Pictures of sounds: Wittgenstein on gramophone records and the logic of depiction

I consider the way Wittgenstein employed some kinds of sound recordings (but not others) in discussing logical form in the Tractatus logico-philosophicus. The year that Ludwig Wittgenstein was born in Vienna, 1889, nearby developments already underway portended two major changes of the coming century: the advent of controlled heavier than air flight and the mass production of musical sound recordings. Before they brought about major social changes, though, these innovations appeared in Europe in the form of children’s toys. Wittgenstein uses the fact that a symphony performance can be constructed from both a written musical score and the grooves of a gramophone record to explain what logical form is. His characterization of logical form in the Tractatus in terms of intertranslatability rather than in terms of interpretability is highlighted by reflecting on the kinds of examples of sound recordings that he did not use to illustrate the notion of logical form. There were other well known technologies for making visual records of sound at the time, but these did not serve to illustrate logical form.     

The role of forecasting in corporate strategy: The xerox experience

This paper presents the system of analysis used by the Xerox Corporation to relate the external environment to company decisions. The system is sophisticated and elaborate, comes to grips with such issues as product forecasting, market monitoring, activity monitoring, materials and labour cost analysis, and product price analysis. In addition, the system examines the longer-term issues associated with corporate strategy, with the more recent initiatives directed toward the strategic focus The Xerox case illustrates very well how externally provided forecasts of economic environments, both at home and abroad, can be used as inputs to a variety of econometric products to serve the individual corporation. The challenge in this work is to build the bridges from the external forces to the critical company decisions. That is a task which requires sophisticated tools and skilled professionals to accomplish. This case study shows what can be done.     

The early history of ship magnetism: The Airy-Scoresby controversy

With the advent of iron-built ships in the early nineteenth century the problem of managing a magnetic compass on board presented considerable difficulty. Prominent among the early scientists who tackled the problem were George Biddell Airy and William Scoresby. Airy had provided a mechanical system, employing correctors in the form of steel magnets and wrought iron masses, by which the ship's magnetic field at the compass position is neutralized. He based his system on the concept that the magnetism acquired by an iron ship during her construction remained with the ship throughout her life. Scoresby, on the other hand, thought differently. After having conducted a thorough and systematic series of experiments on iron plates and bars, he concluded that the magnetic character of an iron ship is liable to sudden and unexpected change. Scoresby argued, therefore, that Airy's system was defective and, indeed, dangerous. The aim of this paper is to discuss the two views which brought Airy and Scoresby into a conflict which is documented in a series of letters to the editor of The Athenaeum.     

The balance between immunity and tolerance: The role of Langerhans cells

Langerhans cells are immature skin-homing dendritic cells that furnish the epidermis with an immune surveillance system, and translate information between the internal and external milieu. Dendritic cells, in particular Langerhans cells, are gaining prominence as one of the potential principal players orchestrating the decision between immunity and tolerance. Langerhans cells capture aberrant self-antigen and pathogen-derived antigen for display to the efferent immune response. Recent evidence suggests redundancy in the antigen-presenting function of Langerhans cells, with dermal dendritic subsets capable of fulfilling an analogous role. There is mounting evidence that Langerhans cells can cross-prime T cells to recognize antigens. Langerhans cells are proposed to stimulate T regulatory cells, and are implicated in the pathogenesis of cutaneous T cell lymphoma.The phenotype of Langerhans cells, which may be tolerogenic or immunogenic, appears to depend on their state of maturity, inciting immunogen and cytokine environment, offering the potential for manipulation in immunotherapy. Received 6 August 2008; received after revision 18 September 2008; accepted 13 October 2008     

The explanatory role of abstraction processes in models: The case of aggregations

Though it is held that some models in science have explanatory value, there is no conclusive agreement on what provides them with this value. One common view is that models have explanatory value vis-à-vis some target systems because they are developed using an abstraction process (i.e., a process which involves omitting features). Though I think this is correct, I believe it is not the whole picture. In this paper, I argue that, in addition to the well-known process of abstraction understood as an omission of features or information, there is also a family of abstraction processes that involve aggregation of features or information and that these processes play an important role in endowing the models they are used to build with explanatory value. After offering a taxonomy of abstraction processes involving aggregation, I show by considering in detail several models drawn from different sciences that the abstraction processes involving aggregation that are used to build these models are responsible (at least partially) for their having explanatory value.     

The role of psychology in behavioral economics: The case of social preferences

Behavioral economics is a field of study that is often thought of as interdisciplinary, insofar as it uses psychological insights to inform economic models. Yet the level of conceptual and methodological exchange between the two disciplines is disputed in the literature. On the one hand, behavioral economic models are often presented as psychologically informed models of individual decision-making (Camerer & Loewenstein, 2003). On the other hand, these models have often been criticized for being merely more elaborated “as if” economic models (Berg & Gigerenzer, 2010). The aim of this paper is to contribute to this debate by looking at a central topic in behavioral economics: the case of social preferences. Have findings or research methods been exchanged between psychology and economics in this research area? Have scientists with different backgrounds “travelled” across domains, thus transferring their expertise from one discipline to another? By addressing these and related questions, this paper will assess the level of knowledge transfer between psychology and economics in the study of social preferences.     

The role of HLA-G in immunity and hematopoiesis

The non-classical HLA class I molecule HLA-G was initially shown to play a major role in feto–maternal tolerance. Since this discovery, it has been established that HLA-G is a tolerogenic molecule which participates to the control of the immune response. In this review, we summarize the recent advances on (1) the multiple structures of HLA-G, which are closely associated with their role in the inhibition of NK cell cytotoxicity, (2) the factors that regulate the expression of HLA-G and its receptors, (3) the mechanism of action of HLA-G at the immunological synapse and through trogocytosis, and (4) the generation of suppressive cells through HLA-G. Moreover, we also review recent findings on the non-immunological functions of HLA-G in erythropoiesis and angiogenesis.     

