We have achieved a residue‐level resolution of genetic interaction mapping – a technique that measures how the function of one gene is affected by the alteration of a second gene – by analyzing point mutations. Here, we describe how to interpret point mutant genetic interactions, and outline key applications for the approach, including interrogation of protein interaction interfaces and active sites, and examination of post‐translational modifications. Genetic interaction analysis has proven effective for characterizing cellular processes; however, to date, systematic high‐throughput (...) genetic interaction screens have relied on gene deletions or knockdowns, which limits the resolution of gene function analysis and poses problems for multifunctional genes. Our point mutant approach addresses these issues, and further provides a tool for in vivo structure‐function analysis that complements traditional biophysical methods. We also discuss the potential for genetic interaction mapping of point mutations in human cells and its application to personalized medicine. (shrink)

One of the fundamental problems of epistemology is to say when the evidence in an agent’s possession justifies the beliefs she holds. In this paper and its prequel, we defend the Bayesian solution to this problem by appealing to the following fundamental norm: Accuracy An epistemic agent ought to minimize the inaccuracy of her partial beliefs. In the prequel, we made this norm mathematically precise; in this paper, we derive its consequences. We show that the two core tenets of Bayesianism (...) follow from the norm, while the characteristic claim of the Objectivist Bayesian follows from the norm along with an extra assumption. Finally, we consider Richard Jeffrey’s proposed generalization of conditionalization. We show not only that his rule cannot be derived from the norm, unless the requirement of Rigidity is imposed from the start, but further that the norm reveals it to be illegitimate. We end by deriving an alternative updating rule for those cases in which Jeffrey’s is usually supposed to apply. (shrink)

One of the fundamental problems of epistemology is to say when the evidence in an agent’s possession justifies the beliefs she holds. In this paper and its sequel, we defend the Bayesian solution to this problem by appealing to the following fundamental norm: Accuracy An epistemic agent ought to minimize the inaccuracy of her partial beliefs. In this paper, we make this norm mathematically precise in various ways. We describe three epistemic dilemmas that an agent might face if she attempts (...) to follow Accuracy, and we show that the only inaccuracy measures that do not give rise to such dilemmas are the quadratic inaccuracy measures. In the sequel, we derive the main tenets of Bayesianism from the relevant mathematical versions of Accuracy to which this characterization of the legitimate inaccuracy measures gives rise, but we also show that Jeffrey conditionalization has to be replaced by a different method of update in order for Accuracy to be satisfied. (shrink)

This essay develops a joint theory of rational (all-or-nothing) belief and degrees of belief. The theory is based on three assumptions: the logical closure of rational belief; the axioms of probability for rational degrees of belief; and the so-called Lockean thesis, in which the concepts of rational belief and rational degree of belief figure simultaneously. In spite of what is commonly believed, this essay will show that this combination of principles is satisfiable (and indeed nontrivially so) and that the principles (...) are jointly satisfied if and only if rational belief is equivalent to the assignment of a stably high rational degree of belief. Although the logical closure of belief and the Lockean thesis are attractive postulates in themselves, initially this may seem like a formal “curiosity”; however, as will be argued in the rest of the essay, a very reasonable theory of rational belief can be built around these principles that is not ad hoc and that has various philosophical features that are plausible independently. In particular, this essay shows that the theory allows for a solution to the Lottery Paradox, and it has nice applications to formal epistemology. The price that is to be paid for this theory is a strong dependency of belief on the context, where a context involves both the agent's degree of belief function and the partitioning or individuation of the underlying possibilities. But as this essay argues, that price seems to be affordable. (shrink)

Many discussions between realists and non-realists have centered on the issue of reference, especially whether there is referential stability during theory change. In this paper, I shall summarize the debate, sketching the problems that remain within the two opposing positions, and show that both have ended on their own slippery slope, sliding away from their original position toward that of their opponents. In the search for a viable intermediate position, I shall then suggest an account of reference which, to a (...) degree, follows the causal theory in explaining reference as carving the world at its joints. Contrary to the causal theory, however, I submit that this world is a phenomenal world whose variable joints exist only in a historical process in which they are transmitted gradually from one generation to the next. According to this account, the joints of the phenomenal world are constituted by family resemblance, where bundles of features that span bounded areas in perceptual space underlie the joints. Furthermore, the integrity of the cognitive process by which these joints are recognized depends on a transmission process by which new generations are presented with given joints and bundles by the preceding generation. Contrary to a traditional realist account, this heritage from the preceding generation may be transformed into new joints and bundles before transmission to new generations. This permits a continuous process of referential change in which the joints and bundles at different stages in the development of a theory can be connected by chains-of-reasoning. (shrink)

