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.     

基于HCR放大的无标记型荧光传感器的构建及H5N1 DNA检测

对于高致病性H5N1禽流感病毒,构建检测该病毒的高灵敏生物传感器,并与智能包装相结合用于实时监测,这对禽流感的防控具有重要意义。基于杂交链式反应（HCR）信号放大策略,以AgNCs作为荧光信号基团,构建了一种无标记“turn on”型荧光生物传感器用于检测代表H5N1病毒的H5N1基因序列。该传感器以H5N1 DNA作为触发剂引发HCR过程,使AgNCs产生强的荧光信号变化。研究表明,当H5N1 DNA浓度在0.2~800.0 nmol/L内,该传感器具有良好的响应信号,且在0.2~200.0 nmol/L之间的荧光强度与H5N1 DNA浓度呈线性相关,线性方程为y=10.982C+567.435（R2=0.992 73）,检测限为176 pmol/L。核酸传感体系具有通用性,通过简单调整目标序列,可实现对不同目标物的特异性灵敏检测。该研究有望为高灵敏分析禽流感病毒标志物的通用传感平台设计提供思路。     

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%。     

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.     

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。     

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.     

C3H8O3在ZAlSi12Cu2Mg1微弧氧化膜形成中作用机理的研究

在含Na2SiO38g/L、NaOH 2g/L、Na2WO42g/L、Na2EDTA 2g/L的电解液和正/负向电压取480/130V的条件下,通过改变C3H8O3的含量,对ZAlSi12Cu2Mg1进行微弧氧化处理。研究结果发现,添加C3H8O3可明显地细化电解液中的胶粒,改善微弧氧化膜的致密性和平整性,增加膜层厚度,提高膜层硬度。当C3H8O3的含量由0mL/L增加到10mL/L时,胶粒的平均粒径从10530.6nm几乎线性减小到2615.8nm,膜层氧化物颗粒尺寸变小,致密层所占比例增加,膜层厚度从63μm增加到156μm,膜层硬度提高到894HV;而含量超过10mL/L时,临界起弧正向电压升高至408V。电解液中加入C3H8O3,膜层中除了莫来石相,还出现了α-Al2O3、γ-Al2O3、WO3和SiO2相。     

4Cr5MoSiV1，8407钢的热疲劳性能

采用自约束热疲劳试验方法,对比研究了相同热处理条件的4Cr5MoSiV1,8407钢的热疲劳特性,观察分析了疲劳裂纹形貌和深度,采用热疲劳损伤因子定量研究了二种钢的热疲劳过程。结果表明：两种钢的热疲劳裂纹萌生发生在100－200次之间。8407钢热疲劳裂纹的萌生较4Cr5MoSiV1钢均匀,细小;在1600次冷热循环前,二者的热疲劳损伤程度无明显差别,在1600次热循环后,前者的热疲劳损伤程度低于后者;在较低的回火温度条件下,8407钢的热疲劳抗力稍优于4Cr5MoSiV1;而在高温回火时,8407钢的热疲劳抗力属于4Cr5MoSiV1钢。分析了这二种钢的热疲劳机制,指出决定材料热疲劳裂纹抗力的是钢的热稳定性和钢的强度或硬度。     

N80油管钢在CO_2/H_2S水介质中的腐蚀研究

油田设施受产出水和CO2/H2S腐蚀严重.以长庆某天然气井产出水为腐蚀介质,采用失重法研究了不同腐蚀影响因素对N80钢的作用规律.结果表明,随着介质温度的升高,腐蚀速率先增加后降低,并在60℃时达到最大;Cl-的影响与温度具有基本相似的规律,在Cl-含量为30 g/L时腐蚀速率最大;随着pH值的增大,腐蚀速率持续减小,并在pH值为8.0左右时达到最低;随着CO:分压的增大,腐蚀速率呈单调增大趋势;随着H2S分压的增大,腐蚀速率先下降后又缓慢升高.     

基于L2-投影及日H1-投影进行不可压缩粘性流体数值模拟的比较:案例分析

本文的主要目的是讨论不可压缩粘性流体的Navier-Stokes方程的数值模拟.本文所用的方法足对时间用一阶精度算子分裂离散化,对空间度是用Uzawa方法对L2-投影及日H<,1>-投影求解Stokes问题,以及利用类波动方程方法求解平流问题.这两种投影格式都很容易实现.我们利用它们求解经典顶盖驱动方腔流问题直至雷诺数7500都取得了一致结果.当雷诺数处十区间[8575,8590](对应[8600,8625])时,运用L2-投影(对戍H1投影)得到的结果具有时间周期性,这表明Hopf分支的产生.当雷诺数为10000时,存在两个主导频率相互作用.     

不同热处理方法对1J50合金软磁性能影响研究

1J50软磁合金良好的磁性能主要是通过合适的热处理工艺方法得到的,用金相显微镜、XRD等对不同热处理工艺的1J50软磁合金的组织结构进行了分析,用MATS - 2010SA软磁测试仪对1J50软磁合金的磁性能进行了检测.结果表明,不同热处理工艺方法得到的1J50软磁合金组织和性能存在比较明显的差异.氢气气氛热处理得到的合金软磁性能优异.     

H_2气氛保护热处理1J50组织结构与性能的研究

1J50软磁合金的性能主要是通过H2热处理获得的,在1130℃和H2气氛保护下对冷轧态1J50软磁合金进行了热处理。运用MATS-2010SA软磁测试仪对处理前后1J50软磁合金的磁性能进行了检测,运用金相显微镜、XRD等手段对处理前后1J50软磁合金的组织结构进行了分析。结果表明,通过H2热处理,1J50软磁合金的矫顽力显著降低,起始磁导率和最大磁导率提高;组织结构发生明显变化,冷轧态1J50软磁合金组织为孪晶奥氏体,平均晶粒尺寸为200μm,处理过后,晶粒显著长大,平均晶粒尺寸为100μm;由于在600℃时采取了快冷,处理后1J50软磁合金中未出现大量FeNi相和FeNi3相。