Knowing what would happen: The epistemic strategies in Galileo's thought experiments

While philosophers have subjected Galileo's classic thought experiments to critical analysis, they have tended to largely ignored the historical and intellectual context in which they were deployed, and the specific role they played in Galileo's overall vision of science. In this paper I investigate Galileo's use of thought experiments, by focusing on the epistemic and rhetorical strategies that he employed in attempting to answer the question of how one can know what would happen in an imaginary scenario. Here I argue we can find three different answers to this question in Galileo later dialogues, which reflect the changing meanings of ‘experience’ and ‘knowledge’ (scientia) in the early modern period. Once we recognise that Galileo's thought experiments sometimes drew on the power of memory and the explicit appeal to ‘common experience’, while at other times, they took the form of demonstrative arguments intended to have the status of necessary truths; and on still other occasions, they were extrapolations, or probable guesses, drawn from a carefully planned series of controlled experiments, it becomes evident that no single account of the epistemological relationship between thought experiment, experience and experiment can adequately capture the epistemic variety we find Galileo's use of imaginary scenarios. To this extent, we cannot neatly classify Galileo's use of thought experiments as either ‘medieval’ or ‘early modern’, but we should see them as indicative of the complex epistemological transformations of the early seventeenth century.     

Of the morphogenes that make a ring, a rod and a sphere in Escherichia coli

In 1993, William Donachie wrote "The success of molecular genetics in the study of bacterial cell division has been so great that we find ourselves, armed with much greater knowledge of detail, confronted once again with the same naive questions that we set to answer in the first place". Indeed, attempts to answer the apparently simple question of how a bacterial cell divides have led to a wealth of new knowledge, in particular over the past decade and a half. And while some questions have been answered to a great extent since the early reports of isolation of division mutants of Escherichia coli, some key pieces of the puzzle remain elusive. In addition to it being a fundamental process in bacteria that merits investigation in its own right, studying the process of cell division offers an abundance of new targets for the development of new antibacterial compounds that act directly against key division proteins and other components of the cytoskeleton, which are encoded by the morphogenes of E. coli. This review aims to present the reader with a snapshot summary of the key players in E. coli morphogenesis with emphasis on cell division and the rod to sphere transition.     

The role of orientation experiments in discovering mechanisms

Many types of experiments have been recognized in the literature. One important type we discuss in this article is the orientation experiment. While orientation experiments are like other types of experiments in that they are tests for causal relevance, they also have other qualities. One important (but not the only) goal of these experiments is to offer a rough, qualitative characterization of the mechanism responsible for a capacity of interest, effectively constraining future research. This makes them particularly useful during the early stages of investigation, when an explanandum-phenomenon has just been identified and several (often competing) hypotheses as to the qualitative character of the mechanism responsible for it are proposed. We illustrate our claims, and explicate a number of additional aims that orientation experiments can sometimes serve, by considering three case studies from different era's, namely the discovery of the mechanisms responsible for i) the capacity of eels to produce numbing sensations (17th and 18th century), ii) puerperal fever in Semmelweis' Vienna Maternity Hospital (19th century), and iii) the capacity of pigeons to home (20th century).     

A quantitative difference in the immune response to sheep red cells between rat strains

Résumé Des rats appartenant à plusieurs souches ont été immunisés par injection i.p. de 2×10⁸ globules rouges de mouton. La mesure du titre des haemolysines réalisée 6 jours plus tard montre des différences quantitatives selon les souches. Une réponse importante n'a pu être décelée que pour 3 d'entre elles (August, OFA et Wistar R).     

Inhibition of the primary immune response against sheep red blood cells by short-term reticulo-endothelial system blockage experiments in mice

Zusammenfassung Mäuse wurden gegen Schaferythrozyten immunisiert und die Immunreaktion im Plaque-Test von Jerne gemessen. Erhalten die Tiere unmittelbar vor der Antigeninjektion Thorotrast, so kommt es zur statistisch hochsignifikanten Hemmung der Antikörper bildenden Zellen.     

Language understanding is grounded in experiential simulations: a response to Weiskopf

Several disciplines within the cognitive sciences have advanced the idea that people comprehend the actions of others, including the linguistic meanings they communicate, through embodied simulations where they imaginatively recreate the actions they observe or hear about. This claim has important consequences for theories of mind and meaning, such as that people’s use and interpretation of language emerges as a kind of bodily activity that is an essential part of ordinary cognition. Daniel Weiskopf presents several arguments against the idea that experiential simulations play a major role in immediate language use and meaning. We offer several rebuttals to Weiskopf, in which we critique his interpretation of simulation theory, present additional psycholinguistic evidence supportive of the simulation perspective, and suggest that a more traditional theory of linguistic meaning and processing has little psychological and empirical validity.     

EGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy

Glioblastoma is a particularly resilient cancer, and while therapies may be able to reach the brain by crossing the blood–brain barrier, they then have to deal with a highly invasive tumor that is very resistant to DNA damage. It seems clear that in order to kill aggressive glioma cells more efficiently and with fewer side effects on normal tissue, there must be a shift from classical cytotoxic chemotherapy to more targeted therapies. Since the epidermal growth factor receptor (EGFR) is altered in almost 50 % of glioblastomas, it currently represents one of the most promising therapeutic targets. In fact, it has been associated with several distinct steps in tumorigenesis, from tumor initiation to tumor growth and survival, and also with the regulation of cell migration and angiogenesis. However, inhibitors of the EGFR kinase have produced poor results with this type of cancer in clinical trials, with no clear explanation for the tumor resistance observed. Here we will review what we know about the expression and function of EGFR in cancer and in particular in gliomas. We will also evaluate which are the possible molecular and cellular escape mechanisms. As a result, we hope that this review will help improve the design of future EGFR-targeted therapies for glioblastomas.     

Some new aspects of a sheep pineal gonadotropic inhibiting activity in in vitro experiments

Résumé Par des méthodes simples et bien déterminées: gelfiltration sur Sephadex G-25, G-10 et l'ultrafiltration par des diaflomembranes UM-02 et UM-05, on a pu isoler à partir d'un extrait aqueux d'épiphyses de mouton, des fractions capables d'inhiber l'activité gonadotrope hypophysaire. Cette activité inhibitrice a pu être localisée par l'électrophorèse sur papier. Les fractions ainsi obtenues sont capables d'inhiber in vitro l'excrétion hypophysaire de FSH et de LH.

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Acknowledgment. The authors gratefully acknowledge Dr. Reichert and Dr. Niswender for the generous supply of antigens and antibodies for the radioimmunoassay. Our thanks are also due to Mrs. A. E. M. Horwitz-Bresser for her skilful assistance in the isolation procedures.     

Glutamate decarboxylase activity in brain regions of differentially-housed mice; a difference in the olfactory bulb

Summary Glutamate decarboxylase (GAD) activities were determined in homogenates of 8 brain regions of mice that had been differentially housed (isolated vs grouped) for 4–9 weeks. GAD activity was lower in whole forebrains and in olfactory bulbs of isolated mice, changes which might be associated with their increased aggressiveness.     

Evidence that prokineticin receptor 2 exists as a dimer in vivo

Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2. In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2 has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains. Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can re-establish receptor functionality, possibly through a domain-swapping mechanism.     

Cone mosaic in a teleost retina: No difference between light and dark adapted states

Summary The mosaic arrangement of retinal cones in the eye of the African cichlid fish,Haplochromis burtoni, is the same in both light and dark adapted states. This is in contrast to Kunz' claim² that the retinal mosaic pattern changes from a square to a row type during dark adaptation, in the guppy (Poecelia reticulata). Kunz' histological procedure may account for this difference in results.Acknowledgments. This work was supported by grants from the Whitehall Foundation and NIH EY02284. I thank L. Shelton for expert histological assistance.     

Nature in the laboratory — nature as a laboratory. Considerations about the ethics of release experiments

Field tests with genetically modified organisms go beyond the boundaries of the politically and morally neutralized space that normally surrounds scientific experiments. They enter public areas. As a social process of shaping nature they are political in a fundamental sense. Consequences of this observation concern the legitimacy of decisions and the legitimacy of deciding procedures. The political rights of citizens and their human rights can only be respected if these procedures are democratic. Without a more serious exploration of the specific circumstances of release tests — for example, the precise ecological context, the consequences for the future development of the affected ecosystem, the social consequences, and the possible institutional ways of establishing gene technology in agriculture — we do not really know what we are doing when we release transgenic organisms. Moral judgements today can therefore only be prima facie, not free from shortcomings. As responsible judges we must confess that we are still morally blind.     

Intracellular free calcium as a pathogen in cell damage initiated by the immune system

Summary It is proposed that the earliest intracellular event induced by the action of complement is an increase in cytosolic free calcium, which can occur in the absence of lysis. This increase causes morphological and chemical changes in the cell and also results in modified responses to physiological stimuli.In this article the term free calcium is used to mean ionised calcium, i.e. Ca²⁺, not bound to ligands.Acknowledgments. We are grateful to members of the Welsh National School of Medicine, University of Cambridge, School of Clinical Medicine, and the Marine Biological Association Laboratory, Plymouth, for valuable advice and discussions. In particular we thank our colleagues Dr M.B. Hallett, Dr P.J. Richardson and Mr R.A. Daw. We thank the Science and Medical Research Councils, the British Diabetic Association and the Arthritis and Rheumatism Council for supporting our experimental work.