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It is urgent to develop new antimalarial drugs with good therapeutic effects to address the emergence of drug resistance. Here, the artelinic acid-choline derivative (AD) was synthesized by dehydration reaction and esterification reaction, aimed to avoid the emergence of drug resistance by synergistic effect of artemisinins and choline derivative, which could compete with choline for rate-limiting enzymes in the phosphatidylcholine (PC) biosynthetic pathway. AD was formulated into liposomes (ADLs) by the thin-film hydration method. Efficacy of ADLs was evaluated by Peters 4-day suppression test. The suppression percentage against Plasmodium yoelii BY265 (PyBY265) in ADLs group was higher than those of positive control groups (dihydroartemisinin liposomes, P < 0.05) and other control groups (P ⩽ 0.05) at the doses of 4.4, 8.8, 17.6 µmol (kg·d)−1, respectively. The negative conversion fraction, recrudescence fraction and survival fraction of ADLs group were superior to other control groups. Pharmacokinetics in rats after intravenous injection suggested that ADLs exhibited higher exposure levels (indexed by area under concentration-time curve) than that of AD solution, artelinic acid liposomes or artelinic acid solution (P < 0.01). Taken together, ADLs exhibited promising antimalarial efficacy and pharmacokinetic characteristics.
We prove the genus-one restriction of the all-genus Landau–Ginzburg/Calabi–Yau conjecture of Chiodo and Ruan, stated in terms of the geometric quantization of an explicit symplectomorphism determined by genus-zero invariants. This gives the first evidence supporting the higher-genus Landau–Ginzburg/Calabi–Yau correspondence for the quintic
-fold, and exhibits the first instance of the ‘genus zero controls higher genus’ principle, in the sense of Givental’s quantization formalism, for non-semisimple cohomological field theories.
The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.
The Beidou System (BDS) started functioning at the end of 2012. The Yaw-Steering (YS) attitude mode for Inclined Geosynchronous Orbit (IGSO) and Medium Earth Orbit (MEO) satellites in BDS ensures that the solar panels face the Sun. The orbit radial accuracies for IGSO/MEO satellites are 0·5 m and the User Equivalent Range Errors (UERE) are 1·5 m in YS mode. BDS-2 satellites adopt Orbit-Normal (ON) mode to meet the power supply and thermal control requirements of the satellite during deep Earth eclipse periods. In ON mode, long-term orbit ephemeris accuracy monitoring in the Operational Control System (OCS) of BDS indicates that the orbit accuracies for IGSO/MEOs are reduced to a few hundreds of metres, seriously affecting the positioning accuracy and navigation service capability of the BDS system. Solar Radiation Pressure (SRP) is difficult to model in ON mode. Continuous Yaw-Steering (CYS) mode is available for new generation Beidou satellites launched since 2015. The orbit accuracies for these new generation Beidou (BDS-3) satellites were estimated based on BDS monitoring station data and SRP models including ECOM 9/5/3. The evaluation method consisted of four steps, namely, orbit internal consistency analysis, UERE calculation, Satellite Laser Ranging (SLR) data fitting Root Mean Square (RMS) determinations and positioning performance analysis; the data gathering period lasted for more than 60 days and included two CYS periods and one ON period. The experiments showed that the orbit accuracy of the radial component in CYS mode for the BDS-3 satellites degrades by 2 to 3 cm and positioning accuracy degrades only by 1 cm over that in YS mode which is just a small reduction in accuracy compared with the decimetre-level BDS orbit accuracy and the metre-level single point positioning accuracy with BDS pseudorange data. This overcomes declining orbit and positioning accuracy issues in ON mode for BDS-2 satellites. Other results also show that the reliability of BDS has been improved.
SCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.
Genomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.
Results and conclusions
A novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.
The Chinese Solar and Geophysical Data (CSGD) was first issued at the Beijing Astronomical Observatory, Chinese Academy of Sciences (now the headquarter of the National Astronomical Observatories, Chinese Academy of Sciences) in 1971, when China’s satellite-industry was booming. CSGD covers the observational data (observations of the sunspots, solar flares, solar radio bursts, ionospheric storm and geomagnetic storm) from a couple of domestic observatories and the forecast data. The compiler of CSGD still keeps the data exchange with other institutes worldwide. The type of the dataset includes texts, tables, figures and so on. Up to now, we have electronized all the historic archives, making them easily accessible to people who are interested in them.
Gamma prime (γ′) stability and its influence on tensile behavior of a newly developed wrought superalloy with various Fe contents was studied both experimentally and thermodynamically. The results show that the γ′-solvus temperature is higher and γ–γ′ lattice mismatch is bigger in the alloy with the lower Fe content. During long-term thermal exposure at 650–750 °C, the coarsening behavior of γ′ precipitates follows Ostwald ripening kinetics and the lower Fe content can decrease the coarsening rate of γ′ precipitates due to the increase of the activation energy for γ′ coarsening. Moreover, the lower Fe content can retard the transformation from γ′ to η phase. The tensile properties of the alloys with different Fe contents are almost same after standard heat treatment. However, after thermal exposure, the decrease of tensile strength in the alloy with lower Fe content is less than that of the alloys with higher Fe content due to the improvement of γ′ stability.
We address a queueing control problem considering service times and conversion times
following normal distributions. We formulate the multi-server queueing control problem by
constructing a semi-Markov decision process (SMDP) model. The mechanism of state
transitions is developed through mathematical derivation of the transition probabilities
and transition times. We also study the property of the queueing control system and show
that optimizing the objective function of the addressed queueing control problem is
equivalent to maximizing the time-average reward.
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