Biochemical polymorphism of Japanese quail (Coturnix coturnix japonica): comparison of functionally different proteins (author's transl)]

The polymorphism observed among the enzymes involved in the respiratory metabolism (lactate dehydrogenase, malate dehydrogenase, phosphoglucomutase, phosphohexoseisomerase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase fructose 1-6 diphosphate dehydrogenase) is less important than that of the enzymes physiologically less essential, such as the various esterases, the alkaline phosphatase, the alcohol dehydrogenase, and of the non-enzymatic proteins (ovalbumin, ovoglobulins, ovomucoid, conalbumin, transferrin, etc.).     

系统论视野下小流域生态补偿机制构建思路——以秋浦河为例

针对小流域生态补偿实践中存在的补偿标准偏低、静态、管理体制不健全、补偿方式单一等弊端,采用系统研究、文献分析、实证检验等方法,揭示了秋浦河流域生态补偿机制,包括流域协调与管理机制;生态补偿法律机制;多元补偿方式机制;政府主导,市场参与的多元融资机制;公众参与、监督机制;动态补偿机制;科学确定补偿标准机制。基于秋浦河上游生态服务主导效应因子价值、生态保护成本、发展机会成本,下游社会经济发展实际,2009年下游补偿上游金额为41448．0277。秋浦河流域生态补偿机制构建,有利于促进秋浦河流域上、下游协调发展与社会公平,可为我国小流域生态补偿构建与实践提供借鉴与参考。     

The Chemistry of the Universe: Historical Roots of Modern Cosmochemistry

During the second half of the twentieth century, the domain of geochemistry has greatly expanded and the field is today often seen as a branch of an extended chemistry of the Earth, called cosmochemistry. This paper is a historical introduction to cosmochemistry in which the wider cosmic aspects are surveyed up to about 1915, when nuclear physics changed the scene. These wider aspects or themes include, firstly, the attempts to determine the relative abundances of the elements, secondly, the extension of geochemistry to include physical geochemistry, thirdly, the study of meteorites and, fourthly, the spectroscopic study of the stars within the astrochemical tradition. Because of the lack of reliable data, a great deal of the protocosmochemistry described in the present paper was speculative. Nonetheless, by 1915 the contours of the cosmochemistry of the future were just visible and the developments here singled out can thus be seen as belonging to the prehistory of modern cosmochemistry.     

Differential diurnal variations of anandamide and 2-arachidonoyl-glycerol levels in rat brain

The endogenous ligands of cannabinoid receptors, also known as endocannabinoids, have been implicated in many physiological and pathological processes of the central nervous system. Here we show that the levels of the two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), in four areas of the rat brain, change dramatically between the light and dark phases of the day. While anandamide levels in the nucleus accumbens, pre-frontal cortex, striatum and hippocampus were significantly higher in the dark phase, the opposite was observed with 2-AG, whose levels were significantly higher during the light phase in all four regions. We found that the activity of the fatty acid amide hydrolase, which catalyzes the metabolism of anandamide, was significantly lower during the dark phase, thus providing a possible explaination for the increase in anandamide levels. However, the activities of monoacylglycerol lipase and diacylglycerol lipase, two of the possible enzymes catalyzing the degradation and biosynthesis of 2-AG, respectively, changed significantly only in the striatum. These data suggest that the levels of the two major endocannabinoids might be under the control of endogenous factors known to undergo diurnal variations, and underscore the different roles, suggested by previous studies, of anandamide and 2-AG in neurophysiological processes.Received 9 December 2003; received after revision 15 January 2004; accepted 20 January 2004     

Fred Neufeld and pneumococcal serotypes: foundations for the discovery of the transforming principle

During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today’s knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld’s contributions in this development, which have remained largely unknown.     

Melatonin,clock genes and mitochondria in sepsis

After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.     

