The 2006 Benjamin Franklin Medal in Chemistry presented to Samuel J. Danishefsky, Ph.D.

Organic synthesis of natural products began in 1828 with Wohler's synthesis of urea, the first time a substance derived from a living organism had been produced by combining inorganic materials. Progress in the field was slow at first, due to the limited purification and analytical methods. Advances in those areas gave rise to rapid progress in synthesis, as chemists could now focus their energies on devising new approaches to the preparation of increasingly complex molecules. While it is possible to prepare many molecules by using known chemistry in new combinations, real progress has been the result of keen insight and creativity on the part of only a few individuals.Professor Samuel J. Danishefsky established himself early on as a leader in this field when he recognized that a well-known ring forming reaction could be greatly extended by adding chemical functionality to one of the components. He then found that these new reactive components could react with heretofore unreactive components to produce new rings containing oxygen atoms both in the ring and as attachments to the ring. These products were very similar to naturally occurring sugars. Danishefsky realized that he could develop this chemistry further to produce precisely defined polysaccharides as well. Some of these polysaccharides occur on the surface of cancer cells. Using the chemistry he developed, he was able to prepare these cancer cell markers, and after combining them with certain proteins, showed that the resulting molecules behaved as cancer vaccines. Several have entered clinical trial.Danishefsky has synthesized many other natural products, but he is particularly interested in those that may be useful in treating cancer. His syntheses allow for the modification of the final product in ways that improve both safety and efficacy. Several of these compounds have also entered clinical trials. Thus his work has not only advanced the art and science of organic synthesis, but stands to make dramatic advances in the treatment of cancer as well.     

Split genes

Contrary to what Jacques Monod affirmed in the 1960s, it is now known that what is true of the bacterium is not true of the elephant. In particular, it was discovered in 1977 that the genes of the higher organisms are split into segments, instead of being continuous as is the case with, for example, Escherichia coli. What is the significance of this split structure and how do organisms manage to gather together the useful parts of their genes and to eliminate those which are surplus? This article reviews what is already certain in this field and comments on the most recent prospects opened up by the discovery of genes ‘in pieces’.     

The 2001 Benjamin Franklin medal in physics presented to Alan Guth, Ph.D. of Cambridge, Massachusetts

The Franklin Institute, Philadelphia, Pennsylvania, awarded the 2001 Benjamin Franklin Medal in Physics to Alan H. Guth for his efforts to advance our knowledge of physical science and its application of the inflationary scenario, in which the universe undergoes a rapid expansion in the first stages of the Big Bang.     

Control mechanisms governing protein-protein interactions in assemblies

The study of the assembly and maturation of bacteriophages allows us to investigate biological control mechanisms which act on the level of proteins. Such studies complement those on the now well known mechanisms which operate on the level of switching on or switching off the expression of genes. The present paper explains what has been learned about how protein interactions are stimulated sequentually by conformational changes. It also discusses our understanding of how the shape of a virus is determined by the proteins involved.     

The 2007 Benjamin Franklin medal in materials engineering, Presented to Merton C. Flemings, Sc.D., Massachusetts Institute of Technology, Cambridge, Massachusetts

The second half of the twentieth century marked the emergence of metal casting, also known as solidification processing, as a field for scientific and engineering inquiry. Merton C. Flemings is recognized internationally for his pioneering work in this field resulting in the development of fundamental understanding and novel processes of commercial importance. Amongst his work is semi-solid metalworking (SSM), an environmentally friendly process, which has led to the development of a new world-wide industry providing lightweight, affordable metallic castings for applications ranging from aerospace, to sporting goods, to consumer electronics.     

The 2007 Benjamin Franklin medal in electrical engineering presented to Robert H. Dennard, Ph.D.

For inventing the 1-transistor/1-capacitor dynamic random access memory that significantly reduced the cost of memory, and for contributing to the development of the metal oxide semiconductor scaling principle that guides the design of increasingly small and complex integrated circuits.     

MicroRNAs: Potential biomarkers in cancer

microRNAs (miRNAs) are evolutionarily conserved small noncoding RNAs, also known as micromanagers of gene expression. Polymorphisms in the miRNA pathway (miR-polymorphisms) are emerging as powerful tools to study the biology of a disease and have the potential to be used in disease prognosis and diagnosis. Advancements in the miRNA field also indicate a clear involvement of deregulated miRNA gene signatures in cancers, and several polymorphisms in pre-miRNA, miRNA binding sites or targets have been found to be associated with various cancers. The miRNA polymorphisms have also been reported to influence tumor aggressiveness as well as survival of cancer patients. miRNAs have a revolutionary impact on cancer research over recent years. They emerge as important players in tumorigenesis, leading to a paradigm shift in oncology. The extensive and comprehensive use of miRNA microarrays has enabled the identification of a number of miRNAs as potential biomarkers for cancer. Many miRNAs have been identified to act as oncogenes, tumor suppressors, or even modulators of cancer stem cells and metastasis. Some studies not only reported the identified miRNA biomarkers, but also deciphered their target genes and the underlying mechanisms. The rapid discovery of many miRNA targets and their relevant pathways has contributed to the development of miRNA-based therapeutics.     

