History of the Lenz–Ising Model 1950–1965: from irrelevance to relevance

This is the second in a series of three papers that charts the history of the Lenz–Ising model (commonly called just the Ising model in the physics literature) in considerable detail, from its invention in the early 1920s to its recognition as an important tool in the study of phase transitions by the late 1960s. By focusing on the development in physicists’ perception of the model’s ability to yield physical insight—in contrast to the more technical perspective in previous historical accounts, for example, Brush (Rev Modern Phys 39: 883–893, 1967) and Hoddeson et al. (Out of the Crystal Maze. Chapters from the History of Solid-State Physics. Oxford University Press, New York, pp. 489–616, 1992)—the series aims to cover and explain in depth why this model went from relative obscurity to a prominent position in modern physics, and to examine the consequences of this change. In the present paper, which is self-contained, I deal with the development from the early 1950s to the 1960s and document that this period witnessed a major change in the perception of the model: In the 1950s it was not in the cards that the model was to become a pivotal tool of theoretical physics in the following decade. In fact, I show, based upon recollections and research papers, that many of the physicists in the 1950s interested in understanding phase transitions saw the model as irrelevant for this endeavor because it oversimplifies the nature of the microscopic constituents of the physical systems exhibiting phase transitions. However, one group, Cyril Domb’s in London, held a more positive view during this decade. To bring out the basis for their view, I analyze in detail their motivation and work. In the last part of the paper I document that the model was seen as much more physically relevant in the early 1960s and examine the development that led to this change in perception. I argue that the main factor behind the change was the realization of the surprising and striking agreement between aspects of the model, notably its critical behavior, and empirical features of the physical phenomena.     

Nanocarriers’ entry into the cell: relevance to drug delivery

Nanocarriers offer unique possibilities to overcome cellular barriers in order to improve the delivery of various drugs and drug candidates, including the promising therapeutic biomacromolecules (i.e., nucleic acids, proteins). There are various mechanisms of nanocarrier cell internalization that are dramatically influenced by nanoparticles’ physicochemical properties. Depending on the cellular uptake and intracellular trafficking, different pharmacological applications may be considered. This review will discuss these opportunities, starting with the phagocytosis pathway, which, being increasingly well characterized and understood, has allowed several successes in the treatment of certain cancers and infectious diseases. On the other hand, the non-phagocytic pathways encompass various complicated mechanisms, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis, which are more challenging to control for pharmaceutical drug delivery applications. Nevertheless, various strategies are being actively investigated in order to tailor nanocarriers able to deliver anticancer agents, nucleic acids, proteins and peptides for therapeutic applications by these non-phagocytic routes.     

A researcher’s guide to the galaxy of IRESs

The idea of internal initiation is frequently exploited to explain the peculiar translation properties or unusual features of some eukaryotic mRNAs. In this review, we summarize the methods and arguments most commonly used to address cases of translation governed by internal ribosome entry sites (IRESs). Frequent mistakes are revealed. We explain why “cap-independent” does not readily mean “IRES-dependent” and why the presence of a long and highly structured 5′ untranslated region (5′UTR) or translation under stress conditions cannot be regarded as an argument for appealing to internal initiation. We carefully describe the known pitfalls and limitations of the bicistronic assay and artefacts of some commercially available in vitro translation systems. We explain why plasmid DNA transfection should not be used in IRES studies and which control experiments are unavoidable if someone decides to use it anyway. Finally, we propose a workflow for the validation of IRES activity, including fast and simple experiments based on a single genetic construct with a sequence of interest.     