Chemistry and Chemists at the London Institution 1807-1912

The London Institution, established in the City of London in 1807, was devoted, as its full title proclaimed, to the 'advancement of Literature and the Diffusion of Useful Knowledge'. With its extensive lecture programme, splendid reference library, reading rooms, laboratory and other amenities, it provided for its members a scientific and cultural centre, modelled on the highly successful and fashionable Royal Institution in London's West End. Among its scientific activities, chemistry long maintained a leading role, in terms of both the sheer volume and variety of its presentations, and the high standing of its lecturers; they included Faraday, Playfair, Hofmann, Roscoe, Odling, Norman Lockyer, Meldola, and Sir William Ramsay, as well as other visiting lecturers, specially selected for their ability to present their subject in an interesting and attractive fashion to a wider lay public. The laboratory of the Institution, although limited in size and facilities, was the scene of instruction in practical chemistry, and between 1863 and 1884 attained the reputation of a significant centre of chemical research during the successive tenure of the professorship in chemistry by J. A. Wanklyn and H. E. Armstrong. Their publications, appearing under the device 'From the Laboratory of the London Institution', were a frequent feature of the leading chemical periodicals. Thus, within its many-sided activities, the Institution promoted significantly the public appreciation of the function of chemistry, as a contributor both to pure knowledge, and to technical and economic progress. It achieved this in an environment of influential City merchants, manufacturers and financiers and doubtless led to beneficient, if unrecorded, consequences. It was only towards the close of the nineteenth century, when the universities had become increasingly concerned with the systematic study of the discipline, that chemistry lost its direct impact in the London Institution, but continued to maintain a presence within its cultural framework.     

噬菌体D29的免疫原性及安全性评价

目的对噬菌体D29的免疫原性及安全性进行评价。方法将BALB／C小鼠随机分为噬菌体D29滴鼻暴露组（剂量9×10^8PFU）、噬菌体D29皮下注射组（剂量9×10^8PFU）,phagebuffer滴鼻组、phagebuffer皮下注射组、生理盐水滴鼻组、生理盐水皮下注射组、空白对照组,每组动物第一周第一天、第三天暴露一次,以后每周第一天暴露一次,共暴露6周。观察暴露期间噬菌体中和抗体的动态变化、暴露6周后血清中IL-2、IL-4、IL-12、IFN-1、TNF-α和NO的含量及CD4／CD8比例变化,小鼠碳粒廓清率变化、在饲养过程中各组动物的进食量以及活动、体重、生存情况,以及暴露结束后解剖取得脏器作病理学比较。结果D29滴鼻暴露组在第7天即产生低效价的中和抗体,第14天抗体效价下降,第28天之后不能检测到中和抗体,D29皮下注射组中和抗体从第7天开始产生,第21天上升,之后趋于稳定,其余组均无中和抗体产生。各组小鼠血清中细胞因子、CIM／CD8比例、碳粒廓清率以及饲养过程中各组动物的进食量以及活动、体重、生存情况均无明显差异。病理学上各实验组脏器除脾脏外均有轻微充血、水肿表现。结论D29具有抗原特性,可刺激机体产生中和抗体,但不会对机体的安全产生威胁。     

Quantum dissidents: Research on the foundations of quantum theory circa 1970

This paper makes a collective biographical profile of a sample of physicists who were protagonists in the research on the foundations of quantum physics circa 1970. We study the cases of Zeh, Bell, Clauser, Shimony, Wigner, Rosenfeld, d’Espagnat, Selleri, and DeWitt, analyzing their training and early career, achievements, qualms with quantum mechanics, motivations for such research, professional obstacles, attitude towards the Copenhagen interpretation, and success and failures. Except for Rosenfeld, they were all dissidents, fighting against the dominant attitude among physicists at the time according to which foundational issues had already been solved by the founding fathers of the discipline. Theirs is a story of success as the foundations of quantum mechanics finally entered the physics mainstream despite the fact that their expectations of breaking down quantum mechanics were not fulfilled.     

Crustal layering, simplicity, and the oil industry: The alteration of an epistemic paradigm by a commercial environment

This paper proposes that the gradual alteration of the predominant epistemic paradigm in crustal seismology in the interwar period—namely, simplicity—came about because of the strong influence of a particular commercial environment, i.e. the oil industry. I begin by demonstrating the interwar predominance of Jeffreys’ ‘simplicity postulate’ and his probabilistic epistemology, highlighting the espousal by several seismologists (Bullen, Stoneley, Byerly), whose crustal models drew on mathematical idealisations. Next, I demonstrate that the renunciation of simplicity in the 1930s came about too quickly, and, above all, too heterodoxically to have been the result of new geological evidence. Rather, I argue, the paradigm shift among seismologists was a result of the significant rise in seismic exploration generated by the oil industry. Driven by market demands, American petroleum companies pioneered new technologies, organised research initiatives, and trained young geophysicists who, through the fusion of experimentalism and field experience, brought about fundamental progress in earthquake seismology. Remarkably, historians of science have almost entirely failed to recognise the interwar primacy of the simplicity paradigm as well as its subsequent renunciation. More importantly, they have failed to acknowledge the role the oil industry played in contributing to this renunciation and to the development of new paradigms in seismology.     