In discussions about whether the Principle of the Identity of Indiscernibles is compatible with structuralist ontologies of mathematics, it is usually assumed that individual objects are subject to criteria of identity which somehow account for the identity of the individuals. Much of this debate concerns structures that admit of non-trivial automorphisms. We consider cases from graph theory that violate even weak formulations of PII. We argue that (i) the identity or difference of places in a structure is not to be (...) accounted for by anything other than the structure itself and that (ii) mathematical practice provides evidence for this view. We want to thank Leon Horsten, Jeff Ketland, Øystein Linnebo, John Mayberry, Richard Pettigrew, and Philip Welch for valuable comments on drafts of this paper. We are especially grateful to Fraser MacBride for correcting our interpretation of two of his papers and for other helpful comments. CiteULike Connotea Del.icio.us What's this? (shrink)

This article introduces, studies, and applies a new system of logic which is called ‘HYPE’. In HYPE, formulas are evaluated at states that may exhibit truth value gaps and truth value gluts. Simple and natural semantic rules for negation and the conditional operator are formulated based on an incompatibility relation and a partial fusion operation on states. The semantics is worked out in formal and philosophical detail, and a sound and complete axiomatization is provided both for the propositional and the (...) predicate logic of the system. The propositional logic of HYPE is shown to contain first-degree entailment, to have the Finite Model Property, to be decidable, to have the Disjunction Property, and to extend intuitionistic propositional logic conservatively when intuitionistic negation is defined appropriately by HYPE’s logical connectives. Furthermore, HYPE’s first-order logic is a conservative extension of intuitionistic logic with the Constant Domain Axiom, when intuitionistic negation is again defined appropriately. The system allows for simple model constructions and intuitive Euler-Venn-like diagrams, and its logical structure matches structures well-known from ordinary mathematics, such as from optimization theory, combinatorics, and graph theory. HYPE may also be used as a general logical framework in which different systems of logic can be studied, compared, and combined. In particular, HYPE is found to relate in interesting ways to classical logic and various systems of relevance and paraconsistent logic, many-valued logic, and truthmaker semantics. On the philosophical side, if used as a logic for theories of type-free truth, HYPE is shown to address semantic paradoxes such as the Liar Paradox by extending non-classical fixed-point interpretations of truth by a conditional as well-behaved as that of intuitionistic logic. Finally, HYPE may be used as a background system for modal operators that create hyperintensional contexts, though the details of this application need to be left to follow-up work. (shrink)

Impaired performance in verbal fluency tasks is a frequent observation in Parkinson’s disease. As to the nature of the underlying cognitive deficit, it is commonly attributed to a frontal-type dysexecutive syndrome due to nigrostriatal dopamine depletion. Whereas dopaminergic medication typically improves VF performance in PD, e.g., by ameliorating impaired lexical switching, its effect on semantic network activation is unclear. Data from priming studies suggest that dopamine causes a faster decay of semantic activation spread. The aim of the current study was (...) to examine the impact of dopaminergic medication on the dynamic change of word frequency during VF performance as a measure of semantic spreading activation. To this end, we performed a median split analysis of word frequency during phonemic and semantic VF task performance in a PD group tested while receiving dopaminergic medication as well as after drug withdrawal, and in a sample of age-matched healthy volunteers. Dopaminergic medication in the PD group significantly affected phonemic VF with improved word production as well as increased error-rates. The expected decrease of word frequency during VF task performance was significantly smaller in the PD group ON medication than in healthy volunteers across semantic and phonemic VF. No significant group-difference emerged between controls and the PD group in the OFF condition. The comparison between both treatment conditions within the PD group did not reach statistical significance. The observed pattern of results indicates a faster decay of semantic network activation during lexical access in PD patients on dopaminergic medication. In view of improved word generation, this finding is consistent with a concept of more focused neural activity by an increased signal-to-noise ratio due to dopaminergic neuromodulation. However, the effect of dopaminergic stimulation on VF output suggests a trade-off between these beneficial effects and increased error-rates. (shrink)

