Medieval Representations of Change and Their Early Modern Application

The article investigates the role of symbolic means of knowledge representation in concept development using the historical example of medieval diagrams of change employed in early modern work on the motion of fall. The parallel cases of Galileo Galilei, Thomas Harriot, and René Descartes and Isaac Beeckman are discussed. It is argued that the similarities concerning the achievements as well as the shortcomings of their respective work on the motion of fall can to a large extent be attributed to their shared use of means of knowledge representation handed down from antiquity and the Middle Ages. While the interpretation of medieval diagrams was unproblematic in the scholastic context from which they arose, in the early modern context, which was characterized by the confluence of natural philosophy and practical mathematics, it became ambiguous. It was the early modern mathematicians’ work within this contradictory framework that brought about a new conceptualization of motion which, in particular, eventually led to an infinitesimal concept of velocity. In this process, the diagrams themselves remained largely unchanged and thus functioned as a catalyst for concept development.     

Lumping,testing, tuning: The invention of an artificial chemistry in atmospheric transport modeling

Since the late 1950s computer simulation has been used to investigate the transport of pollutants in the atmosphere. About 20 years later also the chemical transformation of atmospheric pollutants was included in computer models of photochemical smog formation. Due to limited knowledge of atmospheric chemistry and due to limited computer capacity, chemical processes in the atmosphere were modeled with the help of simplified chemical models. In these models chemical substances are lumped together forming artificial virtual compounds with virtual characteristics. The paper aims at studying the practices developed in chemical model building and the creation of confidence in these models. Core of the paper will be the analysis of the Urban Airshed Model (UAM) for the Los Angeles region, a pioneering development in the early 1970s. The construction of the UAM involved the “lumping” of chemical processes and extensive testing and tuning. These practices led to a consistent model representation, in which diverse pieces of information fitted and were mutually stabilized. The pragmatic achievement of consistency created confidence, even though empirical tests of the models remained ambiguous and problematic.     

Requirements for leukocyte transmigration via the transmembrane chemokine CX3CL1

The surface-expressed transmembrane CX3C chemokine ligand 1 (CX3CL1/fractalkine) induces firm adhesion of leukocytes expressing its receptor CX3CR1. After shedding by the disintegrins and metalloproteinases (ADAM) 10 and 17, CX3CL1 also acts as soluble leukocyte chemoattractant. Here, we demonstrate that transmembrane CX3CL1 expressed on both endothelial and epithelial cells induces leukocyte transmigration. To investigate the underlying mechanism, we generated CX3CR1 variants lacking the intracellular aspartate-arginine-tyrosine (DRY) motif or the intracellular C-terminus which led to a defect in intracellular calcium response and impaired ligand uptake, respectively. While both variants effectively mediated firm cell adhesion, they failed to induce transmigration and rather mediated retention of leukocytes on the CX3CL1-expressing cell layer. Targeting of ADAM10 led to increased adhesion but reduced transmigration in response to transmembrane CX3CL1, while transmigration towards soluble CX3CL1 was not affected. Thus, transmembrane CX3CL1 mediates leukocyte transmigration via the DRY motif and C-terminus of CX3CR1 and the activity of ADAM10.     

Vaspin inhibits kallikrein 7 by serpin mechanism

The molecular target of the adipokine vaspin (visceral adipose tissue-derived serpin; serpinA12) and its mode of action are unknown. Here, we provide the vaspin crystal structure and identify human kallikrein 7 (hK7) as a first protease target of vaspin inhibited by classical serpin mechanism with high specificity in vitro. We detect vaspin–hK7 complexes in human plasma and find co-expression of both proteins in murine pancreatic β-cells. We further demonstrate that hK7 cleaves human insulin in the A- and B-chain. Vaspin treatment of isolated pancreatic islets leads to increased insulin concentration in the media upon glucose stimulation without influencing insulin secretion. By application of vaspin and generated inactive mutants, we find the significantly improved glucose tolerance in C57BL/6NTac and db/db mice treated with recombinant vaspin fully dependent on the vaspin serpin activity and not related to vaspin-mediated changes in insulin sensitivity as determined by euglycemic-hyperinsulinemic clamp studies. Improved glucose metabolism could be mediated by increased insulin plasma concentrations 150 min after a glucose challenge in db/db mice, supporting the hypothesis that vaspin may inhibit insulin degradation by hK7 in the circulation. In conclusion, we demonstrate the inhibitory serpin nature and the first protease target of the adipose tissue-derived serpin vaspin, and our findings suggest hK7 inhibition by vaspin as an underlying physiological mechanism for its compensatory actions on obesity-induced insulin resistance.     

阿拉斯加棕熊

苍茫的天色将这片土地笼罩在灰白与翠绿交映的肃穆光辉中。连绵的细雨为树叶和草地镀上一层闪亮的薄膜,灌木丛亦显得无比清新。这是自然界清洗一新的日子。     

Fish-Farming and the Precautionary Principle: Context and Values in Environmental Science for Policy

The paper starts with the assumption that the Precautionary Principle (PP) is one of the most important elements of the concept of sustainability. It is noted that PP has entered international treaties and national law. PP is widely referred to as a central principle of environmental policy. However, the precise content of PP remains largely unclear. In particular it seems unclear how PP relates to science. In section 2 of the paper a general overview of some historical and systematic features of PP are presented. In section 3 a specific case is discussed in greater detail. It is claimed that the escape of farmed salmon from fish cages in the Sea, and its eventual invasion of the breeding places of the wild salmon up the rivers, must be regarded a proper case for applying PP. Yet there is no single PP-strategy. Instead, four different strategies are presented, and all of them can be regarded precautionary strategies in the light of PP. The choice between these strategies is based upon personal values. In section 4 of the paper a general analysis is given which relates these different value perspectives to basic differences in risk aversion, which in turn are related to differing conceptions of nature and/or society. In the concluding section 5 some general consequences of the foregoing analysis are outlined.     

A draft genome of Yersinia pestis from victims of the Black Death

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.