The role of meta-empirical theory assessment in the acceptance of atomism

The universal acceptance of atomism in physics and chemistry in the early 20th century went along with an altered view on the epistemic status of microphysical conjectures. Contrary to the prevalent understanding during the 19th century, on the new view unobservable objects could be ‘discovered’. It is argued in the present paper that this shift can be connected to the implicit integration of elements of meta-empirical theory assessment into the concept of theory confirmation.     

The role of a posteriori mathematics in physics

The calculus that co-evolved with classical mechanics relied on definitions of functions and differentials that accommodated physical intuitions. In the early nineteenth century mathematicians began the rigorous reformulation of calculus and eventually succeeded in putting almost all of mathematics on a set-theoretic foundation. Physicists traditionally ignore this rigorous mathematics. Physicists often rely on a posteriori math, a practice of using physical considerations to determine mathematical formulations. This is illustrated by examples from classical and quantum physics. A justification of such practice stems from a consideration of the role of phenomenological theories in classical physics and effective theories in contemporary physics. This relates to the larger question of how physical theories should be interpreted.     

History and scientific practice in the construction of an adequate philosophy of science: revisiting a Whewell/Mill debate

William Whewell raised a series of objections concerning John Stuart Mill’s philosophy of science which suggested that Mill’s views were not properly informed by the history of science or by adequate reflection on scientific practices. The aim of this paper is to revisit and evaluate this incisive Whewellian criticism of Mill’s views by assessing Mill’s account of Michael Faraday’s discovery of electrical induction. The historical evidence demonstrates that Mill’s reconstruction is an inadequate reconstruction of this historical episode and the scientific practices Faraday employed. But a study of Faraday’s research also raises some questions about Whewell’s characterization of this discovery. Thus, this example provides an opportunity to reconsider the debate between Whewell and Mill concerning the role of the sciences in the development of an adequate philosophy of scientific methodology.     

Recent insights into the role of integrins in cancer metastasis

Integrins have been repeatedly found involved in cancer metastasis. The past two years have seen considerable evolution in our knowledge on the role of these integrins in tumour cells. This includes the elucidation of different signalling pathways by which integrins dictate the anchorage-independent growth, survival and motility of tumour cells. Moreover, integrins may have a more complex role in cancer metastasis as they cooperate with serine proteases and metalloproteases to promote tumour cell invasion and angiogenesis. Finally, integrins favour tumor cell extravasation.     

Making the abstract concrete: The role of norms and values in experimental modeling

Experimental modeling is the construction of theoretical models hand in hand with experimental activity. As explained in Section 1, experimental modeling starts with claims about phenomena that use abstract concepts, concepts whose conditions of realization are not yet specified; and it ends with a concrete model of the phenomenon, a model that can be tested against data. This paper argues that this process from abstract concepts to concrete models involves judgments of relevance, which are irreducibly normative. In Section 2, we show, on the basis of several case studies, how these judgments contribute to the determination of the conditions of realization of the abstract concepts and, at the same time, of the quantities that characterize the phenomenon under study. Then, in Section 3, we compare this view on modeling with other approaches that also have acknowledged the role of relevance judgments in science. To conclude, in Section 4, we discuss the possibility of a plurality of relevance judgments and introduce a distinction between locally and generally relevant factors.     

Measuring the probability of a business cycle turning point by using a multivariate qualitative hidden Markov model

A two‐step procedure to produce a statistical measure of the probability of being in an accelerating or decelerating phase of economic activity is proposed. It consists of, first, an extraction of the individual linear innovations of a set of relevant macroeconomic variables whose signs are accumulated into a qualitative vector process and, second, of a factor analysis applied to this vector. The factor process is a two‐state Markov process of order one whose states are described as favourable and unfavourable. Estimated on French business surveys, this measure appears to be a competitive coincident indicator. Copyright © 2000 John Wiley & Sons, Ltd.     