Local peer communities and future academic success of Ph.D. candidates

Compared to senior scientists, early-career scientists have largely been neglected in the literature on academic success. This study aims to identify the effects of local peer communities of Ph.D. candidates on their future careers. We argue that local communities of Ph.D. candidates may offer both supportive and competitive environments depending on the nature of the relationships between its members. While Ph.D. candidates generally learn from and support each other in their local peer communities, they may also compete for their mentor's attention and future academic positions. We analyse such complex peer effects for 90,264 Ph.D. candidates in the field of mathematics in a genealogical way, by measuring a candidate's academic career success by the number of next-generation Ph.D. candidates supervised later on. To capture both the supportive and competitive peer effects, we distinguish between local peers who share mentors (co-mentees) and other local peers. Our result suggests that competition exists primarily among peers who share mentors, and only at the start of one's career. We also find supportive effects among peers who do not share mentors, particularly those from the same cohort. Our results highlight the importance of universities supporting informal interactions among Ph.D. candidates.     

基于生命周期的电子资源管理工作实践及探讨——以福建医科大学图书馆为例

[目的/意义]旨在探索如何科学合理、有效、规范化地管理电子资源。[方法/过程]通过分析电子资源在其生命周期(发现、试用、选择、采购、管理、评估)工作流程中不同的任务和工作内容,发现在日常维护、使用评估、验收管理等方面问题,进行管理工作上实践性的总结。[结果/结论]构建科学合理的电子资源管理体系可从建立电子资源管理制度、引进或开发电子资源管理系统,以及加强电子资源专业馆员队伍建设等多方面着手,使电子资源管理工作朝着生态化、可持续发展的方向发展。     

The 2010 Benjamin Franklin Medal in Life Science presented to Peter C. Nowell

Peter Nowell is known for his discovery that a small terminal deletion on chromosome 22 is a consistent feature in leukemic cells from chronic myelogenous leukemia (CML) patients. This was the first direct evidence that a human cancer could be the result of a somatic (chromosomal) mutation, and paved the way for the development of a therapy that now cures 95% of individuals with CML.     

Functional requirement of terminal inverted repeats for efficient ProtoRAG activity reveals the early evolution of V(D)J recombination

The discovery of ProtoRAG in amphioxus indicated that vertebrate RAG recombinases originated from an ancient transposon. However, the sequences of ProtoRAG terminal inverted repeats (TIRs) were obviously dissimilar to the consensus sequence of mouse 12/23RSS and recombination mediated by ProtoRAG or RAG made them incompatible with each other. Thus, it is difficult to determine whether or how 12/23RSS persisted in the vertebrate RAG system that evolved from the TIRs of ancient RAG transposons. Here, we found that the activity of ProtoRAG is highly dependent on its asymmetric 5′TIR and 3′TIR, which are composed of conserved TR1 and TR5 elements and a partially conserved TRsp element of 27/31 bp to separate them. Similar to the requirements for the recombination signal sequences (RSSs) of RAG recombinase, the first CAC in TR1, the three dinucleotides in TR5 and the specific length of the partially conserved TRsp are important for the efficient recombination activity of ProtoRAG. In addition, the homologous sequences flanking the signal sequences facilitate ProtoRAG- but not RAG-mediated recombination. In addition to the diverged TIRs, two differentiated functional domains in BbRAG1L were defined to coordinate with the divergence between TIRs and RSSs. One of these is the CTT* domain, which facilitates the specific TIR recognition of the BbRAGL complex, and the other is NBD*, which is responsible for DNA binding and the protein stabilization of the BbRAGL complex. Thus, our findings reveal that the functional requirement for ProtoRAG TIRs is similar to that for RSS in RAG-mediated recombination, which not only supports the common origin of ProtoRAG TIRs and RSSs from the asymmetric TIRs of ancient RAG transposons, but also reveals the development of RAG and RAG-like machineries during chordate evolution.     

