Impact of the implementation of rest days in live bird markets on the dynamics of H5N1 highly pathogenic avian influenza

Live bird markets (LBMs) act as a network ‘hub’ and potential reservoir of infection for domestic poultry. They may therefore be responsible for sustaining H5N1 highly pathogenic avian influenza (HPAI) virus circulation within the poultry sector, and thus a suitable target for implementing control strategies. We developed a stochastic transmission model to understand how market functioning impacts on the transmission dynamics. We then investigated the potential for rest days—periods during which markets are emptied and disinfected—to modulate the dynamics of H5N1 HPAI within the poultry sector using a stochastic meta-population model. Our results suggest that under plausible parameter scenarios, HPAI H5N1 could be sustained silently within LBMs with the time spent by poultry in markets and the frequency of introduction of new susceptible birds'' dominant factors determining sustained silent spread. Compared with interventions applied in farms (i.e. stamping out, vaccination), our model shows that frequent rest days are an effective means to reduce HPAI transmission. Furthermore, our model predicts that full market closure would be only slightly more effective than rest days to reduce transmission. Strategies applied within markets could thus help to control transmission of the disease.     

Outbreaks of H5N1 in poultry in Thailand: the relative role of poultry production types in sustaining transmission and the impact of active surveillance in control

H5N1, highly pathogenic avian influenza, continues to pose a public health risk in the countries of southeast Asia where it has become endemic. However, in Thailand, which experienced two of the largest recorded epidemics in 2004–2005, the disease has been successfully reduced to very low levels. We fitted a spatio-temporal model of the spread of infection to outbreak data collected during the second wave of outbreaks to assess the extent to which different poultry types were responsible for propagating infection. Our estimates suggest that the wave of outbreaks would not have been possible without the contribution of backyard flocks to the susceptibility of a sub-district. However, we also estimated that outbreaks involving commercial poultry, a much larger sector in Thailand than in neighbouring countries, were disproportionately infectious, a factor which was also crucial in sustaining the wave. As a result, implemented measures that aim to reduce the role of commercial farms in the spread of infection, such as the drive to bring aspects of the supply chain ‘in house’, may help to explain the subsequent success in controlling H5N1 in Thailand. We also found that periods of active surveillance substantially improved the rate of outbreak detection.     

Strategies for mitigating an influenza pandemic with pre-pandemic H5N1 vaccines

The recent worldwide spread of the swine-origin H1N1 2009 influenza outbreak has resulted in its designation as a pandemic by the World Health Organization. While it appears to result in mild symptoms, concern still exists that a more severe influenza pandemic with a high case fatality ratio might arise by reassortment or mutation of the currently circulating avian influenza (H5N1) virus. Given that recently developed candidate pre-pandemic H5N1 vaccines have shown potential for cross-strain protection, we investigated alternative vaccination strategies that exploit such vaccines using an agent-based simulation model of an actual community of approximately 30 000 people in a developed country. Assuming that a two-dose vaccination regimen would be required, we examined three vaccination strategies: pre-emptive, with vaccination applied prior to emergence of human-transmissible H5N1 influenza; reactive, where vaccination was initiated immediately after the first cases in the community were diagnosed; and a ‘split’ strategy where the first dose was administered pre-emptively during the pre-pandemic phase, with the second dose administered reactively. We showed that by effectively moving the delay between first and second doses into the pre-pandemic period, the split vaccination strategy achieved a substantially better attack rate reduction than the reactive strategy. Our results for an influenza strain with a reproduction number of 1.5 suggest reactive vaccination strategies that may be applicable to the current H1N1 2009 pandemic.     

