When an agent can not recognize, immediately, the implausible part of new information received, she will usually first expand her belief state by the new information, and then she may encounter some belief conflicts, and find the implausible information based on her criteria to consolidate her belief state. This process indicates a new kind of non-prioritized multiple revision, called metabolic revision. I give some axiomatic postulates for metabolic revision and propose two functional constructions for it, (...) namely kernel metabolic revision and partial meet metabolic revision, with respect to which the representation theorems are proved. I also compare metabolic revision with some related works in the literature, including semi-revision, merging with integrity constraints, evaluation, and evaluative multiple revision. (shrink)

The model of major transitions in evolution devised by Maynard Smith and Szathmáry has exerted tremendous influence over evolutionary theorists. Although MTE has been criticized for inconsistently combining different types of event, its ongoing appeal lies in depicting hierarchical increases in complexity by means of evolutionary transitions in individuality. In this paper, we consider the implications of major evolutionary events overlooked by MTE and its ETI-oriented successors, specifically the biological oxygenation of Earth, and the acquisitions of mitochondria and plastids. By (...) reflecting on these missed events, we reveal a central philosophical disagreement over the explanatory goals of major transitions theory that has yet to be made explicit in the literature. We go on to argue that this philosophical disagreement is only reinforced by Szathmáry’s recent revisions of MTE in the form of MTE 2.0. This finding motivates us to propose an alternative explanatory strategy: specifically, an interactionist metabolic perspective on major transitions. A metabolic framework not only avoids many of the criticisms that beset classic and revised MTE models, but also accommodates missing events and provides crucial explanatory components for standard major transitions. Although we do not provide a full-blown alternative theory and do not claim to achieve unity, we explain why foregrounding metabolism is crucial for any attempt to capture the major turning points in evolution, and why it does not lead to unmanageable pluralism. (shrink)

The structuralist reconstruction of the metabolic biochemistry here presented is a more complete and revised version than the one presented in Donolo, Federico & Lorenzano (2006). This version, as the previous one, continues with the reconstructive task initiated by César Lorenzano (2002), but advances further on those elements which remained pendent of reconstruction: applications subsequent to the paradigmatic one, for being these “too diversified and numerous” (p. 210).In line with which is said before, the objective of this new reconstruction (...) is to make the theoretical network of the biochemistry wider, in order to be able to capture the many successful applications (paradigmatic examples or exemplars) which appear in modern university textbooks. In order to accomplish this, major conceptual precisions are being introduced which will have repercussions in a modification and increased complexity of the fundamental law implicit in the text books, but still conserving the previous basic idea. Because of all this we can say that the present article goes further into the reconstruction task of the metabolic biochemistry theory. (shrink)

The standard representation of the Central Dogma (CD) of Molecular Biology conspicuously ignores metabolism. However, both the metabolites and the biochemical fluxes behind any biological phenomenon are encrypted in the DNA sequence. Metabolism constrains and even changes the information flow when the DNA‐encoded instructions conflict with the homeostasis of the biochemical network. Inspection of adaptive virulence programs and emergence of xenobiotic‐biodegradation pathways in environmental bacteria suggest that their main evolutionary drive is the expansion of their metabolic networks towards new (...) chemical landscapes rather than perpetuation and spreading of their DNA sequences. Faulty enzymatic reactions on suboptimal substrates often produce reactive oxygen species (ROS), a process that fosters DNA diversification and ultimately couples catabolism of the new chemicals to growth. All this calls for a revision of the CD in which metabolism (rather than DNA) has the leading role. (shrink)

There is much discussion in the media and some of the scientific literature of how many of the conclusions from scientific research should be doubted. These critiques often focus on studies – typically in non‐experimental spheres of biomedical and social sciences – that search large datasets for novel correlations, with a risk that inappropriate statistical evaluations might yield dubious conclusions. By contrast, results from experimental biological research can often be interpreted largely without statistical analysis. Typically: novel observation(s) are reported, and (...) an explanatory hypothesis is offered; multiple labs undertake experiments to test the hypothesis; interpretation of the results may refute the hypothesis, support it or provoke its modification; the test/revise sequence is reiterated many times; and the field moves forward. I illustrate this experimental/non‐experimental dichotomy by examining the contrasting recent histories of: (a) our remarkable and growing understanding of how several inositol‐containing phospholipids contribute to the lives of eukaryote cells; and (b) the difficulty of achieving any agreed mechanistic understanding of why consuming dietary supplements of inositol is clinically beneficial in some metabolic diseases. (shrink)