The early and late processing of lysosomal enzymes: proteolysis and compartmentation.

Lysosomal enzymes are subjected to a number of modifications including carbohydrate restructuring and proteolytic maturation. Some of these reactions support lysosomal targeting, others are necessary for activation or keeping the enzyme inactive before being segregated, while still others may be adventitious. The non-segregated fraction of the enzyme is secreted and can be isolated from the medium. It is considered that the secreted lysosomal enzymes fulfill certain physiological and pathophysiological roles. By comparing the secreted and the intracellular enzymes it is possible to distinguish between the reactions that occur before and after the segregation. In this review the reactions that may influence the segregation are referred to as the early processing and those characteristic for the enzymes isolated from lysosomal compartments as the late processing. The early processing is characterized mainly by modifications of carbohydrate side chains. In the late processing, proteolytic fragmentation represents the most conspicuous changes. The review focuses on the compartmentation of the reactions and the proteolytic fragmentation of lysosomal enzyme precursors. While a plethora of proteolytic reactions are involved, our knowledge of the proteinases responsible for the particular maturation reactions remains very limited. The review points also to work with cells from patients affected with lysosomal storage disorders, which contributed to our understanding of the lysosomal apparatus.     

The treatment of observations in early astronomy

Communicated by Curtis Wilson     

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis.     

The early history of chance in evolution

Work throughout the history and philosophy of biology frequently employs ‘chance’, ‘unpredictability’, ‘probability’, and many similar terms. One common way of understanding how these concepts were introduced in evolution focuses on two central issues: the first use of statistical methods in evolution (Galton), and the first use of the concept of “objective chance” in evolution (Wright). I argue that while this approach has merit, it fails to fully capture interesting philosophical reflections on the role of chance expounded by two of Galton's students, Karl Pearson and W.F.R. Weldon. Considering a question more familiar from contemporary philosophy of biology—the relationship between our statistical theories of evolution and the processes in the world those theories describe—is, I claim, a more fruitful way to approach both these two historical actors and the broader development of chance in evolution.     

Correction to: The role of connexin proteins and their channels in radiation-induced atherosclerosis

Cellular and Molecular Life Sciences - A correction to this paper has been published: https://doi.org/10.1007/s00018-021-03811-z     

The role of repair in radiobiology

Apart from cancer and mutation induction, radiobiological effects on mammals are mostly attributable to cell 'death', defined as loss of proliferative capacity. Survival curves relate retention of that capacity to radiation dose, and often manifest a quasi-threshold ('shoulder'). The shoulder is attributable to an initial mechanism of repair ('Q-repair') which is gradually depleted as dose increases. Another form of repair, which is not depleted ('P-repair'), increases the dose required to deliver an average of one lethal event per cell (dose 'D0'). Neither form of repair can unambiguously be linked with repair of defects in isolated DNA. An important initial lesion may well be disruption of the complex structural relationship between the DNA, nuclear membrane and associated proteins. One form of P-repair may be restoration of that structural relationship.     

The role of phosphoenolpyruvate in insulin secretion: the effect of L-phenylalanine

Summary Incubation of rat islets with phenylalanine increased the tissue content of phosophoenolpyruvate, both in the presence and in the absence of glucose. At the same time, L-phenylalanine neither stimulated nor inhibited insulin release. It is unlikely that insulin secretion is tightly coupled to the availability of phosphoenolpyruvate in rat islets.     

The diffusion of scientific innovations: A role typology

How do scientific innovations spread within and across scientific communities? In this paper, we propose a general account of the diffusion of scientific innovations. This account acknowledges that novel ideas must be elaborated on and conceptually translated before they can be adopted and applied to field-specific problems. We motivate our account by examining an exemplary case of knowledge diffusion, namely, the early spread of theories of rational decision-making. These theories were grounded in a set of novel mathematical tools and concepts that originated in John von Neumann and Oskar Morgenstern's Theory of Games and Economic Behavior (1944/1947) and subsequently spread widely across the social and behavioral sciences. Introducing a network-based diffusion measure, we trace the spread of those tools and concepts into distinct research areas. We furthermore present an analytically tractable typology for classifying publications according to their roles in the diffusion process. The proposed framework allows for a systematic examination of the conditions under which scientific innovations spread within and across preexisting and newly emerging scientific communities.     

Forecasting US GNP growth: The role of uncertainty

A large number of models have been developed in the literature to analyze and forecast changes in output dynamics. The objective of this paper was to compare the predictive ability of univariate and bivariate models, in terms of forecasting US gross national product (GNP) growth at different forecasting horizons, with the bivariate models containing information on a measure of economic uncertainty. Based on point and density forecast accuracy measures, as well as on equal predictive ability (EPA) and superior predictive ability (SPA) tests, we evaluate the relative forecasting performance of different model specifications over the quarterly period of 1919:Q2 until 2014:Q4. We find that the economic policy uncertainty (EPU) index should improve the accuracy of US GNP growth forecasts in bivariate models. We also find that the EPU exhibits similar forecasting ability to the term spread and outperforms other uncertainty measures such as the volatility index and geopolitical risk in predicting US recessions. While the Markov switching time‐varying parameter vector autoregressive model yields the lowest values for the root mean squared error in most cases, we observe relatively low values for the log predictive density score, when using the Bayesian vector regression model with stochastic volatility. More importantly, our results highlight the importance of uncertainty in forecasting US GNP growth rates.