Modelling the initial phase of an epidemic using incidence and infection network data: 2009 H1N1 pandemic in Israel as a case study

This paper presents new computational and modelling tools for studying the dynamics of an epidemic in its initial stages that use both available incidence time series and data describing the population''s infection network structure. The work is motivated by data collected at the beginning of the H1N1 pandemic outbreak in Israel in the summer of 2009. We formulated a new discrete-time stochastic epidemic SIR (susceptible-infected-recovered) model that explicitly takes into account the disease''s specific generation-time distribution and the intrinsic demographic stochasticity inherent to the infection process. Moreover, in contrast with many other modelling approaches, the model allows direct analytical derivation of estimates for the effective reproductive number (R_e) and of their credible intervals, by maximum likelihood and Bayesian methods. The basic model can be extended to include age–class structure, and a maximum likelihood methodology allows us to estimate the model''s next-generation matrix by combining two types of data: (i) the incidence series of each age group, and (ii) infection network data that provide partial information of ‘who-infected-who’. Unlike other approaches for estimating the next-generation matrix, the method developed here does not require making a priori assumptions about the structure of the next-generation matrix. We show, using a simulation study, that even a relatively small amount of information about the infection network greatly improves the accuracy of estimation of the next-generation matrix. The method is applied in practice to estimate the next-generation matrix from the Israeli H1N1 pandemic data. The tools developed here should be of practical importance for future investigations of epidemics during their initial stages. However, they require the availability of data which represent a random sample of the real epidemic process. We discuss the conditions under which reporting rates may or may not influence our estimated quantities and the effects of bias.     

既有中央空调系统如何应对"H1N1"病毒提出的挑战

介绍了“H1N1”病毒对空调系统带来的思考，提出了既有中央空调系统的应对措施，认为对空调系统应定期进行清洗、消毒，采用空气净化设备，或利用“光触媒”改善室内空气品质，使其向“健康空调”发展。     

Optimizing the early detection of low pathogenic avian influenza H7N9 virus in live bird markets

In Southeast Asia, surveillance at live bird markets (LBMs) has been identified as crucial for detecting avian influenza viruses (AIV) and reducing the risk of human infections. However, the design of effective surveillance systems in LBMs remains complex given the rapid turn-over of poultry. We developed a deterministic transmission model to provide guidance for optimizing AIV surveillance efforts. The model was calibrated to fit one of the largest LBMs in northern Vietnam at high risk of low pathogenic H7N9 virus introduction from China to identify the surveillance strategy that optimizes H7N9 detection. Results show that (i) using a portable diagnostic device would slightly reduce the number of infected birds leaving the LBM before the first detection, as compared to a laboratory-based diagnostic strategy, (ii) H7N9 detection could become more timely by sampling birds staying overnight, just before new susceptible birds are introduced at the beginning of a working day, and (iii) banning birds staying overnight would represent an effective intervention to reduce the risk of H7N9 spread but would decrease the likelihood of virus detection if introduced. These strategies should receive high priority in Vietnam and other Asian countries at risk of H7N9 introduction.     

既有中央空调系统如何应对“H1N1”病毒提出的挑战

介绍了“H1N1”病毒对空调系统带来的思考，提出了既有中央空调系统的应对措施，认为对空调系统应定期进行清洗、消毒，采用空气净化设备，或利用“光触媒”改善室内空气品质，使其向“健康空调”发展。     