The ‘Darwin-Marx correspondence’: a correction and revision

The logical links between the Judaeo-Christian doctrine of creation and the practice of natural philosophy on the one hand, and the rejection of belief in demonic agency on the other, were made explicit in the seventeenth century by, among others, Balthasar Bekker (1634–98), whose ideas I argue to have been not without influence. In section 1, I present the accounts of three historians of the opposition to belief in witchcraft and of the decline of the witch-persecution, Hugh Trevor-Roper, Keith Thomas, and Brian Easlea. In section 2, I maintain that Bekker has been underestimated both by Trevor-Roper and by Easlea. In section 3, I investigate more generally some of the connections between the new natural philosophy and belief in supernatural interventions, cast doubt on the view that rejection of belief in witchcraft and the devil requires rejection of belief in creation, and thus supplement or qualify the accounts of Trevor-Roper, Thomas, and Easlea of why belief in witchcraft faded away.     

基于场景模型的嵌入式软件测试

结合嵌入式软件的实时性、与硬件紧密结合等特点，采用UML对系统建模，引入场景技术描述系统预期的执行流程，提出了基于二叉树场景模型的测试用例生成方法。改善了人工设计测试用例时易发生的纰漏，如遗漏或冗余的测试用例、工作量大、效率低等问题，缩短了软件的开发周期。     

The plague fighter: Wu Lien-teh and the beginning of the Chinese public health system

At the end of 1910, when the Qing dynasty was on the verge of collapse and the whole Chinese empire in a process of transformation, North Manchuria was devastated by a large pneumonic plague epidemic. The Russian and Japanese governments wanted to use the outbreak of the disease as a pretext to invade north-east China, making plague an issue of international politics. At this dramatic moment the empire relied on the skills of the young Chinese doctor Wu Lien-teh, the first Chinese medical graduate from Cambridge. Wu investigated the disease on the spot, chaired an international plague conference in Shenyang (Manchuria) in April 1911, and, later on, became the figurehead of fundamental public health reforms in Republican China. Highly ambitious, striving for personal fame and international renown for China, supported by an excellent network of personal connections, and equipped with a medical training considered the best in the world at the time, he launched on a startling career as one of China's key medical reformers and international representatives. His history is an example of the inseparable links between personal fate and historical events, and between the interests of scientists, medical men, politicians, and businessmen on the national and international stages.     

Putting the Indices into practice: censoring science in early modern Portugal

ABSTRACT

During the sixteenth and seventeenth centuries, the Inquisition was the institution most invested in the censorship of printed books in the Portuguese empire. Besides publishing the Indices of Forbidden Books, the Holy Office was also responsible for overseeing their implementation and ensuring their efficacy in preventing the importation, reading, and circulation of banned books. Overall, the sixteenth-century Indices condemned 785 authors and 1081 titles, including 52 authors and 85 titles of medicine, natural history, natural philosophy, astronomy, chronology, cosmography, astrology, and divinatory arts. By looking at the largest collection of early modern scientific books in Portugal, I will argue that a closer inspection of marginalia and ownership, and the establishment of a typology of expurgations is essential for the comprehension of the actual practices and the mechanisms of censorship. By examining the material evidence of censorship, in order to reconstruct expurgation practices, this paper reveals the processes and effectiveness of ecclesiastical control in the Portuguese Inquisition and highlights the differences between what inquisitors wrote in the Indices and what others put into practice.     

Critical appraisals of approaches for predictive designs in anticancer drugs

The present review provides a critical appraisal of the most important areas in cancer drug research and, ultimately, in clinical oncology and therapy, with emphasis on the elucidation of possible predictive designs for the development of new anticancer drugs. These assessments encompass the well-established anticancer drugs and congeners which have been employed over the years in clinical therapy, and the more recent exploratory agents still requiring further rigorous scrutiny in the clinical environment. These areas mainly include the bioreversible redox carriers, the boron neutron capture compounds, some new mitosis-interactive agents, cell cycle modifiers, biological-response mpdifiers, oncogene inhibitors, drug-antibody conjugates, cancer cell suppression and destruction agents, antiangiogenesis and antimetastasis agents, apoptosis-promoting agents, and gene therapy and vaccines.     

