为药理学事业奋斗的一生

编者按 王永铭教授是改革开放后首批赴国外研修药物不良反应监测与合理用药的临床药理学家,回国后率先开展药物不良反应和药物流行病学研究,组织开展学术交流,对推动我国药物不良反应监测制度及机构建设作出突出贡献.他科学求实、勇于创新的精神,值得我们学习.     

一辈子热爱药理事业

编者按 胥彬教授是我国一位著名的药理学家,他致力于抗癌药物的开发与研究,取得显著社会效益和经济效益,享有国际声誉.胥教授虽已年届八旬,但仍不断学习新知识,继续为抗癌事业做贡献.他积极的人生态度和宽容豁达的人生境界,令人钦敬.     

Analysis of the shelf life and transfusion life of whole blood and erythrocyte concentrates

The shelf life of 60,000 units of whole blood and red cell concentrates in the blood center were analysed before delivering to hospitals as well as the transfusion age of 18,000 units in relation to the stock-size and the outdated units. The mean transfusion age of whole blood units and red blood cell concentrates amounted to 11 to 12 days and 16 to 17 days, respectively. The shelf life of blood transfused within 24 hours after collection was 1.6% and 3.8% transfused within 48 hours according to the total number of whole blood and red blood cell concentrates. Washed red cell concentrates were prepared from buffy coat-free resuspended red cell concentrates on an average at the 7th day of storage. A high stock-size of about 1,000 units rather than of 600 units in the blood center increased the shelf life and also the number of outdated units from less than 0.5% up to more than 3%.     

Cumulative weather effects can impact across the whole life cycle

Predicting how species will be affected by future climatic change requires the underlying environmental drivers to be identified. As vital rates vary over the lifecycle, structured population models derived from statistical environment–demography relationships are often used to inform such predictions. Environmental drivers are typically identified independently for different vital rates and demographic classes. However, these rates often exhibit positive temporal covariance, suggesting that vital rates respond to common environmental drivers. Additionally, models often only incorporate average weather conditions during a single, a priori chosen time window (e.g. monthly means). Mismatches between these windows and the period when the vital rates are sensitive to variation in climate decrease the predictive performance of such approaches. We used a demographic structural equation model (SEM) to demonstrate that a single axis of environmental variation drives the majority of the (co)variation in survival, reproduction, and twinning across six age–sex classes in a Soay sheep population. This axis provides a simple target for the complex task of identifying the drivers of vital rate variation. We used functional linear models (FLMs) to determine the critical windows of three local climatic drivers, allowing the magnitude and direction of the climate effects to differ over time. Previously unidentified lagged climatic effects were detected in this well‐studied population. The FLMs had a better predictive performance than selecting a critical window a priori, but not than a large‐scale climate index. Positive covariance amongst vital rates and temporal variation in the effects of environmental drivers are common, suggesting our SEM–FLM approach is a widely applicable tool for exploring the joint responses of vital rates to environmental change.     

Seed size and plant strategy across the whole life cycle

We compiled information from the international literature to quantify the relationships between seed mass and survival through each of the hazards plants face between seed production and maturity. We found that small-seeded species were more abundant in the seed rain than large-seeded species. However, this numerical advantage was lost by seedling emergence. The disadvantage of small-seeded species probably results from size-selective post-dispersal seed predation, or the longer time small-seeded species spend in the soil before germination. Seedlings from large-seeded species have higher survival through a given amount of time as seedlings. However, this advantage seems to be countered by the greater time taken for large-seeded species to reach reproductive maturity: our data suggested no relationship, or perhaps a weak negative relationship, between seed size and survival from seedling emergence through to adulthood. A previous compilation showed that the inverse relationship between seed mass and the number of seeds produced per unit canopy area per year is countered by positive relationships between seed mass, plant size and plant longevity. Taken together, these data show that our old understanding of a species' seed mass as the result of a trade–off between producing a few large offspring, each with high survival probability, versus producing many small offspring each with a lower chance of successfully establishing was incomplete. It seems more likely that seed size evolves as part of a spectrum of life history traits, including plant size, plant longevity, juvenile survival rate and time to reproduction.     

马铃薯全生育期内根际微生物组变化规律

[目的]陆生植物根际环境与土壤中的微生物菌群关系密切,其根际微生物群落动态极可能直接影响着植物健康及养分高效利用。虽然根际益生菌已被证实可用于提高作物生产力,但由于缺乏对这些菌群组成动态变化规律的认识了解,它们的开发受到限制。研究马铃薯全生育期根际菌群的动态变化规律,探讨根际菌群变化与马铃薯发育时期的相关性,为针对马铃薯不同生长时期开发专用生物益生菌肥奠定理论基础。[方法]本研究着眼于马铃薯田间全生命周期微生物组动态变化,通过Illumina MiSeq高通量测序技术对不同时间点马铃薯根际细菌16S rRNA基因V3-V4区和真菌ITS区测序并对操作分类单位(OTU)进行聚类,分析样品间微生物群落的多样性特征,并通过机器学习的方法建立模型,将根际菌群与田间马铃薯发育时间相关联。[结果]根际菌群在马铃薯各个发育阶段随时间变化明显,营养生长阶段的微生物群落结构发生了显著变化,随着结薯期的开始逐渐稳定,直到块茎成熟后期根际菌群再次出现较大变化,且在不同施肥处理间呈现较大差异。进一步基于模型挖掘了与马铃薯发育时间相关联的22个特征细菌类群和16个特征真菌类群,其中苗期和结薯末期的特征类群分别为梭菌(Clostridium)和放线菌(Actinobacteria)。[结论]马铃薯的生长发育时期是影响根际微生物群落组成的主要因素,益生菌肥的添加主要影响马铃薯结薯末期的细菌微生物菌群结构。     

A parametric whole life cost model for offshore wind farms

Purpose

Life cycle cost (LCC) considerations are of increasing importance to offshore wind farm operators and their insurers to undertake long-term profitable investments and to make electricity generation more price-competitive. This paper presents a cost breakdown structure (CBS) and develops a whole life cost (WLC) analysis framework for offshore wind farms throughout their life span (～25 years).