共表达H5、H7亚型AIV HA基因与鸡IL-18基因的重组鸡痘病毒构建

以鸡痘病毒(FPV)疫苗株为载体,将H5和H7亚型禽流感病毒血凝素(AIV HA)基因串联后(拥有同一个阅读框)和鸡白细胞介素-18(IL-18)基因分别插入到鸡痘病毒表达载体pUTA-16-LacZ复合启动子(ATI-P7.5×20)和单一启动子1(P7.5)下游,构建了携带AIV HA基因和鸡白细胞介素-18基因的重组鸡痘病毒转移载体质粒pUTAL-H5-H7-IL18;用相同的方法构建重组鸡痘病毒转移载体质粒pUTAL-H5-IL18;将H5亚型AIV HA基因插入到鸡痘病毒表达载体pUTA2复合启动子(ATI-P7.5×20)下游,构建了携带H5亚型AIV HA基因的重组鸡痘病毒转移载体质粒pUTA2-H5.应用脂质体转染法,将重组鸡痘病毒转移载体质粒与282E4株鸡痘病毒共转染鸡胚成纤维细胞(CEF),经BrdU进行三次加压蚀斑筛选后,以不同代次的细胞mRNA为模板,利用H5亚型AIV HA基因、H7亚型AIV HA基因和鸡IL-18基因特异引物进行RT-PCR和蛋白印迹检测,筛选出H5HA-H7HA融合蛋白基因和鸡IL-18基因共表达的重组鸡痘病毒rFPV-H5HA-H7HA-IL18,H5亚型AIV HA基因和鸡IL-18基因共表达的重组鸡痘病毒rFPV-H5HA-IL18以及单独表达H5亚型AIV HA基因的重组鸡痘病毒rFPV-H5HA.这些重组鸡痘病毒的构建为AIV活载体疫苗的研制奠定了基础.     

N,N-双四唑胺的合成工艺改进与研究

以双氰胺钠和叠氮化钠为主要原料,加热分子内环化得到N,N-双四唑胺,并采用IR、NMR、MS等方法,对产品结构表征。探讨了N,N-双四唑胺合成反应机理,考察了溶液酸碱性、反应温度及反应时间等关键因素对结果的影响,获得适宜反应条件:摩尔比为n(C2N3Na)n(Na N3)n(HCl)=121,在T=60℃,调节p H=3后,加热至100℃反应24 h,冷却至10℃左右,调节p H=2,产率达89.5%,纯度可达99%。     

微信H5广告后情感表现类型实证研究

目的 构建微信H5广告后情感评价量表及其标准,并通过调查分析验证微信H5广告中具有后情感艺术表现形式的假设。方法 首先,界定研究对象为微信H5广告,并对研究设备进行评估和测量;其次,根据抽样方法抽取广告样本,并进行类型化分析;最后,采用定量研究方法,对微信H5广告进行后情感量表调查与评价,并通过数据分析对假设进行验证。结果 游戏、测试、生成和视频四种类型的微信H5广告具有后情感化设计形式与特征,研究结果验证了有关微信H5广告中的后情感表现形式的假设,也证实了这种新的后情感表现形式存在于新媒体广告中。结论 该方法构建了后情感评价量表及其标准,为微信H5广告的后情感化设计提供了一种可借鉴参考的方法,并建立了新媒体广告设计与后情感之间相互关联的全新视角。     

Rapid and Quantitative Detection of Avian Influenza A(H7N9) Virions in Complex Matrices Based on Combined Magnetic Capture and Quantum Dot Labeling

Avian influenza A(H7N9) virus, which emerged in China in the spring of 2013, has infected hundreds of people and resulted in many deaths. Herein, a rapid and quantitative assay is proposed for the one‐step detection of H7N9 virions. Immunomagnetic nanospheres (IMNs) and antibody‐conjugated quantum dots (Ab‐QDs) are simultaneously employed to capture and identify the target virus, leading to a high efficiency, good specificity, and strong anti‐interference ability. Moreover, this reliable detection assay, which combines the efficient magnetic enrichment and the unique photophysical properties of QDs, can achieve a high sensitivity for a low detection limit. At the same time, this detection strategy shows great flexibility for employment in a variety of fluorescence detectors, including fluorescence spectrometry, microscope assays, and handheld UV lamp tests. Furthermore, our one‐step detection strategy induces very little change in the integrity of the vulnerable virions, which enables additional genotyping testing following the fluorescence detection. The present study, thus, reports a rapid and quantitative approach for the detection of H7N9 virions based on simultaneous magnetic capture and QD labeling, thereby providing a higher probability for detection and therefore faster diagnosis of H7N9‐infected patients.     

