Inferentialism as a theory of meaning builds on the idea that what a linguistic expression means depends exclusively on the inferential rules that govern its use. Following different strategies and exploring various case studies, the authors of this collection of essays discuss under what circumstances and to what extent the central tenets of inferentialism are tenable. The essays in this volume present the results of a three-year research project "Representation and Inference" which was conducted from the beginning of 2008 to (...) the end 2010. The aim of the project was to assess the research program of inferentialism as it has been pursued recently by Robert Brandom, Mark Lance, and Jaroslav Peregrin. Earlier versions of these texts were presented at the conference "Inference, Consequence, and Meaning" held in Sofia on the 3rd and 4th of December, 2008. (shrink)

Phenotypic plasticity is a crucial feature of aggressive cancer, providing the means for cancer progression. Stochastic changes in tumor cell transcriptional programs increase the chances of survival under any condition. I hypothesize that unstable chromatin permits stochastic transitions between transcriptional programs in aggressive cancers and supports non‐genetic heterogeneity of tumor cells as a basis for their adaptability. I present a mechanistic model for unstable chromatin which includes destabilized nucleosomes, mobile chromatin fibers and random enhancer‐promoter contacts, resulting in stochastic transcription. I (...) suggest potential markers for “unsettled” chromatin in tumors associated with poor prognosis. Although many of the characteristics of unstable chromatin have been described, they were mostly used to explain changes in the transcription of individual genes. I discuss approaches to evaluate the role of unstable chromatin in non‐genetic tumor cell heterogeneity and suggest using the degree of chromatin instability and transcriptional noise in tumor cells to predict cancer aggressiveness. (shrink)

In this essay, I propose that DNA‐binding anti‐cancer drugs work more via chromatin disruption than DNA damage. Success of long‐awaited drugs targeting cancer‐specific drivers is limited by the heterogeneity of tumors. Therefore, chemotherapy acting via universal targets (e.g., DNA) is still the mainstream treatment for cancer. Nevertheless, the problem with targeting DNA is insufficient efficacy due to high toxicity. I propose that this problem stems from the presumption that DNA damage is critical for the anti‐cancer activity of these drugs. DNA (...) in cells exists as chromatin, and many DNA‐targeting drugs alter chromatin structure by destabilizing nucleosomes and inducing histone eviction from chromatin. This effect has been largely ignored because DNA damage is seen as the major reason for anti‐cancer activity. I discuss how DNA‐binding molecules destabilize chromatin, why this effect is more toxic to tumoral than normal cells, and why cells die as a result of chromatin destabilization. (shrink)

One of the most lively debates on scientific understanding is standardly presented as a controversy between the so-called factivists, who argue that understanding implies truth, and the non-factivists whose position is that truth is neither necessary nor sufficient for understanding. A closer look at the debate, however, reveals that the borderline between factivism and non-factivism is not as clear-cut as it looks at first glance. Some of those who claim to be quasi-factivists come suspiciously close to the position of their (...) opponents, the non-factivist, from whom they pretend to differ. The non-factivist, in turn, acknowledges that some sort of ‘answering to the facts’ is indispensable for understanding. This paper discusses an example of convergence of the initially rival positions in the debate on understanding and truth: the use of the same substitute for truth by the quasi-factivist Kareem Khalifa and the non-factivists Henk de Regt and Victor Gijsbers. It is argued that the use of ‘effectiveness’ as a substitute for truth by both parties is not an occasional coincidence of terms, it rather speaks about a deeper similarity which have important implications for understanding the essential features of scientific understanding. (shrink)

