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41.
Philippe M. Loiseau Kaluvu Balaraman Gillian Barratt Sbastien Pomel Rmy Durand Frdric Frzard Bruno Figadre 《Molecules (Basel, Switzerland)》2022,27(7)
There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the development of the series from the first isolated natural compounds through several hundred synthetized molecules to an optimized compound exhibiting an in vitro IC50 value of 0.2 µM against Leishmania donovani, and a selectivity index value of 187, together with in vivo activity on the L. donovani/hamster model. Attempts to establish structure–activity relationships are described, as well as studies that have attempted to determine the mechanism of action. For the latter, it appears that molecules of this series act on multiple targets, possibly including the immune system, which could explain the observed lack of drug resistance after in vitro drug pressure. We also show how nanotechnology strategies could valorize these drugs through adapted formulations and how a mechanistic targeting approach could generate new compounds with increased activity. 相似文献
42.
《Wave Motion》2020
Acoustoelastic effect describes the change of ultrasound velocity due to the initial stress. Its simulation involves a numerical analysis of nonlinear elastodynamics and requires high accuracy in the time domain. A time–space finite element formulation, derived from the quadratic interpolation of the acceleration within a time segment, is proposed for an accurate simulation of the acoustoelastic effect in the present study. Ten different integration schemes are generated based on this formulation and nine of them are found to be conditionally stable. Among the nine stable schemes, one is found to obtain a spectral radius of one when the normalized step ratio is less than 5.477, indicating no numerical dissipation or numerical divergence. Compared with integration schemes from previous studies, this integration scheme demonstrates better performance in calculation accuracy and energy conservation. A two-stage approach, namely the static stage and the dynamic stage, has been employed in the simulation of the acoustoelastic effect. The former stage is adopted to obtain the initial stress and the latter stage, where the proposed integration scheme is implemented, is adopted to simulate the ultrasound propagation in an initial stress state. The simulation results of the dynamic stage show that the ultrasound velocity increases in a compression stress state and decreases in a tension stress state for aluminum alloy, which is in good agreement with previous experimental studies. Together with the simulation result of the static stage, it is conjectured that the acoustoelastic effect results from the stress-dependent elastic modulus. 相似文献
43.
Impacts of localized enzymolysis and sonication on physical, techno-functional, and structure attributes of sunflower meal protein (SMP) and its hydrolysate (SMPH) were studied. SMP was subjected to enzymolysis (using alcalase) to prepare SMPH with various degrees of hydrolysis (6–24% DH). Enzymolysis decreased colour lightness, turbidity, and particle size of unsonicated and sonicated SMP, while it increased the absolute values of zeta potential (P < 0.05). Sonication improved oil absorption capacity and dispersibility over unsonicated samples. Contrarily, sonicated preparations showed a decrease in water holding capacity. Intrinsic fluorescence and FTIR spectral analyses suggested that SMPH had more movable/flexible secondary structures than SMP. Moreover, the changes in sulfhydryl clusters and disulfide linkages following sonication demonstrated limited unfolding of SMP and SMPH structure and decrease in intermolecular interactions. SDS-PAGE profile exhibited significant reduction in molecular weight (MW) of sonicated SMP, whereas did not display differences between unsonicated and sonicated SMPH. From further MW analysis, SMPH was categorized with high proportion of small-sized peptides ≤ 3 kDa fractions, which increased from 78.64 to 93.01% (control) and from 82.3 to 93.88% (sonication) with enzymolysis (6–24DH). Localized enzymolysis and sonication can be utilised to modify the physical and conformational attributes of SMP and SMPH, which could enhance their functionalities and broaden the utilisation area in food industry. 相似文献
44.
针对柱状装药的周向预制破片战斗部,结合无量纲分析方法和爆炸驱动理论,确定了影响破片和冲击波相遇位置的关键参数,给出了由缩比战斗部推广预测原型战斗部爆炸产生的破片冲击波作用时序的方法。采用ANSYS/LS-DYNA有限元软件进行数值模拟,对比验证了理论分析和数值试验结果,分析了战斗部缩比比例对冲击波和破片作用时序的影响。结果表明:缩比模型与原型战斗部爆炸产生的破片和冲击波的相遇位置之比和相遇时间之比主要取决于两模型的质量比,在不考虑破片速度衰减时,两模型中载荷相遇位置之比和相遇时间之比等于其质量比的0.33次方。受破片速度衰减影响,该方法仅适用于质量缩比不小于0.2的模型。 相似文献
45.
46.
Isabel V. L. Wilkinson Kelly J. Perkins Hannah Dugdale Lee Moir Aini Vuorinen Maria Chatzopoulou Sarah E. Squire Sebastian Monecke Alexander Lomow Marcus Geese Philip D. Charles Peter Burch Jonathan M. Tinsley Graham M. Wynne Stephen G. Davies Francis X. Wilson Fraydoon Rastinejad Shabaz Mohammed Kay E. Davies Angela J. Russell 《Angewandte Chemie (International ed. in English)》2020,59(6):2420-2428
Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies. 相似文献
47.
A. M. Polyakov 《Journal of Geometry and Physics》1988,5(4):595-600
We analyze three-dimensional gauge theory with Chern-Simons action, which arises in the context of high Tc superconductivity. We show that the main effect in this theory is the change of spin and statistics of charged particles. Also, the amplitudes of particle propagation acquire phases dependent on the topology of the knot formed by their trajectories. In the end, we discuss possible generalizations of this theory, and their relations to strings. 相似文献
48.
数学建模活动对培养人才的作用 总被引:25,自引:0,他引:25
宿维军 《数学的实践与认识》2002,32(5):867-868
文章论述建模活动对培养人才的作用 ,对专科院校高等数学教学改革具有启发性 . 相似文献
49.
C. Connell McCluskey 《Journal of Mathematical Analysis and Applications》2008,338(1):518-535
A very general compartmental model of the spread of an infectious disease with mass action incidence is given. The global stability of this system is completely determined using Lyapunov functions. The general system exhibits the traditional threshold behaviour. The dimension of the system is arbitrary, allowing, in particular, for detailed modelling of the distribution of latency times for tuberculosis. 相似文献
50.
The fluorescence quenching of Rhodamine 6G (R6G) by graphene oxide (GO) was interrogated by R6G fluorescence measurements using a set of controlled GO samples with varied C/O ratios as the quencher.The carbonyl groups on the GO nanosheet turned to play a dominant role in quenching the R6G fluorescence.The quenching in the static regime can be described by the "sphere of action" model.The significant absorption of the R6G fluorescence by the ground-state complex formed between R6G and GO was identified to be responsible for the static quenching.This work offers helpful insights into the fluorescence quenching mechanisms in the R6G/GO system. 相似文献