Clinicians have a convention whereby symptoms are subjective statements 'as told by' patients, whereas signs are outwardly observable facts. Yet both first-person reports and third-person observations are theory laden and can bias conclusions. Two aspects of the oft-mentioned unreliability of reports are the subject's interpretation of them and the experimenter's assumptions when translating introspective reports into scientifically useful characterizations. Meticulous training of introspectors can address their mischief, whereas investigators can become more attentive to their own theory-laden biases. In the case (...) of hallucinations, for example, ignoring some customary third-person constructs and focusing on the visual experience itself has led to fresh explanations of visual symptoms based on cortical physiology rather than conceptual categories. Constructs that historically have ignored the subject's state of mind are also problematic; an example is the so-called resting state during metabolic brain imaging, long believed to reflect a blank mental slate. Introspective reports, not accepted literally but properly interpreted and revised by investigators as necessary, are legitimate sources of data. (shrink)

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and (...) [18F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control. (shrink)

According to the cognitive model of psychopathology, maladaptive beliefs about oneself, others, and the world are the main factors contributing to the development and persistence of various forms of mental suffering. Therefore, the key therapeutic process of Cognitive Behavioral Therapy (CBT)—a therapeutic approach rooted in the cognitive model—is cognitive restructuring, i.e., a process of revision of such maladaptive beliefs. In this paper, I examine the philosophical assumptions underlying CBT and offer theoretical reasons to think that the effectiveness of belief (...) revision in psychotherapy is very limited. This is the case, I argue, because the cognitive model wrongly assumes that our body of beliefs is unified, while it is in fact fragmented. (shrink)

The reprogramming of metabolism has been identified as one of the hallmarks of cancer. It is becoming more and more frequent to connect other diseases with metabolic reprogramming. This article aims to argue that metabolic reprogramming is not driven by disease but instead is the main hallmark of metabolism, based on its dynamic behavior that allows it to continuously adapt to changes in the internal and external conditions.

Belief revision (BR) and truthlikeness (TL) emerged independently as two research programmes in formal methodology in the 1970s. A natural way of connecting BR and TL is to ask under what conditions the revision of a belief system by new input information leads the system towards the truth. It turns out that, for the AGM model of belief revision, the only safe case is the expansion of true beliefs by true input, but this is not very interesting (...) or realistic as a model of theory change in science. The new accounts of non-prioritized belief revision do not seem more promising in this respect, and the alternative BR account of updating by imaging leads to other problems. Still, positive results about increasing truthlikeness by belief revision may be sought by restricting attention to special kinds of theories. Another approach is to link truthlikeness to epistemic matters by an estimation function which calculates expected degrees of truthlikeness relative to evidence. Then we can study how the expected truthlikeness of a theory changes when probabilities are revised by conditionalization or imaging. Again, we can ask under what conditions such changes lead our best theories towards the truth. (shrink)

Whipple disease is a rare, infectious, disease first described from a single case by Whipple in 1907. As well as characterising the clinical and pathological features of the condition, Whipple made two suggestions regarding its aetiology. These were either than the disease was caused by an infectious agent, or that it was of metabolic origin. As the disease is now thought to be caused by infection with the bacterium Tropheryma whipplei, historical reviews of the history of the disease typically (...) mention only the first of these suggestions. In this paper, we therefore revisit Whipple’s other theory. We argue that a diverse and often successful research programme was developed around this mechanism of disease causation which gave rise to many useful findings on the condition. In the later parts of this article, we then turn to discuss the surprising neglect of this period of Whipple disease research in the current literature, and conclude by offering a brief reconstruction of this early history suitable for use in a technical context. (shrink)