Progesterone regulation of implantation-related genes: new insights into the role of oestrogen

Genomic profiling was performed on explants of late proliferative phase human endometrium after 24-h treatment with progesterone (P) or oestradiol and progesterone (17β-E₂+P) and on explants of menstrual phase endometrium treated with 17β-E₂+P. Gene expression was validated with real-time PCR in the samples used for the arrays, in endometrium collected from early and mid-secretory phase endometrium, and in additional experiments performed on new samples collected in the menstrual and late proliferative phase. The results show that late proliferative phase human endometrium is more responsive to progestins than menstrual phase endometrium, that the expression of several genes associated with embryo implantation (i.e. thrombomodulin, monoamine oxidase A, SPARC-like 1) can be induced by P in vitro, and that genes that are fully dependent on the continuous presence of 17β-E₂ during P exposure can be distinguished from those that are P-dependent to a lesser extent. Therefore, 17β-E₂ selectively primes implantation-related genes for the effects of P. H. Dassen, C. Punyadeera: These authors contributed equally. Received 18 December 2006; received after revision 6 February 2007; accepted 8 March 2007     

The concept of transition and its role in Leibniz’s and Whitehead’s metaphysics of motion

Leibniz’s and Whitehead’s analyses of motion are at the heart of their metaphysical schemes. These schemes are to be considered as two blueprints of a similar metaphysical intuition that emerged during two breakthrough eras, that is, the 17th century and the beginning of the 20th century, and retained the Aristotelian idea that existence requires an active principle. The two philosophers’ attempts to elucidate this idea in the context of their analyses of motion still interact with central, longstanding questions in philosophy, in particular that concerning the ontological status of change. For both thinkers, the phenomenon of motion is an example par excellence, of the metaphysically fundamental principle of action that is required for change in the world. I focus on Leibniz’s and Whitehead’s similar understanding of the concept of transition that is inserted as an essential constitutive component of motion and ensures its status as something real.     

Endogenous synthesis of peptidoglycan in eukaryotic cells; a novel concept involving its essential role in cell division,tumor formation and the biological clock

Degradation products of peptidoglycan, the universal bacterial cell wall constituent, were previously found in animal tissues and urine. Reassessment and quantitative analysis of available data lead to an original concept, i.e. that eukaryotic cells synthesize peptidoglycan. We present a model in which this endogenously synthesized peptidoglycan is essential for the processes of eukaryotic cell division and sleep induction in animals. Genes for peptidoglycan metabolism, like those for lysine biosynthesis in plants, are probably inherited from endosymbiotic bacteria, the ancestors of mitochondria and chloroplasts. Corollaries of this concept, i.e. roles for peptidoglycan metabolism in tumor formation and in the biological clock, are supported by abundant evidence. We propose that many interactions between bacteria and eukaryotes are conditioned by their common genetic heritage.     

Endogenous synthesis of peptidoglycan in eukaryotic cells; a novel concept involving its essential role in cell division, tumor formation and the biological clock.

Degradation products of peptidoglycan, the universal bacterial cell wall constituent, were previously found in animal tissues and urine. Reassessment and quantitative analysis of available data lead to an original concept, i.e. that eukaryotic cells synthesize peptidoglycan. We present a model in which this endogenously synthesized peptidoglycan is essential for the processes of eukaryotic cell division and sleep induction in animals. Genes for peptidoglycan metabolism, like those for lysine biosynthesis in plants, are probably inherited from endosymbiotic bacteria, the ancestors of mitochondria and chloroplasts. Corollaries of this concept, i.e. roles for peptidoglycan metabolism in tumor formation and in the biological clock, are supported by abundant evidence. We propose that many interactions between bacteria and eukaryotes are conditioned by their common genetic heritage.     

Expansion of amino acid homo-sequences in proteins: Insights into the role of amino acid homo-polymers and of the protein context in aggregation

Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines, in proteins has been directly implicated in various degenerative diseases through a mechanism of protein misfolding and aggregation. However, it is still unclear how the nature of the expansion and the protein context influence the tendency of a protein to aggregate. Here, we have addressed these questions using spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the polyglutamine proteins, chosen as a model system. Using a transfected mammalian cell line, we demonstrate that ATX3 aggregation is noticeably reduced by deletion or replacement of regions other than the polyglutamine tract. The nature of the amino acid homo-sequences also has a strong influence on aggregation. From our studies, we draw general conclusions on the effect of the protein architecture and of the amino acid homo-sequence on pathology. Received 3 March 2006; received after revision 19 April 2006; accepted 22 May 2006     

Current insights into the role of PKA phosphorylation in CFTR channel activity and the pharmacological rescue of cystic fibrosis disease-causing mutants

Cystic fibrosis transmembrane conductance regulator (CFTR) channel gating is predominantly regulated by protein kinase A (PKA)-dependent phosphorylation. In addition to regulating CFTR channel activity, PKA phosphorylation is also involved in enhancing CFTR trafficking and mediating conformational changes at the interdomain interfaces of the protein. The major cystic fibrosis (CF)-causing mutation is the deletion of phenylalanine at position 508 (F508del); it causes many defects that affect CFTR trafficking, stability, and gating at the cell surface. Due to the multiple roles of PKA phosphorylation, there is growing interest in targeting PKA-dependent signaling for rescuing the trafficking and functional defects of F508del-CFTR. This review will discuss the effects of PKA phosphorylation on wild-type CFTR, the consequences of CF mutations on PKA phosphorylation, and the development of therapies that target PKA-mediated signaling.     