On the “negative utility” of Ernst Cassirer׳s philosophy of physics: An application to the EPR argument

This paper tries to reconstruct Ernst Cassirer's potential reception of the EPR argument, as exposed by Einstein in his letter to Cassirer of March 1937. It is shown that, in conformity with his transcendental epistemology taking the conditions of accessibility as constitutive of the quantum object, Cassirer would probably have rejected the argument. Indeed, Cassirer would probably not have subscribed to its separability/local causality presupposition (which goes against his interpretation of the quantum formalism as a self-sufficient condition constitutive of the quantum object, without any reliance on spatial intuition), nor to its completeness requirement (as his partial endorsement of Bohr's complementarity, and his rejection of the Kantian "idea of complete determination", illustrate). By rejecting both of its premises, Cassirer's philosophy of physics thus enables to escape the EPR dilemma, and exhibits what, in Kantian terms, might be called a "negative utility" with respect to physical science. A further investigation of the anti-reductionist utility of Cassirer's systematic philosophy with respect to physics and other "symbolic forms" is finally suggested.     

On “the application of science to science itself:” chemistry,instruments, and the scientific labor process

The “Instrumental Revolution” in chemistry refers to a transitional period in the mid-20th century during which sophisticated instrumentation based on physical principles was introduced to solve chemical problems. Historical and philosophical reflection on whether the revolution was a scientific one has been dominated by general models of scientific revolution, in particular, those proposed by Thomas Kuhn, I. B. Cohen and Ian Hacking. In this article I propose that the Industrial Revolution is a useful model for understanding the transformation wrought by the increasingly important role of machines in chemical research. Drawing on Marx's analysis of that event, I argue that that the Instrumental Revolution bears a striking resemblance to the industrial one. I offer grounds for thinking that the resemblance is not fortuitous, but rather reflects a general pattern of development involving the mechanization of the labor process. It is suggested that the cognitive consequences of radical changes in the means of production, as exemplified in the Instrumental Revolution, warrant the consideration of whether the latter is an instance of a kind of revolution in science rather than a singular episode.     

A phenomenological solution to the measurement problem? Husserl and the foundations of quantum mechanics

The London and Bauer monograph occupies a central place in the debate concerning the quantum measurement problem. Gavroglu has previously noted the influence of Husserlian phenomenology on London's scientific work. However, he has not explored the full extent of this influence in the monograph itself. I begin this paper by outlining the important role played by the monograph in the debate. In effect, it acted as a kind of ‘lens’ through which the standard, or Copenhagen, ‘solution’ to the measurement problem came to be perceived and, as such, it was robustly criticized, most notably by Putnam and Shimony. I then spell out the Husserlian understanding of consciousness in order to illuminate the traces of this understanding within the London and Bauer text. This, in turn, yields a new perspective on this ‘solution’ to the measurement problem, one that I believe has not been articulated before and, furthermore, which is immune to the criticisms of Putnam and Shimony.     

The role of the thioredoxin/thioredoxin reductase system in the metabolic syndrome: towards a possible prognostic marker?

Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported.     

Perfusion studies employing α-C14 acetate to study the synergistic effect of cortisone and insulin on lipogenesis

Zusammenfassung Der vorliegende Aufsatz berichtet über Beobachtungen eines synergistischen Effektes von Insulin und Cortison bei der Fetts?uresynthese in der durchstr?mten Rattenleber. Dabei wurde Natrium-α¹⁴-C-acetat als Tracer verwendet und um Acetat bei der Biosynthese von Cholesterin und Fetts?uren aus dem Zweierbruchstück zu vertreten. Nach Lyophilisation der Leber, Extraktion und Fraktionierung der Lipide wurde gefunden, dass ins Cholesterin der mit Cortison behandelten Leber mehr radioaktiver Kohlenstoff eingetreten war, bei der Behandlung mit Insulin dagegen mehr in die Fetts?uren und schliesslich in dieselben doppelt soviel als ins Cholesterin bei Behandlung mit Insulin und Cortison zusammen. Der Anstieg nach Anwendung von Insulin allein dürfte auf Spuren von Nebennierenrindenhormonen zurückzuführen sein, welche noch in Leber und Blut vorhanden waren. Demnach darf angenommen werden, dass Cortison und Insulin, wenn sie gleichzeitig zur Wirkung kommen, von grossem Einfluss auf die Verwendbarkeit der Zweierbruchstücke sind. Der Anstieg der Cholesterinsynthese nach Behandlung mit Cortison ist durchaus bedeutungsvoll im Hinblick auf neuere Beobachtungen über Hypercholesterin?mien, welche w?hrend Cortisontherapie auftreten.      