In a series of recent publications Jerry Fodor has attacked what many believe is the core of Darwinian theory of evolution – the theory of natural selection. Not surprisingly, Fodor’s attack has provoked a strong negative reaction. Fodor’s critics have insisted both that his main argument is unsound and that his central claim that the theory of natural selection “can’t explain the distribution of phenotypic traits in biological populations” is untenable. I can generally agree with the first part of the (...) launched criticism: Fodor’s “putative argument” does rely on controversial premises which make it unsound. However, I don’t think that Fodor’s critics have succeeded in their attempts to refute his central claim. The refutation strategy that most of them have undertaken is to show examples of successful evolutionary explanations by natural selection. In what follows, two of these examples are put into scrutiny. The analysis reveals that: (1) The theory of natural selection should be only partially credited with the explanatory success of evolutionary explanations by natural selection because these explanations rely on additional empirical hypotheses which might be true or false. That means that the selectionist explanations are fallible statements the truth value of which depends crucially on the truth value of the empirical assumptions which have been premised. (2) In both cases alternative non-selectionist explanations can be found that fit the same empirical data and no reason has been given (or could be given) why these alternative explanations should be ignored a priori as inferior. The observations (1) and (2) stand against the claim that theory of natural selection is the only legitimate explanance for the distribution of phenotypic traits. This does not mean, of course, that natural selection does not play any explanatory role or that the theory of natural selection is a false theory (as Fodor is inclined to argue for). This only means that there is indeed a problem of understanding the proper explanatory role of natural selection and that this problem is not only Fodor’s problem. The paper ends with a suggestion of what should be admitted in order to get to a better understanding of the proper role that the theory of natural selection plays in evolutionary explanations. (shrink)

The central argument in this paper is the following: if we agree that one of the aims of explanation is to provide or increase understanding, and if we assess understanding on the basis of the inferences one can draw from the knowledge of the phenomenon which is understood, then the value of an explanation, i.e. its capacity to provide or increase understanding of the explained phenomenon, should be assessed on the basis of the extra-inferences which this explanation allows for. The (...) extra-inferences which a given explanation allows for constitute its inferential content. The analysis of the explanation’s inferential content could be applied to all kinds of explanations with the aim of assessing their goodness. I show how such an analysis helps us to better understand a number of difficulties that have puzzled contemporary philosophers of explanation: the flagpole counterexample to the deductive-nomological model of explanation, the conjunction problem, the difference between good and bad circular explanations. (shrink)

On observe une nouvelle tendance dans la philosophie des sciences cognitives, manifeste dans les écrits de Betchel et al. qui met en avant l’importance des explications mécanistes au détriment du rôle explicatif des principes. Cet article est un plaidoyer pour rétablir l’équilibre. Il met l’accent sur l’effort d’explication des effets du niveau de base, l’une des plus importantes découvertes empiriques dans l’histoire de la recherche en catégorisation. L’analyse de trois différentes périodes de cette histoire révèle que le recours aux principes (...) y a joué un rôle crucial. Cependant, afin de reconnaître pleinement le rôle explicatif des principes, nous devrions nous préparer à admettre que les explications déductives-nomologiques ne sont pas les seuls types d’explications basées sur des principes. (shrink)

On observe une nouvelle tendance dans la philosophie des sciences cognitives, manifeste dans les écrits de Betchel et al. qui met en avant l’importance des explications mécanistes au détriment du rôle explicatif des principes. Cet article est un plaidoyer pour rétablir l’équilibre. Il met l’accent sur l’effort d’explication des effets du niveau de base, l’une des plus importantes découvertes empiriques dans l’histoire de la recherche en catégorisation. L’analyse de trois différentes périodes de cette histoire révèle que le recours aux principes (...) y a joué un rôle crucial. Cependant, afin de reconnaître pleinement le rôle explicatif des principes, nous devrions nous préparer à admettre que les explications déductives-nomologiques ne sont pas les seuls types d’explications basées sur des principes. (shrink)

Graphical AbstractWith DNA damage being a primary anti-cancertarget, a need has arisen for the development of an approach that is a harmlessfor normal tissues but allows for cancer cell-specific cytotoxicity. Previous researchfrom K. Gurova's suggests that small compounds, namely curaxins that bind theDNA can cause chromatin instability and cell death in a cancer cell-specificmanner. In this brief perspective commentary, we investigate how the scientificcommunity has further developed this anti-cancer approach.