 1,2-dibutyro-3-olein, 1-aceto-3-olein, 1-butyro-3-olein, 1,3-diolein, and 1-mono-olein, was prepared and purified, and some of their physical properties were determined.
Data on densities and refractive indices of the compounds revealed that substitution of short-chain acyl groups for one or both of the hydroxyl groups in 1-mono-olein increases the density and decreases the refractive index. The effect is more pronounced for the aceto than the butyro groups.
By the capillary tube method, melting- and transition-point data were determined for each glyceride. For the triglycerides, 1,2-diaceto-3-olein and 1,2-dibutyro-3-olein, one melting point and two transition points for each were found. For the diglycerides, 1-aceto-3-olein and 1-butyro-3-olein, two melting points and two transition points for each were found. Two melting points and one transition point each for 1,3-diolein and 1-mono-olein were found. These melting and transition points were substantiated by heating-curve data.
Where possible, dilatometric measurements were made for the various polymorphic forms of the glycerides. From the data were calculated expansibilities in the solid and liquid states, melting dilations or volume changes accompanying transformations, and dilatometric melting points.