Spatial dynamics of the 1918 influenza pandemic in England,Wales and the United States

There is still limited understanding of key determinants of spatial spread of influenza. The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale.To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US. Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities. We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence. We inferred the most likely transmission trees for both countries.For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison. Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread. For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only. We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty.     

高速列车A7N01S-T5铝合金应力腐蚀行为研究

文章选取了我国某类型高速列车常用的A7N01S-T5铝合金材料,进行了恒载荷应力腐蚀试验,对A7N01S-T5材料的应力腐蚀机理、应力腐蚀强度因子K1SCC和裂纹生长机制进行了研究.结果表明,A7N01S-T5铝合金的应力腐蚀破坏敏感性很高,其临界应力场强度因子K1 SCC为5.2 MPa.m1/2,仅为断裂韧度K1 C的0.15,对应的临界应力门槛值б为123MPa,仅为拉伸强度бb0.27.裂纹断口面有明显的舌状凸起和凹坑的存在.A7N01S-T5铝合金的应力腐蚀裂纹以沿晶开裂为主,形貌呈树枝状,同时相邻二次裂纹之间有竞争生长的关系.     

Uncovering the Rab5‐Independent Autophagic Trafficking of Influenza A Virus by Quantum‐Dot‐Based Single‐Virus Tracking

Autophagy is closely related to virus‐induced disease and a comprehensive understanding of the autophagy‐associated infection process of virus will be significant for developing more effective antiviral strategies. However, many critical issues and the underlying mechanism of autophagy in virus entry still need further investigation. Here, this study unveils the involvement of autophagy in influenza A virus entry. The quantum‐dot‐based single‐virus tracking technique assists in real‐time, prolonged, and multicolor visualization of the transport process of individual viruses and provides unambiguous dissection of the autophagic trafficking of viruses. These results reveal that roughly one‐fifth of viruses are ferried into cells for infection by autophagic machineries, while the remaining are not. A comprehensive overview of the endocytic‐ and autophagic‐trafficking process indicates two distinct trafficking pathway of viruses, either dependent on Rab5‐positive endosomes or autophagosomes, with striking similarities. Expressing dominant‐negative mutant of Rab5 suggests that the autophagic trafficking of viruses is independent on Rab5. The present study provides dynamic, precise, and mechanistic insights into the involvement of autophagy in virus entry, which contributes to a better understanding of the relationship between autophagy and virus entry. The quantum‐dot‐based single‐virus tracking is proven to hold promise for autophagy‐related fundamental research.     

添加剂和烧结工艺对A1N瓷性能的影响

本文研究了Ｙ２Ｏ３，ＣａＯ，Ｅｒ２Ｏ３，Ｙｂ２Ｏ３等不同添加剂，烧结温度及保温时间对Ａ１Ｎ瓷导热率，致密性及介电性能的影响，并从显微结构及理论上解释了影响导热率高低及介电性能好坏的原因。     

Spatial stochastic modelling of the Hes1 gene regulatory network: intrinsic noise can explain heterogeneity in embryonic stem cell differentiation

Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. The noisy cyclic expression of Hes1 and its downstream genes are known to be responsible for this, but the mechanism underlying this variability in expression is not well understood. In this paper, we show that the observed experimental data and diverse differentiation responses can be explained by a spatial stochastic model of the Hes1 gene regulatory network. We also propose experiments to control the precise differentiation response using drug treatment.     