This article outlines what a formal theory of truth should be like, at least at first glance. As not all of the stated constraints can be satisfied at the same time, in view of notorious semantic paradoxes such as the Liar paradox, we consider the maximal consistent combinations of these desiderata and compare their relative advantages and disadvantages.

Is it possible to give an explicit definition of belief in terms of subjective probability, such that believed propositions are guaranteed to have a sufficiently high probability, and yet it is neither the case that belief is stripped of any of its usual logical properties, nor is it the case that believed propositions are bound to have probability 1? We prove the answer is ‘yes’, and that given some plausible logical postulates on belief that involve a contextual “cautiousness” threshold, there (...) is but one way of determining the extension of the concept of belief that does the job. The qualitative concept of belief is not to be eliminated from scientific or philosophical discourse, rather, by reducing qualitative belief to assignments of resiliently high degrees of belief and a “cautiousness” threshold, qualitative and quantitative belief turn out to be governed by one unified theory that offers the prospects of a huge range of applications. Within that theory, logic and probability theory are not opposed to each other but go hand in hand. (shrink)

Epidemiological studies of chronic diseases began around the mid-20th century. Contrary to the infectious disease epidemiology which had prevailed at the beginning of the 20th century and which had focused on single agents causing individual diseases, the chronic disease epidemiology which emerged at the end of Word War II was a much more complex enterprise that investigated a multiplicity of risk factors for each disease. Involved in the development of chronic disease epidemi-ology were therefore fundamental discussions on the notion of (...) causality, especially the question when causal inferences could be justified. In this paper, I shall analyze the implicit normativity of these de-bates. First, I shall give a brief overview of the historical background on which chronic disease epi-demiology emerged and describe how the pioneer studies on smoking and lung cancer became icon of the major challenge that the emerging chronic disease epidemiology was facing: the impossibility of proving that statistical associations reflected causal relations. Next, I shall describe how the develop-ment from the monocausal enterprise of infectious disease epidemiology to the multicausal enterprise of chronic disease epidemiology gave rise to intense discussions of the possible criteria by which to establish causal relationships between a given factor and a particular disease. I shall show how the necessary and sufficient conditions expressed in the so-called Henle-Koch criteria that had proved useful for the 19th century investigations of infectious diseases remained an ideal, although clearly an unobtainable one. Thus, I shall show how 20th century chronic disease epidemiologists on the one hand were searching for a new set of general principles which would provide a logical framework for their investigations, but on the other hand admitted that they would have to accept something more "pragmatic". I shall analyze the various positions in this debate, arguing that the implacability of the debate was due to unrecognized normative issues. I shall argue that many insisted on a distinction between science and application that was untenable, but that due to this distinction the values in-volved in deciding whether or not to act on the basis of a hypothesis were rarely explicitly discussed and the decision therefore continued to appear as a matter of taste rather than the result of a cogent normative analysis. (shrink)

The article recapitulates what logic is about traditionally and works out two roles it has been playing in philosophy: the role of an instrument and of a philosophical discipline in its own right. Using Tarski’s philosophical-logical work as case study, it develops a logical reconstructionist methodology of philosophical logic that extends and refines Rudolf Carnap’s account of explication and rational reconstruction. The methodology overlaps with, but also partially diverges from, contemporary anti-exceptionalism about logic.

