Progress and challenges for malaria vaccines

Malaria causes much physical and economic hardship in tropical regions, particularly in communities where medical care is rudimentary. Should a vaccine be developed, it is the residents of these areas that stand to benefit the most. But the vaccine, which has been promised to be 'just round the corner' for many years, remains elusive. It is important to ask why this is so, when effective vaccines exist for many other infectious diseases. What are the reasons for the slow rate of progress, and what has been learned from the first clinical trials of candidate malaria vaccines? What are the remaining challenges, and what strategies can be pursued to address them?     

The publication-citation matrix and its derived quantities

We give an overview of the main data of a publication-citation matrix. We show how impact factors are defined, and, in particular, point out the difference between the synchronous and the diachronous impact factor. The advantages and disadvantages of using both as tools in research evaluation are discussed.     

多伦多地区温度与臭氧剖面的激光雷达与SAGEⅡ卫星测量结果比较分析（Ⅰ）

对加拿大多伦多地区SAGEⅡ卫星及激光雷达探测资料,对2种观测系统所获得的大气温度及臭氧垂直分布进行了比较分析.结果表明①由2种观测系统测量的温度廓线有很好的一致性,特别是在15.5～35.5*!km的垂直区间;②在15.5～40.5*!km的垂直区间,2种观测系统的臭氧混合比的绝对误差的变化范围体积分数是±2×10-6;③大约35*!km以下,由激光雷达获得的臭氧数密度具有较高的精度,反之类推.特别,在包括臭氧数密度极大值层的21.5～35.5*!km范围内,8个剖面平均的相对误差趋于零,其垂直平均值为0.96±7.64%(1σ).     

Chronological evidence that the Moon is either young or did not have a global magma ocean

Chemical evolution of planetary bodies, ranging from asteroids to the large rocky planets, is thought to begin with differentiation through solidification of magma oceans many hundreds of kilometres in depth. The Earth's Moon is the archetypical example of this type of differentiation. Evidence for a lunar magma ocean is derived largely from the widespread distribution, compositional and mineralogical characteristics, and ancient ages inferred for the ferroan anorthosite (FAN) suite of lunar crustal rocks. The FANs are considered to be primary lunar flotation-cumulate crust that crystallized in the latter stages of magma ocean solidification. According to this theory, FANs represent the oldest lunar crustal rock type. Attempts to date this rock suite have yielded ambiguous results, however, because individual isochron measurements are typically incompatible with the geochemical make-up of the samples, and have not been confirmed by additional isotopic systems. By making improvements to the standard isotopic techniques, we report here the age of crystallization of FAN 60025 using the (207)Pb-(206)Pb, (147)Sm-(143)Nd and (146)Sm-(142)Nd isotopic systems to be 4,360?±?3 million years. This extraordinarily young age requires that either the Moon solidified significantly later than most previous estimates or the long-held assumption that FANs are flotation cumulates of a primordial magma ocean is incorrect. If the latter is correct, then much of the lunar crust may have been produced by non-magma-ocean processes, such as serial magmatism.     

A conditional knockout resource for the genome-wide study of mouse gene function

Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.     

Oxysterols direct B-cell migration through EBI2

EBI2 (also called GPR183) is an orphan G-protein-coupled receptor that is highly expressed in spleen and upregulated upon Epstein-Barr-virus infection. Recent studies indicated that this receptor controls follicular B-cell migration and T-cell-dependent antibody production. Oxysterols elicit profound effects on immune and inflammatory responses as well as on cholesterol metabolism. The biological effects of oxysterols have largely been credited to the activation of nuclear hormone receptors. Here we isolate oxysterols from porcine spleen extracts and show that they are endogenous ligands for EBI2. The most potent ligand and activator is 7α,25-dihydroxycholesterol (OHC), with a dissociation constant of 450?pM for EBI2. In vitro, 7α,25-OHC stimulated the migration of EBI2-expressing mouse B and T cells with half-maximum effective concentration values around 500 pM, but had no effect on EBI2-deficient cells. In vivo, EBI2-deficient B cells or normal B cells desensitized by 7α,25-OHC pre-treatment showed reduced homing to follicular areas of the spleen. Blocking the synthesis of 7α,25-OHC in vivo with clotrimazole, a CYP7B1 inhibitor, reduced the content of 7α,25-OHC in the mouse spleen and promoted the migration of adoptively transferred pre-activated B cells to the T/B boundary (the boundary between the T-zone and B-zone in the spleen follicle), mimicking the phenotype of pre-activated B cells from EBI2-deficient mice. Our results show an unexpected causal link between EBI2, an orphan G-protein-coupled receptor controlling B-cell migration, and the known immunological effects of certain oxysterols, thus uncovering a previously unknown role for this class of molecules.     

From Bureaucracy to Learning Organization: Critical Minimum Specification Design as Space for Sensemaking

What does it take of a municipal organization to be a significant participant in the dynamic, learning oriented interaction within a triple helix constellation of partners aimed at regional development? The short answer is that it needs to develop the receptivity (Morgan, 1996) and the flexibility to act in novel ways, which are the traits of a learning organization. However, how these abilities are enhanced in organizations that are basically organized as bureaucracies aimed at maintaining a stable and standardized function of its operations, is an under-researched phenomenon within the triple helix discussions. In this paper, I investigate this question through an analysis of a change and development process within a municipal organization that aimed to enhance the capacity of the organization to interact receptively and dynamically with their environment, by changing their organizational structure from a bureaucratic to a post-bureaucratic type. The main finding is that rather than the new formal structure as such; it is the process of sensemaking following the introduction of this new formal structure that creates the capacity for learning and development. However, this outcome is dependent on the sensemaking process being turned over from a defensive mode into a learning oriented mode. The paper explores how this turn may be facilitated.     

Tycho brahe in china: the Jesuit mission to Peking and the iconography of European instrument-making processes

In the late 1660s, Ferdinand Verbiest, a Flemish Jesuit missionary in Peking, was instructed to re-equip the Imperial Observatory. The new instruments which he caused to be built were modelled neither upon contemporary European prototypes, nor those of traditional Chinese astronomy, but on the pieces in Tycho Brahe's Mechanica, of eighty years before. The Chinese instruments were lavishly illustrated, moreover, in 105 woodcuts that contained detailed representations of their processes of construction. It is argued that these illustrations not only give us valuable insights into what the technical Jesuits did in Peking, but show how sixteenth- and seventeenth-century European craftsmen constructed their instruments, for while the location was Oriental, the technology was Western. They can also give important insights into how Tycho's prototypes had been built, and provide us with useful information regarding European instrument-making technology.