Robustness analysis of signaling transduction networks based on Monte-Carlo method

The dynamic behaviors of cell system were deep ly affected by structural complexity of cell signal transduction networks and uncertainty of kinetics parameters. How to quantitatively determinate the relation between system behaviors and parameters variations was an important p roblem of systems biology. In order to study robustness of NF - κB signal transduction networks, the parameters of system model were assigned to subject to stochastic distributions. Then, robustness of system output signal NF - κBn with respect to 64 parameters variations and amp litude variation of step input signal IKK was studied by means of Monte - Carlo method. The simulation results demonstrate that the oscillation behavior of system output signal NF - κBn is closely relative to 6 key rate constantswhose robustness isweak, and the amp litude variation of step input signal IKKmakes a great impact on the oscillation behavior of system output

A Genetic Algorithm for Locating the Multiscale Critical Slip Surface in Jointed Rock Mass Slopes

The joints have great influence on the strength of jointed rock mass and lead to the multiscale, nonhomogeneous, and anisotropic characteristics. In order to consider these effects, a new model based on a genetic algorithm is proposed for locating the critical slip surface (CSS) in jointed rock mass slope (JRMS) from its stress field. A finite element method (FEM) was employed to analyze the stress field. A method of calculating the mechanical persistence ratio (MPR) was used. The calculated multiscale and anisotropic characteristics of the MPR were used in the fitness function of genetic algorithm (GA) to calculate the factor of safety. The GA was used to solve optimization problems of JRMS stability. Some numerical examples were given. The results show that the multiscale and anisotropic characteristics of the MPR played an important role in locating the CSS in JRMS. The proposed model calculated the CSS and the factor of safety of the slope with satisfactory precision

Focused ultrasound-enhanced delivery of intranasally administered anti-programmed cell death-ligand 1 antibody to an intracranial murine glioma model

Immune checkpoint inhibitors have great potential for the treatment of gliomas; however, their therapeutic efficacy has been partially limited by their inability to efficiently cross the blood-brain barrier (BBB). The objective of this study was to evaluate the capability of focused-ultrasound-mediated intranasal brain drug delivery (FUSIN) in achieving the locally enhanced delivery of anti-programmed cell death-ligand 1 antibody (aPD-L1) to the brain. Both non-tumor mice and mice transcranially implanted with GL261 glioma cells at the brainstem were used in this study. aPD-L1 was labeled with a near-infrared fluorescence dye (IRDye 800CW) and administered to mice through the nasal route to the brain, followed by focused ultrasound sonication in the presence of systemically injected microbubbles. FUSIN enhanced the accumulation of aPD-L1 at the FUS-targeted brainstem by an average of 4.03- and 3.74-fold compared with intranasal (IN) administration alone in the non-tumor mice and glioma mice, respectively. Immunohistochemistry staining found that aPD-L1 was mainly located within the perivascular spaces after IN delivery, while FUSIN further enhanced the penetration depth and delivery efficiency of aPD-L1 to the brain parenchyma. The delivered aPD-L1 was found to be colocalized with the tumor cells after FUSIN delivery to the brainstem glioma. These findings suggest that FUSIN is a promising technique to enhance the delivery of immune checkpoint inhibitors to gliomas

Non-Markovian quantum interconnect formed by a surface plasmon polariton waveguide

Allowing the generation of effective interactions between distant quantum emitters (QEs) via flying photons, quantum interconnect (QI) is essentially a light-matter interface and acts as a building block in quantum technologies. A surface plasmon polariton (SPP) supported by a metallic waveguide provides an ideal interface to explore strong light-matter couplings and to realize QI. However, the loss of SPP in metal makes the mediated entanglement of the QEs damp with the increase of the distance and time, which hinders its applications. We propose a scheme of non-Markovian QI formed by the SPP of a metallic nanowire. A mechanism to make the generated entanglement of the QEs persistent is discovered. We find that, as long as bound states are formed in the energy spectrum of total QE-SPP system, the damping of the SPP-mediated entanglement is overcome even in the presence of the metal absorption to the SPP. Our finding enriches our understanding of light-matter couplings in absorptive medium and paves the way for using the SPP in designing QI.Comment: 7 pages and 3 figures in the main text. 3 pages in the supplemental materia

A simple and efficient method for isolating polymorphic microsatellites from cDNA

