基于生存模型的沥青路面预防性养护经济性评价

为探索经济、有效的沥青路面养护方法,降低沥青路面的养护费用,对沥青路面的预防性养护进行了全寿命经济性评价．首先根据美国加利福尼亚州交通部门的路面观测数据,采用生存模型建立了沥青路面在裂缝类预防性养护情况下的全寿命周期的性能模型; 进而,通过概率分析建立了路面的性能－成本模型,分析了不同破坏准则下预防性养护措施的经济性,并与矫正性修复措施的经济性进行了对比．结果表明,在沥青路面的寿命周期内,一直采用预防性养护的成本较采用矫正性修复的成本平均节约了27%,采用每两次矫正性修复间加入两次预防性养护的成本较一直使用矫正性修复的成本平均节约了17%． 分析结果还表明,越早进行预防性养护,沥青路面的寿命周期成本越低．     

A gravitationally lensed quasar with quadruple images separated by 14.62 arcseconds

Gravitational lensing is a powerful tool for the study of the distribution of dark matter in the Universe. The cold-dark-matter model of the formation of large-scale structures (that is, clusters of galaxies and even larger assemblies) predicts the existence of quasars gravitationally lensed by concentrations of dark matter so massive that the quasar images would be split by over 7 arcsec. Numerous searches for large-separation lensed quasars have, however, been unsuccessful. All of the roughly 70 lensed quasars known, including the first lensed quasar discovered, have smaller separations that can be explained in terms of galaxy-scale concentrations of baryonic matter. Although gravitationally lensed galaxies with large separations are known, quasars are more useful cosmological probes because of the simplicity of the resulting lens systems. Here we report the discovery of a lensed quasar, SDSS J1004 + 4112, which has a maximum separation between the components of 14.62 arcsec. Such a large separation means that the lensing object must be dominated by dark matter. Our results are fully consistent with theoretical expectations based on the cold-dark-matter model.     

FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence.     

应用小波的PV振荡周期多分辨率检测

该文提出了一种新的使用小波技术检测PV数据信号振荡周期的方法. 首先使用小波技术对PV数据进行降噪;然后在不同分辨率上,应用冗余二进制离散小波变换(DDWT)来分解PV振荡信号,并检测该信号的小波系数极值,重构PV信号,避免降噪后的PV信号失真;最后基于本文提出的新算法,计算获得PV振荡信号的周期.     

Three modes of synaptic vesicular recycling revealed by single-vesicle imaging

Synapses recycle their spent vesicles in order to keep up with on-going neurotransmitter release. To investigate vesicle recycling in the small synapses of hippocampal neurons, we have used an optical recording method that permits us to resolve single-vesicle events. Here we show that an exocytic event can terminate with three modes of vesicle retrieval: a fast (400-860 ms) 'kiss-and-run' mode that has a selective fusion pore; a slow (8-21 s) 'compensatory' mode; and a 'stranded' mode of recycling, in which a vesicle is left on the cell surface until a nerve impulse triggers its retrieval. We have also observed that, in response to a nerve impulse, synapses with low release probability primarily use the kiss-and-run mode, whereas high release probability terminals predominantly use the compensatory mode of vesicle retrieval.     

Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis

The ability to cross host barriers is an essential virulence determinant of invasive microbial pathogens. Listeria monocytogenes is a model microorganism that crosses human intestinal and placental barriers, and causes severe maternofetal infections by an unknown mechanism. Several studies have helped to characterize the bacterial invasion proteins InlA and InlB. However, their respective species specificity has complicated investigations on their in vivo role. Here we describe two novel and complementary animal models for human listeriosis: the gerbil, a natural host for L. monocytogenes, and a knock-in mouse line ubiquitously expressing humanized E-cadherin. Using these two models, we uncover the essential and interdependent roles of InlA and InlB in fetoplacental listeriosis, and thereby decipher the molecular mechanism underlying the ability of a microbe to target and cross the placental barrier.