Ferroelectric liquid crystals: The 2004 Benjamin Franklin Medal in Physics presented to Robert B. Meyer of Brandeis University

In a theoretical examination of the structures of liquid crystal phases, Robert B. Meyer in 1975 creatively utilized symmetry arguments to predict that tilted, layered liquid crystal phases of chiral molecules are ferroelectric. He then engaged the help of organic chemists to synthesize a compound that might possess such a phase, and once the material was in his hands, Meyer not only verified its ferroelectricity, but also suggested how such a phase could be used for extremely fast displays. This discovery of ferroelectricity in a fluid system with the possibility for unique applications surprised the entire condensed matter research community and quickly paved the way for both increased scientific understanding and significant technological advancement. For this creative synthesis of theory and experiment, Meyer was awarded the 2004 Benjamin Franklin Medal in Physics.     

Medical knowledge discovery systems: data abstraction and performance measurement

Knowledge discovery systems can be traced back to their origin, artificial intelligence and expert systems, but use the modern technique of data mining for the knowledge discovery process. To that end, the technical community views data mining as one step in the knowledge discovery process, while the non-technical community seems to view it as encompassing all of the steps to knowledge discovery. In this exploratory study, we look at medical knowledge discovery systems (MKDSs) by first looking at three examples of expert systems to generate medical knowledge. We then expand on the use of data abstraction as a pre-processing step in the comprehensive task of medical knowledge discovery. Next, we look at how performance of a medical knowledge discovery system is measured. Finally, the conclusions point to a bright future for MKDSs, but an area that needs extensive development to reach its full potential.     

Intellectual property rights,non-market considerations and foreign R&D investments

Prior research has focused on how firms use a variety of organizational mechanisms to protect their R&D investments from misappropriation risks in foreign countries. Little is known, however, about how firms can rely on non-market factors to induce preferential treatment by host government authorities, thereby protecting their intellectual property overseas. In this paper, we investigate two such non-market factors, one at the country level, the other at the firm level, that are likely to influence the choice of where firms locate their innovation activities: host country inclination towards the firm's home country and the firm's political capabilities, respectively. We thus examine how IPR policies and non-market factors interact in protecting firm innovation from misappropriation and in making countries more attractive for innovation-related activities. We find support for our predictions in a sample of 1,341 foreign R&D investments made by 163 firms from 14 home countries over the period 2003–2016.     

植物非编码RNA与抗虫防御反应的研究及应用

非编码RNA参与了多种重要的生命进程,是当今研究的热点领域。在植物中,非编码RNA除了参与维持基因组的稳定,还在生长、发育、逆境胁迫反应等过程中发挥重要作用。RNA干扰(RNA interference,RNAi)是指由RNA触发的相应基因的表达抑制,是非编码RNA调控基因表达的一种重要的作用方式,自发现以来已逐渐发展为遗传分析、疾病治疗以及植物保护等方面的有效的新技术。文章重点介绍了微RNA(micro RNA,mi RNA)在植物抗虫防御中的生物学功能,si RNA对植物防御记忆的影响以及RNAi对植物防御信号途径的调节作用,同时阐述了RNAi在提高农作物抗虫性上的应用并展望了未来植物非编码RNA的研究方向。     

Free DNA – new potential analyte in clinical laboratory diagnostics?

The existence of cell free DNA in the human circulatory system has been known since the 1950s, however, intensive research in this area has been conducted for the last ten years. This review paper brings a short overview of the existing literature concerning the cell free DNA research in various clinical fields and pathological states and considers the application possibilities of this new analyte in clinical laboratory diagnostics. At the moment, cell free DNA is most widely used for the purpose of non-invasive prenatal diagnosis of fetal sex or fetal RhD status. The recent discovery of epigenetic changes in placental/fetal DNA and the detection of fetal/placental-specific RNAs have made it possible to use this technology in all pregnancies irrespective of the gender of the fetus. With the application of new techniques such as next generation sequencing, digital PCR and mass spectrometry, it is now possible to detect very small amounts of specific DNA in the presence of excess of other nonspecific nucleic acids. Second most probable application is in oncology, where detection and monitoring of tumors is now possible by the detection of tumor-derived nucleic acids. Third promising field for near future implementation of this analyte is transplantation medicine, where free DNA level could serve as a marker of transplant rejection. Before any further utilization of this new biomarker, pre-analytical and analytical aspects of free DNA analysis remain to be standardized. In the field of noninvasive prenatal diagnosis, important ethical, legal and social questions remain to be discussed.     