A role for the hinge/ear domain of the β chains in the incorporation of AP complexes into clathrin-coated pits and coated vesicles

The clathrin-associated adaptor protein (AP) complexes drive the polymerization of clathrin in coated pits to form coated vesicles. It has previously been shown that the carboxyl-terminal hinge/ear domain of the β2 chain contains a binding site for clathrin and that removal of this domain from APs or from isolated β2 chains abrogates their ability to form clathrin coats in vitro. We show here that the hinge/ear domain is necessary for efficient incorporation of AP complexes into coated pits and coated vesicles in cells, a result that is consistent with the view that the β chains indeed provide an important interaction between the AP complexes and clathrin. Received 7 April 1997; received after revision 22 May 1997; accepted 28 May 1997     

物联网服务建模：一种基于环境建模的方法

物联网服务是传统Web服务通过传感器网络向物理环境的延伸,它通过传感器网络感知物理环境中的实体,也向物理环境实体施加作用.与传统Web服务相比,由于物联网服务受到所依赖的物理环境的时间受限性、资源受限性和设备潜在故障概率的影响,物联网服务的响应速度、服务能耗和容错能力等特性成为影响物联网系统整体特性的重要因素.因此,对物联网服务进行全面建模,对物联网服务所处的外部环境进行形式化描述,并结合物理环境模型对物联网服务的性质进行分析,对于确保物联网系统的正确性、稳定性非常必要.本文针对物联网服务的特点,结合基于环境建模的需求工程思想,提出一种基于环境的物联网服务三元问题域建模框架,给出了物联网服务建模本体以及相应的建模原则.在此基础上,提出了一种物联网服务行为建模方法,该方法将物联网服务和物理环境建模为概率时间自动机,将用户期望的服务特性描述为时序逻辑公式,为物联网服务功能行为正确性验证和非功能性约束可满足性验证奠定了基础.     

Boyle and the origins of modern chemistry: Newman tried in the fire

William Newman construes the Scientific Revolution as a change in matter theory, from a hylomorphic, Aristotelian to a corpuscular, mechanical one. He sees Robert Boyle as making a major contribution to that change by way of his corpuscular chemistry. In this article it is argued that it is seriously misleading to identify what was scientific about the Scientific Revolution in terms of a change in theories of the ultimate structure of matter. Boyle showed, especially in his pneumatics, how empirically accessible, intermediate causes, as opposed to ultimate, mechanical ones can be explored and identified by experiment. Newman is right to observe that Boyle constantly sought intimate links between chemistry and the mechanical philosophy. However, by doing so he did not thereby significantly aid the cause of attaining experimental knowledge of chemical phenomena and the support that Boyle’s chemistry provided for the mechanical philosophy was weaker than both Boyle and Newman imply. Boyle was intent on articulating and defending a strict, mechanical account of the ultimate structure of matter to be sure, but his contributions to the new experimental science in general, and chemistry in particular, are best seen as distinct from that endeavour.     

Experiment versus mechanical philosophy in the work of Robert Boyle: a reply to Anstey and Pyle

We can distinguish ‘mechanical’ in the strict sense of the mechanical philosophers from ‘mechanical’ in the common sense. My claim is that Boyle's experimental science owed nothing to, and offered no support for, the mechanical philosophy in the strict sense. The attempts by my critics to undermine my case involve their interpreting ‘mechanical’ in something like the common sense. I certainly accept that Boyle's experimental science was productively informed by mechanical analogies, where ‘mechanical’ is interpreted in a common sense. But this leaves my original claim untouched and, in the main, unchallenged.     

Viewing past science from the point of view of present science,thereby illuminating both: Philosophy versus experiment in the work of Robert Boyle

The seventeenth century witnessed the replacement of an Aristotelian worldview by a mechanical one. It also witnessed the beginnings of significant experimental enquiry. Alerted by the fact that the methods involved in the latter, but not in the former, resemble those employed in later science, I argue the historical case that the emergence of the mechanical worldview and the emergence of science were not closely related and that it was the latter that was to develop into science as we have come to know it. The details are explored in the context of the philosophical and experimental work of Robert Boyle and the relationship between them.