The aim of this paper is to argue for a revised and precisified version of the infamous Verifiability Criterion for the meaningfulness of declarative sentences. The argument is based on independently plausible premises concerning probabilistic confirmation and meaning as context-change potential, it is shown to be logically valid, and its ramifications for potential applications of the criterion are being discussed. Although the paper is not historical but systematic, the criterion thus vindicated will resemble the original one(s) in some important ways. (...) At the same time, it will also be more modest insofar as meaningfulness will turn out to be relativized linguistically and probabilistically, and different choices of the linguistic and probabilistic parameters may lead to different verdicts on meaningfulness. (shrink)

In everyday life we either express our beliefs in all-or-nothing terms or we resort to numerical probabilities: I believe it's going to rain or my chance of winning is one in a million. The Stability of Belief develops a theory of rational belief that allows us to reason with all-or-nothing belief and numerical belief simultaneously.

This is part A of a paper in which we defend a semantics for counterfactuals which is probabilistic in the sense that the truth condition for counterfactuals refers to a probability measure. Because of its probabilistic nature, it allows a counterfactual ‘ifAthenB’ to be true even in the presence of relevant ‘Aand notB’-worlds, as long such exceptions are not too widely spread. The semantics is made precise and studied in different versions which are related to each other by representation theorems. (...) Despite its probabilistic nature, we show that the semantics and the resulting system of logic may be regarded as a naturalistically vindicated variant of David Lewis’ truth-conditional semantics and logic of counterfactuals. At the same time, the semantics overlaps in various ways with the non-truth-conditional suppositional theory for conditionals that derives from Ernest Adams’ work. We argue that counterfactuals have two kinds of pragmatic meanings and come attached with two types of degrees of acceptability or belief, one being suppositional, the other one being truth based as determined by our probabilistic semantics; these degrees could not always coincide due to a new triviality result for counterfactuals, and they should not be identified in the light of their different interpretation and pragmatic purpose. However, for plain assertability the difference between them does not matter. Hence, if the suppositional theory of counterfactuals is formulated with sufficient care, our truth-conditional theory of counterfactuals is consistent with it. The results of our investigation are used to assess a claim considered by Hawthorne and Hájek, that is, the thesis that most ordinary counterfactuals are false. (shrink)

This is Part B of an article that defends non-eliminative structuralism about mathematics by means of a concrete case study: a theory of unlabeled graphs. Part A motivated an understanding of unlabeled graphs as structures sui generis and developed a corresponding axiomatic theory of unlabeled graphs. Part B turns to the philosophical interpretation and assessment of the theory: it points out how the theory avoids well-known problems concerning identity, objecthood, and reference that have been attributed to non-eliminative structuralism. The part (...) concludes by explaining how the theory relates to set theory, and what remains to be accomplished for non-eliminative structuralists. (shrink)

This book takes a distinctive and innovative approach to a relatively under-explored question, namely: Why do we have human rights? Much political discourse simply proceeds from the idea that humans have rights because they are human without seriously interrogating this notion. Egalitarian Rights Recognition offers an account of how human rights are created and how they may be seen to be legitimate: rights are created through social recognition. By combining readings of 19th Century English philosopher T.H. Green with 20th Century (...) political theorist Hannah Arendt, the author constructs a new theory of the social recognition of rights. He challenges both the standard ‘natural rights’ approach and also the main accounts of the social recognition of rights which tend to portray social recognition as settled norms or established ways of acting. In contrast, Hann puts forward a 10-point account of the dynamic and contingent social recognition of human rights, which emphasises the importance of meaningful socio-economic equality. (shrink)

On the basis of impossibility results on probability, belief revision, and conditionals, it is argued that conditional beliefs differ from beliefs in conditionals qua mental states. Once this is established, it will be pointed out in what sense conditional beliefs are still conditional, even though they may lack conditional contents, and why it is permissible to still regard them as beliefs, although they are not beliefs in conditionals. Along the way, the main logical, dispositional, representational, and normative properties of conditional (...) beliefs are studied, and it is explained how the failure of not distinguishing conditional beliefs from beliefs in conditionals can lead philosophical and empirical theories astray. (shrink)

This is Part A of an article that defends non-eliminative structuralism about mathematics by means of a concrete case study: a theory of unlabeled graphs. Part A summarizes the general attractions of non-eliminative structuralism. Afterwards, it motivates an understanding of unlabeled graphs as structures sui generis and develops a corresponding axiomatic theory of unlabeled graphs. As the theory demonstrates, graph theory can be developed consistently without eliminating unlabeled graphs in favour of sets; and the usual structuralist criterion of identity can (...) be applied successfully in graph-theoretic proofs. Part B will turn to the philosophical interpretation and assessment of the theory. (shrink)