In the flowering of Red-Green Thought over the past two decades, metabolic rift thinking is surely one of its most colorful varieties. The metabolic rift has captured the imagination of critical environmental scholars, becoming a shorthand for capitalism’s troubled relations in the web of life. This article pursues an entwined critique and reconstruction: of metabolic rift thinking and the possibilities for a post-Cartesian perspective on historical change, the world-ecology conversation. Far from dismissing metabolic rift thinking, my (...) intention is to affirm its dialectical core. At stake is not merely the mode of explanation within environmental sociology. The impasse of metabolic rift thinking is suggestive of wider problems across the environmental social sciences, now confronted by a double challenge. One of course is the widespread—and reasonable—sense of urgency to evolve modes of thought appropriate to an era of deepening biospheric instability. The second is the widely recognized—but inadequately internalized—understanding that humans are part of nature. (shrink)

Metabolic systems are complicated and contain very large numbers of interacting reactions and many internal regulatory mechanisms. This does not prevent the genetic composition of an organism from influencing its behavior, however, nor does it preclude the possibility that some aspects of its behavior may be amenable to simple explanations.

This integrative volume proposes major revisions to the APA ethics code and works toward creating an ethics code applicable across psychology, psychiatry, and related mental health professions. Careful analysis identifies theoretical and structural deficits in the principles and standards comprising the existing APA code, corrects its ambiguities, and provides scientific and compare-contrast illustrations to address current and potential controversies arising from current gray areas. Proposed revisions are informed by the American Medical Association, Canadian Psychological Association, and international ethics codes, emphasizing (...) not only clearer language and diverse situations but also deeper conceptualizations of professional skills such as decision-making and client engagement. Ideally, the resulting universal code would be more inclusive of evolving ethical challenges in increasingly complex work environments and society. Included in the coverage: Comparison of the APA and CPA ethics codes. Proposing five core and five supplementary ethical principles and their sub-principles. Analyzing the APA's ethical standards toward revising the APA ethics code. Elucidating new standards, domains, sub-domains, and meta-principles. Culling lessons from the 2017 AMA medical ethics code. Examining ethical decision-making: fallacies/biases and models. Proposing new concepts, such as participatory ethics and psychological co-regulation. Giving concrete and practical recommendations toward revising the APA ethics code and creating a universal mental health ethics code. An exhaustive text that spans clinical, research, teaching, and education domains, Revising the APA Ethics Code is essential reading for ethics scholars, practitioners, and the APA administrative and ethics committee hierarchies. These real-world guidelines will help ensure that the mental health professions remain both modern and moral. (shrink)

In larger animals a considerable part of the total body mass (e.g. body water, dissolved substances, mineral and organic deposits) does not consume significant amounts of oxygen. These materials can be considered to form a metabolically inert infrastructure which mainly serves three functions: (1) structural support to the organism, (2) storage of nutrients (building material and energy stores) and (3) transport and distribution of these materials. Considering the transport and support function of the metabolically inert structures and their interconnections it (...) is likely that the infrastructure will basically show some tree-like, branching building plan. The weight of the metabolically inert infrastructure of an organism, can be given by bW/(c+W), in which W=body weight, b and c are constants. With increasing size the weight of the metabolic inert infrastructure increases disproportionably. Experimental data concerning basic metabolic rate (M) in relation to body weight (W) better fit the equation M=a W(1-bW)/(c+W), (a=constant) than the conventional power law. (shrink)

Many kinds of multifunctional regulatory proteins have been identified that perform distinct biochemical functions in the nucleus, the cytoplasm, or both. Here we describe the recent discovery by Hall et al. (2004)1 of a new type of multifunctional protein: a metabolic enzyme that doubles as a transcription factor. This enzyme, Arg5,6, functions as a catalytic enzyme in ornithine biosynthesis and also binds and regulates the promoters of nuclear and mitochondrial genes. It may also regulate precursor mRNA metabolism. We discuss (...) how proteins that serve as both metabolic enzymes and transcription factors might have evolved. BioEssays 27:467–471, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