探讨发现法在高中历史教学中的应用

探讨发现法作为帮助学生理解历史的一种教学策略,它有助于引导、启发学生的发散思维,培养学生的创新能力、协助学生理解知识障碍,提高学生解题和解决实际问题的能力。本文从课堂教学的三个阶段探讨如何实施该方法提高教学效果和学生思维能力,从而培养学生主动学习,提高高中历史课堂效率。     

西藏菊科植物

 1)  The Compositae in Tibet so far known comprise 508 species and 88 genera, which nearly amounts to one fourth of the total number of genera and one third of the total number of species of Compositae in all China, if the number of 2290 species and 220 genera have respectively been counted in all China. In Tibet there are all tribes of Com- positae known in China, and surprisingly, the large tribes in Tibetan Compositae are also large ones in all China and the small tribes in Tibet are also small ones in all China. Generally speaking, the large genera in Tibet are also large ones in all China and the small genera in Tibet are likewise small ones in all China. In this sense it is reasonable to say that the Compositae flora of Tibet is an epitome of the Compositae flora of all China.      In the Compositae flora of Tibet, there are only 5 large genera each containing 30 species or more. They are Aster, Artemisia, Senecio, Saussurea and Cremanthodium. And 5 genera each containing 10—29 species. They are Erigeron, Anaphalis, Leontopodium, Ajania, Ligularia and Taraxacum. In addition, there are 77 small genera, namely 87% of the total of Compositae genera in Tibet, each comprising 1—9 species, such as Aja-niopsis, Cavea and Vernonia, etc.      2)  The constituents of Compositae flora in Tibet is very closely related to those of Sichuan-Yunnan provinces with 59 genera and 250 species in common. Such a situation is evidently brought about by the geographycal proximity in which the Hengtuang Shan Range links southeastern and eastern Tibet with northern and northwestern Sichuan- Ynnnan.  With India the Tibetan Compositae have 59 genera and 132 species in common, also showing close floristic relationships between the two regions. Apparently the floris- tic exchange of Compositae between Tibet and India is realized by way of the mountain range of the Himalayas.  The mountain range of the Himalayas, including the parallel ranges, plays a important role as a bridge hereby some members of the Compositae of western or northern Central Asia and of the northern Africa or of western Asia have migrated eastwards or southeastwards as far as the southern part of Fibet and northern part of India, or hereby some Compositae plants of eastern and southeastern Asia or Asia Media have migrated northwestwards as the northern part of Central Asia.      Some of the species and genera in common to both Tibet and Sinjiang indicate that this weak floristical relationship between these regions is principally realized through two migration routes: one migration route is by way of the Himalayas including the parallel ranges to Pamir Plataeu and Tien Shan, or vice versa. The other migration route is by way of northern Sinjiang to Mongolia, eastern Inner Mongolia, southwards to Gansu, Qinghai (or western Sichuan), eastern Tibet up to the Himalayas, or vice versa.      However, Tibet is not entirely situated at a migration crossroad of the floral ele- ments. An ample amount of the data shows that Compositae flora have a particular capability of development in Tibet. of the total number of species of Tibetan Com- positae, 102 species and 1 genus (Ajaniopsis Shih) are endemic. Besides, 8 genera are re- gional endemics with their range extending to its neighbourhood. The higher percentage of endemics at specific level than at generic in Tibetan Compositae may be a result of active speciation in response to the new enviromental conditions created by the uplifting of the Himalayas.  The flora in Tibetan Plateau as a whole appears to be of a younger age.       3) The uprising of the Himalayas and of the Tibetan Plateau accompanied by the ultraviolet ray radiation, the microthermal climate and the high wind pressure has, no doubt, played a profound influence upon the speciation of the native elements of Tibetan Compositae. The recent speciation is the main trend in the development of the Com-positae flora native in Tibet in the wake of upheaval of the plateau.     

Edward B. Aveling: the people's Darwin

By the late-19th century, evolutionary theory, known by most people as Darwinism, had earned a reputation as an atheistic theory that challenged religious orthodoxy. From recent historical work we now know a great deal about how those with religious convictions received Darwinian ideas, and the role that professional scientists played in styling and communicating 'Darwinism' to the wider public and between themselves. However, relatively little is known about how Darwinian ideas were received and used by avowedly irreligious groups, and how these groups set about communicating their own version of Darwinism to a public hungry for cheap and accessible science. The activities of the Secularist Edward Bibbins Aveling, a prolific popularizer of Darwinian ideas in the late-19th century, offer a unique insight into this relatively uncharted territory. His work helped to develop the polemic of popular irreligious groups and imbue Darwinism with overtly atheistic connotations; it also engendered unprecedented support for atheism from the general public, and challenged the monopoly that some professional scientists enjoyed over imparting serious scientific knowledge to them.