This papers deals with the class of axiomatic theories of truth for semantically closed languages, where the theories do not allow for standard models; i.e., those theories cannot be interpreted as referring to the natural number codes of sentences only (for an overview of axiomatic theories of truth in general, see Halbach[6]). We are going to give new proofs for two well-known results in this area, and we also prove a new theorem on the nonstandardness of a certain theory of (...) truth. The results indicate that the proof strategies for all the theorems on the nonstandardness of such theories are "essentially" of the same kind of structure. (shrink)

Pure mathematical truths are commonly thought to be metaphysically necessary. Assuming the truth of pure mathematics as currently pursued, and presupposing that set theory serves as a foundation of pure mathematics, this article aims to provide a metaphysical explanation of why pure mathematics is metaphysically necessary.

The thesis defended in this article is that by uttering or publishing a great many declarative sentences in assertoric mode, one does not actually assert that their conjunction is true – one rather asserts that the vast majority of these sentences are true. Accordingly, the belief that is expressed thereby is the belief that the vast majority of these sentences are true. In the article, we make this proposal precise, we explain the context-dependency of belief that corresponds to it, we (...) point out why our everyday oral practice of single assertions is not affected by it, and we argue that the proposal leads to a way out of the Paradox of the Preface. (shrink)

Recently, several scholars have argued that scientists can accept scientific claims in a collective process, and that the capacity of scientific groups to form joint acceptances is linked to a functional division of labor between the group members. However, these accounts reveal little about how the cognitive content of the jointly accepted claim is formed, and how group members depend on each other in this process. In this paper, I shall therefore argue that we need to link analyses of joint (...) acceptance with analyses of distributed cognition. To sketch how this can be done, I shall present a detailed case study, and on the basis of the case, analyze the process through which a group of scientists jointly accept a new scientific claim and at a later stage jointly accept to revise previously accepted claims. I shall argue that joint acceptance in science can be established in situations where an overall conceptual structure is jointly accepted by a group of scientists while detailed parts of it are distributed among group members with different areas of expertise, a condition that I shall call a heterogeneous conceptual consensus. Finally, I shall show how a heterogeneous conceptual consensus can work as a constraint against scientific change and address the question how changes may nevertheless occur. (shrink)

Slavoj Zizek’s criticism of Western Buddhism (2014) for being a late capitalist opiate of the people is partly unwarranted and partly of undeniable relevance. His implicit assumption is that Buddhism is an internalist path that only looks into the individual inner world, leaving harmful societal systems in peace. This article offers a response to Zizek’s analysis, by interpreting the chariot simile in the Buddhist Pali Canon. Even though Pali chariot similes indeed support an internalist perspective, some of them also allow (...) for a reading that opens up to two “externalist” complements: the social outer world and the technological environment. In this way, while acknowledging Zizek’s criticism, we point at Buddhist philosophy’s inherent potential for developing a social-technological critical stance, for instance by linking it to mediation theory. (shrink)

This is a personal, incomplete, and very informal take on the role of logic in general philosophy of science, which is aimed at a broader audience. We defend and advertise the application of logical methods in philosophy of science, starting with the beginnings in the Vienna Circle and ending with some more recent logical developments.

The literatures on both authentic leadership and behavioral integrity have argued that leader integrity drives follower performance. Yet, despite overlap in conceptualization and mechanisms, no research has investigated how authentic leadership and behavioral integrity relate to one another in driving follower performance. In this study, we propose and test the notion that authentic leadership behavior is an antecedent to perceptions of leader behavioral integrity, which in turn affects follower affective organizational commitment and follower work role performance. Analysis of a survey (...) of 49 teams in the service industry supports the proposition that authentic leadership is related to follower affective organizational commitment, fully mediated through leader behavioral integrity. Next, we found that authentic leadership and leader behavioral integrity are related to follower work role performance, fully mediated through follower affective organizational commitment. These relationships hold when controlling for ethical organizational culture. (shrink)