略论城郊开发的现状及其生态学原理

随着城市规模的逐渐扩大,人们对城郊的开发强度也越来越大。人类的活动使城郊地区的景观、环境等发生了巨大的变化。本文从农业、乡镇企业发展、旅游业、养殖加工业、设施建设等方面的现状出发,简略阐述了盲目、过度开发对城郊生态系统产生的危害。并从植物的生活型选择、耐受性定律、生态位原理、植物的他感作用、群落时空格局构建、边缘效应、演替作用、物质循环再生、生态效率以及生物操纵等多角度论述了城郊开发中可用于解决上述问题的生态学原理。     

The implication of neuronimmunoendocrine (NIE) modulatory network in the pathophysiologic process of Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder implicitly marked by the substantia nigra dopaminergic neuron degeneration and explicitly characterized by the motor and non-motor symptom complexes. Apart from the nigrostriatal dopamine depletion, the immune and endocrine study findings are also frequently reported, which, in fact, have helped to broaden the symptom spectrum and better explain the pathogenesis and progression of PD. Nevertheless, based on the neural, immune, and endocrine findings presented above, it is still difficult to fully recapitulate the pathophysiologic process of PD. Therefore, here, in this review, we have proposed the neuroimmunoendocrine (NIE) modulatory network in PD, aiming to achieve a more comprehensive interpretation of the pathogenesis and progression of this disease. As a matter of fact, in addition to the classical motor symptoms, NIE modulatory network can also underlie the non-motor symptoms such as gastrointestinal, neuropsychiatric, circadian rhythm, and sleep disorders in PD. Moreover, the dopamine (DA)–melatonin imbalance in the retino-diencephalic/mesencephalic-pineal axis also provides an alternative explanation for the motor complications in the process of DA replacement therapy. In conclusion, the NIE network can be expected to deepen our understanding and facilitate the multi-dimensional management and therapy of PD in future clinical practice.     

Pursuing frequency standards and control: the invention of quartz clock technologies

The quartz clock, the first to replace the pendulum as the time standard and later a ubiquitous and highly influential technology, originated in research on means for determining frequency for the needs of telecommunication and the interests of its users. This article shows that a few groups in the US, Britain, Italy and the Netherlands developed technologies that enabled the construction of the new clock in 1927–28. To coordinate complex and large communication networks, the monopolistic American Telephone and Telegraph Company, and national laboratories needed to determine and maintain a common ‘standard’ frequency measurement unit. Exploiting novel piezoelectric quartz methods and valve electronics techniques, researchers in these organizations constructed a new crystal-based frequency standard. To ensure its accuracy they compared it to an accepted absolute standard - an astronomical clock, constructing thereby the first quartz clock. Other groups, however, had different, though connected, technological aims, which originated from the diverse interests of the industrial, governmental and academic institutes to which they belonged, and for which they needed to measure, control and manipulate with frequencies of electric oscillations. The present article suggests a comparative examination of the research and development paths of these groups on their incentives, the technological and scientific resources they utilized, and the kind of research carried out in the various institutional settings.     

Multiple roles for the actin cytoskeleton during regulated exocytosis

Regulated exocytosis is the main mechanism utilized by specialized secretory cells to deliver molecules to the cell surface by virtue of membranous containers (i.e., secretory vesicles). The process involves a series of highly coordinated and sequential steps, which include the biogenesis of the vesicles, their delivery to the cell periphery, their fusion with the plasma membrane, and the release of their content into the extracellular space. Each of these steps is regulated by the actin cytoskeleton. In this review, we summarize the current knowledge regarding the involvement of actin and its associated molecules during each of the exocytic steps in vertebrates, and suggest that the overall role of the actin cytoskeleton during regulated exocytosis is linked to the architecture and the physiology of the secretory cells under examination. Specifically, in neurons, neuroendocrine, endocrine, and hematopoietic cells, which contain small secretory vesicles that undergo rapid exocytosis (on the order of milliseconds), the actin cytoskeleton plays a role in pre-fusion events, where it acts primarily as a functional barrier and facilitates docking. In exocrine and other secretory cells, which contain large secretory vesicles that undergo slow exocytosis (seconds to minutes), the actin cytoskeleton plays a role in post-fusion events, where it regulates the dynamics of the fusion pore, facilitates the integration of the vesicles into the plasma membrane, provides structural support, and promotes the expulsion of large cargo molecules.