用N2O-C2H2火焰原子吸收光谱法测定电解液中锂

简述运用N2O-C2H2火焰原子吸收光谱法进行镉镍电池电解液中锂含量的测定，并介绍了锂最佳测定条件及呈良好线性范围的浓度。同时对样品的干扰因素、消化处理条件，在综合分析的基础上提出了有效的测定方案。该测定方法灵敏度好，准确度与精密度均能满足镉镍电池研制工作的要求。测定样品锂含量相对标准偏差均小于1．0％（测定次数n=10），标准加入回收率均在97．0％，100．0％（n=6）范围内，达到了实验室分析质量与质量控制的要求，适用于电解液中锂含量的控制分析和样品系统分析。     

模拟油田H2S/CO2环境中N80钢的腐蚀及影响因素研究

模拟实际含H2S／CO2高温高压井下多相腐蚀环境，研究了不同腐蚀影响因素对N80钢的作用规律。结果表明：在所研究的参数范围内，材料表现出较高的均匀腐蚀速率，且伴有不同程度的局部腐蚀。当其他条件保持相同时，随H2S含量的增加，材料的腐蚀速率先增加后降低；当介质中CO2含量增加时，腐蚀速率则呈单调增大趋势；Ca^2 、Mg^2 的影响与CO2类似，而Cl^-的影响则与H2S具有基本相似的规律。在H2S／CO2混合介质中，N80钢的腐蚀行为受各因素的交互影响，且影响程度不同，各因素作用由大到小依次是：H2S含量、Ca^2 、Mg^2 含量、Cl^-浓度和CO2含量。     

Preventable H5N1 avian influenza epidemics in the British poultry industry network exhibit characteristic scales

Epidemics are frequently simulated on redundantly wired contact networks, which have many more links between sites than are minimally required to connect all. Consequently, the modelled pathogen can travel numerous alternative routes, complicating effective containment strategies. These networks have moreover been found to exhibit ‘scale-free’ properties and percolation, suggesting resilience to damage. However, realistic H5N1 avian influenza transmission probabilities and containment strategies, here modelled on the British poultry industry network, show that infection dynamics can additionally express characteristic scales. These system-preferred scales constitute small areas within an observed power law distribution that exhibit a lesser slope than the power law itself, indicating a slightly increased relative likelihood. These characteristic scales are here produced by a network-pervading intranet of so-called hotspot sites that propagate large epidemics below the percolation threshold. This intranet is, however, extremely vulnerable; targeted inoculation of a mere 3–6% (depending on incorporated biosecurity measures) of the British poultry industry network prevents large and moderate H5N1 outbreaks completely, offering an order of magnitude improvement over previously advocated strategies affecting the most highly connected ‘hub’ sites. In other words, hotspots and hubs are separate functional entities that do not necessarily coincide, and hotspots can make more effective inoculation targets. Given the ubiquity and relevance of networks (epidemics, Internet, power grids, protein interaction), recognition of this spreading regime elsewhere would suggest a similar disproportionate sensitivity to such surgical interventions.     

Quantifying selection and diversity in viruses by entropy methods, with application to the haemagglutinin of H3N2 influenza

Many viruses evolve rapidly. For example, haemagglutinin (HA) of the H3N2 influenza A virus evolves to escape antibody binding. This evolution of the H3N2 virus means that people who have previously been exposed to an influenza strain may be infected by a newly emerged virus. In this paper, we use Shannon entropy and relative entropy to measure the diversity and selection pressure by an antibody in each amino acid site of H3 HA between the 1992–1993 season and the 2009–2010 season. Shannon entropy and relative entropy are two independent state variables that we use to characterize H3N2 evolution. The entropy method estimates future H3N2 evolution and migration using currently available H3 HA sequences. First, we show that the rate of evolution increases with the virus diversity in the current season. The Shannon entropy of the sequence in the current season predicts relative entropy between sequences in the current season and those in the next season. Second, a global migration pattern of H3N2 is assembled by comparing the relative entropy flows of sequences sampled in China, Japan, the USA and Europe. We verify this entropy method by describing two aspects of historical H3N2 evolution. First, we identify 54 amino acid sites in HA that have evolved in the past to evade the immune system. Second, the entropy method shows that epitopes A and B on the top of HA evolve most vigorously to escape antibody binding. Our work provides a novel entropy-based method to predict and quantify future H3N2 evolution and to describe the evolutionary history of H3N2.