The metaphysics of D-CTCs: On the underlying assumptions of Deutsch׳s quantum solution to the paradoxes of time travel

I argue that Deutsch׳s model for the behavior of systems traveling around closed timelike curves (CTCs) relies implicitly on a substantive metaphysical assumption. Deutsch is employing a version of quantum theory with a significantly supplemented ontology of parallel existent worlds, which differ in kind from the many worlds of the Everett interpretation. Standard Everett does not support the existence of multiple identical copies of the world, which the D-CTC model requires. This has been obscured because he often refers to the branching structure of Everett as a “multiverse”, and describes quantum interference by reference to parallel interacting definite worlds. But he admits that this is only an approximation to Everett. The D-CTC model, however, relies crucially on the existence of a multiverse of parallel interacting worlds. Since his model is supplemented by structures that go significantly beyond quantum theory, and play an ineliminable role in its predictions and explanations, it does not represent a quantum solution to the paradoxes of time travel.     

Multiple realization and multiple “ways” of realization: A progress report

One might have thought that if something has two or more distinct realizations, then that thing is multiply realized. Nevertheless, some philosophers have claimed that two or more distinct realizations do not amount to multiple realization, unless those distinct realizations amount to multiple “ways” of realizing the thing. Corey Maley, Gualtiero Piccinini, Thomas Polger, and Lawrence Shapiro are among these philosophers. Unfortunately, they do not explain why multiple realization requires multiple “ways” of realizing. More significantly, their efforts to articulate multiple “ways” of realizing turn out to be problematic.     

Hepatic α-tocopherol binding protein in the rat: Absence of an effect of selenium deficiency on binding activity

Summary Selenium deficiency produces no effect on either the total content of or the binding properties of rat liver -tocopherol binding protein.     

Butyrate-induced reactivation of the fetal globin genes: A molecular treatment for theβ-hemoglobinophaties

The inherited -hemoglobinopathies (sickle cell disease and thalassemia) are the result of a mutation in the adult () globin gene. The fetal globin chain, encoded by the globin genes, can substitute for the mutated or defective globin chain, but expression of the globin gene is developmentally inactivated prior to birth. Reinducing expression of the normal fetal globin genes is a preferred method of ameliorating sickle cell disease and the thalassemias. Stimulation of as little as 4–8% fetal globin synthesis in the bone marrow can produce >20% fetal hemoglobin in the peripheral circulation, due to enhanced survival of red blood cells containing both sickle and fetal hemoglobin, compared to those containing sickle hemoglobin alone. Butyric acid and butyrate derivatives are generally safe compounds which induce fetal hemoglobin production by stimulating the promoter of the fetal globin genes. An initial trial with the parent compound, delivered as Arginine Butyrate, has demonstrated rapid stimulation of fetal globin expression to levels that have been shown to ameliorate these conditions. Phase 1 trials of an oral butyrate derivative with a long plasma half-life have just begun. These agents now provide a specific new apporach for ameliorating these classic molecular disorders and merit further investigation in larger patient populations.     

A suggested mechanism for the action of choline esters on animal organs,inferred from a study of the effect of choline-,β-methylcholine-, and thiocholine-esters

Résumé Le mécanisme d'action des esters carboxyliques de la choline commence, probablement, par une hydrolyse enzymatique provoquée par une des cholinestérases. Les produits de l'hydrolyse réagissent avec un facteur inconnu, dont la spécificité est cependant définissable par la structure du résidu cholinique.