Methods

A combined multivariate regression/neural network approach is developed to identify key cost drivers and evaluate all the costs associated with five phases of offshore wind projects, namely pre-development and consenting (P&C), production and acquisition (P&A), installation and commissioning (I&C), operation and maintenance (O&M) and decommissioning and disposal (D&D). Several critical factors such as geographical location and meteorological conditions, rated power and capacity factor of wind turbines, reliability of sub-systems and availability and accessibility of transportation means are taken into account in cost calculations. The O&M costs (including the cost of renewal and replacement, cost of lost production, cost of skilled maintenance labour and logistics cost) are assessed using the data available in failure databases (e.g. fault logs and O&M reports) and the data supplied by inspection agencies. A net present value (NPV) approach is used to quantify the current value of future cash flows, and then, a bottom-up estimate of the overall cost is obtained.

Results and discussion

The proposed model is tested on an offshore 500-MW baseline wind farm project, and the results are compared to experimental ones reported in the literature. Our results indicate that the capital cost of wind turbines and their installation costs account for the largest proportion of WLC, followed by the O&M costs. A sensitivity analysis is also conducted to identify those factors having the greatest impact on levelized cost of energy (LCOE).

Conclusions

The installed capacity of a wind farm, distance from shore and fault detection capability of the condition monitoring system are identified as parameters with significant influence on LCOE. Since the service lifetime of a wind farm is relatively long, a small change in interest rate leads to a large variation in the project’s total cost. The presented models not only assist stakeholders in evaluating the performance of ongoing projects but also help the wind farm developers reduce their costs in the medium–long term.

     

ISHAN: sequence homology analysis package

Sequence based homology studies play an important role in evolutionary tracing and classification of proteins. Various methods are available to analyze biological sequence information. However, with the advent of proteomics era, there is a growing demand for analysis of huge amount of biological sequence information, and it has become necessary to have programs that would provide speedy analysis. ISHAN has been developed as a homology analysis package, built on various sequence analysis tools viz FASTA, ALIGN, CLUSTALW, PHYLIP and CODONW (for DNA sequences). This JAVA application offers the user choice of analysis tools. For testing, ISHAN was applied to perform phylogenetic analysis for sets of Caspase 3 DNA sequences and NF-kappaB p105 amino acid sequences. By integrating several tools it has made analysis much faster and reduced manual intervention.     

RefPlus: an R package extending the RMA Algorithm

RMA has become a widely used methodology to pre-process Affymetrix gene expression microarrays. A limitation of RMA is that the calculated probeset intensities change when a set of microarrays is re-pre-processed after the inclusion of additional microarrays into the analysis set. Here we report the availability of the RefPlus package containing functions to perform the Extrapolation Strategy and Extrapolation Averaging algorithms which address these issues. AVAILABILITY: The software is implemented in the R language and can be downloaded from the Bioconductor project website (http://www.bioconductor.org). SUPPLEMENTARY INFORMATION: Further details of the workings and evaluation of these functions are given in the documentation available on the Bioconductor website.     

The IronChip evaluation package: a package of perl modules for robust analysis of custom microarrays

Background  

Gene expression studies greatly contribute to our understanding of complex relationships in gene regulatory networks. However, the complexity of array design, production and manipulations are limiting factors, affecting data quality. The use of customized DNA microarrays improves overall data quality in many situations, however, only if for these specifically designed microarrays analysis tools are available.     

Screening the human exome: a comparison of whole genome and whole transcriptome sequencing

Background  

There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important.     

BBMV: an R package for the estimation of macroevolutionary landscapes

The distribution of traits along phylogenies bears signatures of how ecological and evolutionary processes have interacted to influence phenotypic evolution, which can be deciphered using macroevolutionary models. BBMV implements a model for the evolution of continuous characters on phylogenies that generalizes existing ones, like Brownian motion and the Ornstein‐Uhlenbeck model. In this model quantitative characters evolve under both random diffusion and a deterministic force that can be of any possible shape and strength. The model can be used to infer evolutionary scenarios that remained inaccessible so far, like directional trends, disruptive selection, and even bounded evolution. With this new tool at hand, researchers will be able to test complex hypothesis‐driven scenarios regarding trait evolution, but they will also have the possibility to estimate the shape of the adaptive landscapes in which traits evolved. Ultimately, this will provide a way to infer how ecological processes have influenced phenotypic evolution over long timescales. The BBMV package is implemented in the R statistical language and is freely available on the CRAN repository < https://CRAN.R‐project.org/package=BBMV >. All source code can also be found on < https://github.com/fcboucher/BBMV >, along with a detailed tutorial.