<p>Abstract</p> <p>Background</p> <p>Microsatellites in cDNA are useful as molecular markers because they represent transcribed genes and can be used as anchor markers for linkage and comparative mapping, as well as for studying genome evolution. Microsatellites in cDNA can be detected in existing ESTs by data mining. However, in most fish species, no ESTs are available or the number of ESTs is limited, although fishes represent half of the vertebrates on the earth. We developed a simple and efficient method for isolation of microsatellites from cDNA in fish.</p> <p>Results</p> <p>The method included normalization of 150 ng cDNA using 0.5 U duplex-specific nuclease (DSN) at 65°C for 30 min, enrichment of microsatellites using biotinylated oligonucleotides and magnetic field, and directional cloning of cDNA into a vector. We tested this method to enrich CA- and GA-microsatellites from cDNA of Asian seabass, and demonstrated that enrichment of microsatellites from normalized cDNA could increased the efficiency of microsatellite isolation over 30 times as compared to direct sequencing of clones from cDNA libraries. One hundred and thirty-nine (36.2%) out of 384 clones from normalized cDNA contained microsatellites. Unique microsatellite sequences accounted for 23.6% (91/384) of sequenced clones. Sixty microsatellites isolated from cDNA were characterized, and 41 were polymorphic. The average allele number of the 41 microsatellites was 4.85 ± 0.54, while the expected heterozygosity was 0.56 ± 0.03. All the isolated microsatellites inherited in a Mendelian pattern.</p> <p>Conclusion</p> <p>Normalization of cDNA substantially increased the efficiency of enrichment of microsatellites from cDNA. The described method for isolation of microsatellites from cDNA has the potential to be applied to a wide range of fish species. The microsatellites isolated from cDNA could be useful for linkage and comparative mapping, as well as for studying genome evolution.</p

上海嘉定区35岁以上首诊测压工作的回顾与展望

Objective: To understand the policy development of blood pressure test blood pressure test among residents above 35 years old at first visit in Jiading district in Shanghai in order to provide a better reference for the development of the blood pressure test. Methods: Retrospect is from the following three aspects: the policy advancement of the blood pressure measurement, the progress of the work and the next step of the development of blood pressure test to first diagnosis above 35 years old. Results: The total of policy documents related to prevention and treatment of chronic disease, published by national, Shanghai municipal and Jiading District government department are 185. There are 22 policy documents aspects of the prevention and control of hypertension among these documents, and 11 involving measurement of blood pressure test in the first diagnosis patients above 35 years old, 5.95% proportion of above total policy documents. These policy documents involving blood pressure test are technical solutions. There are 3 policy documents (1 Shanghai municipal, 2 Jiading District) involving measurement of blood pressure test published in 1999 and before; and 4 policy documents (2 national, 2 Shanghai municipal) during 2000-2008; and 4 policy documents (4 national) published after 2009. At present, the work runs well in Jiading district, and the work runs better in the community health service center than the comprehensive hospital. Conclusions: More and more documents were released from the national department, provincial department and local health department so that solid policy guarantees the work of blood pressure test for residents above 35 years old at first visit in Jiading district in Shanghai. The development and use of information software provides a powerful tool for the pressure measurement. Along with the perfect of supporting measures, the work of blood pressure test to first diagnosis above 35 years old will be further developed and improved.目的  了解上海嘉定区35岁以上首诊测压工作的发展历程，为更好地推进首诊测压工作提供参考。方法  按照政策出台时间、类别和内容，围绕国家、上海市和嘉定区三份层面，从测压政策的演变、测压工作的进展和下一步的发展三份方面对上海嘉定区35岁以上首诊测压工作的进展和走向进行了回顾与展望。结果  国家、上海市、嘉定区出台的相关慢性病政策文件共185份，其中高血压防控方面的有22份，涉及到首诊测压政策方面的有11份，占慢病政策的5.95%。在出台的首诊测压政策文件中，均为技术性的文件。1999年及以前的政策有3份（其中上海市1份、嘉定区2份）；2000～2008年期间的政策共有4份（其中国家2份、上海市2份）；2009年及以后的政策有4份（均为国家的）。目前全区的测压工作进展良好，社区卫生服务中心的测压工作相对比二级医院的发展得好。结论  国家、省市和县区级卫生部门的政策性文件的陆续出台，为35岁以上首诊测压工作提供坚实的政策性保障，信息软件的开发与使用为测压工作提供了有力的手段。 随着测压工作的各项配套措施推进，35岁以上首诊测压工作会进一步得到发展与提高

Dexmedetomidine post-treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF-1α signalling.

Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in the apoptotic process during cardiac ischaemia/reperfusion (I/R) injury. This study aimed to investigate whether post-treatment with dexmedetomidine (DEX) could protect against I/R-induced cardiac apoptosis in vivo and in vitro via regulating HIF-1α signalling pathway. Rat myocardial I/R was induced by occluding the left anterior descending artery for 30 minutes followed by 6-hours reperfusion, and cardiomyocyte hypoxia/reoxygenation (H/R) was induced by oxygen-glucose deprivation for 6 hours followed by 3-hours reoxygenation. Dexmedetomidine administration at the beginning of reperfusion or reoxygenation attenuated I/R-induced myocardial injury or H/R-induced cell death, alleviated mitochondrial dysfunction, reduced the number of apoptotic cardiomyocytes, inhibited the activation of HIF-1α and modulated the expressions of apoptosis-related proteins including BCL-2, BAX, BNIP3, cleaved caspase-3 and cleaved PARP. Conversely, the HIF-1α prolyl hydroxylase-2 inhibitor IOX2 partly blocked DEX-mediated cardioprotection both in vivo and in vitro. Mechanistically, DEX down-regulated HIF-1α expression at the post-transcriptional level and inhibited the transcriptional activation of the target gene BNIP3. Post-treatment with DEX protects against cardiac I/R injury in vivo and H/R injury in vitro. These effects are, at least in part, mediated via the inhibition of cell apoptosis by targeting HIF-1α signalling