I consider the case of the “simplest” living beings—bacteria—and examine how their embodied activity constitutes an organism/environment interaction, out of which emerges the possibility of learning from an environment. I suggest that this mutual co-emergence of organism and environment implies a panbiotic educational interaction that is at once the condition for, and achievement of, all living beings. Learning and being learned from are entangled in varied ways throughout the biosphere. Education is not an exclusively human project, it is part of (...) the ancient evolutionary process of elaborating and diversifying the relational possibilities inherent in metabolism that has brought forth our diverse and flourishing world.ed from context, “education” appears as a set of ways in which humans actively engage and take responsibility for the learning outcomes of relationships with each other. Insofar as we consider this distinction absolute rather than a performed construct to be assessed by its consequences, we blind ourselves to the educative dimension of other species as well as our many miseducative engagements with them. If learning processes are inherent and constitutive of ecological communities, education theorists should devote their pedagogical sensitivities and insights to the crucial challenge of developing educative sustainable human–nature relations. (shrink)

Lymphangiogenesis is an important developmental process that is critical to regulation of fluid homeostasis, immune surveillance and response as well as pathogenesis of a number of diseases, among them cancer, inflammation, and heart failure. Specification, formation, and maturation of lymphatic blood vessels involves an interplay between a series of events orchestrated by various transcription factors that determine expression of key genes involved in lymphangiogenesis. These are traditionally thought to be under control of several key growth factors including vascular growth factor‐C (...) (VEGF‐C) and fibroblast growth factors (FGFs). Recent insights into VEGF and FGF signaling point to their role in control of endothelial metabolic processes such as glycolysis and fatty acid oxidation that, in turn, play a major role in regulation of lymphangiogenesis. These advances have significantly increased our understanding of lymphatic biology and opened new therapeutic vistas. Here we review our current understanding of metabolic controls in the lymphatic vasculature. (shrink)

I offer a major reassessment of Foucault’s philosophico-historical account of the basic problems of modernity. I revise our understanding of Foucault by countering the influential misinterpretations proffered by his European interlocutors such as Habermas and Derrida. Central to Foucault’s account of modernity was his work on two crucial concept pairs: freedom/power and reason/madness. I argue against the view of Habermas and Derrida that Foucault understood modern power and reason as straightforwardly opposed to modern freedom and madness. I show that Foucault (...) held a much more complex view of these pairs, a view encapsulated in his term ‘reciprocal incompatibility’. By revising our interpretation of Foucault’s work on modernity in this way, we open the way to much more effective deployments of his critical apparatus. (shrink)

Here, we analyze how the set of nucleotides in the cell is equilibrated and how this generates simple rules that help the cell to organize itself via maintenance of a stable non‐equilibrium state. A major mechanism operating to achieve this state is thermodynamic buffering via high activities of equilibrating enzymes such as adenylate kinase. Under stable non‐equilibrium, the ratios of free and Mg‐bound adenylates, Mg2+ and membrane potentials are interdependent and can be computed. The adenylate status is balanced with the (...) levels of reduced and oxidized pyridine nucleotides through regulated uncoupling of the pyridine nucleotide pool from ATP production in mitochondria, and through oxidation of substrates non‐coupled to NAD+ reduction in peroxisomes. The set of adenylates and pyridine nucleotides constitutes a generalized cell energy status and determines rates of major metabolic fluxes. As the result, fluxes of energy and information become organized spatially and temporally, providing conditions for self‐maintenance of metabolism. (shrink)

Several authors have investigated the question of whether canonical logic-based accounts of belief revision, and especially the theory of AGM revision operators, are compatible with the dynamics of Bayesian conditioning. Here we show that Leitgeb's stability rule for acceptance, which has been offered as a possible solution to the Lottery paradox, allows to bridge AGM revision and Bayesian update: using the stability rule, we prove that AGM revision operators emerge from Bayesian conditioning by an application of (...) the principle of maximum entropy. In situations of information loss, or whenever the agent relies on a qualitative description of her information state - such as a plausibility ranking over hypotheses, or a belief set - the dynamics of AGM belief revision are compatible with Bayesian conditioning; indeed, through the maximum entropy principle, conditioning naturally generated AGM revision operators. This mitigates an impossibility theorem of Lin and Kelly for tracking Bayesian conditioning with AGM revision, and suggests an approach to the compatibility problem that highlights the information loss incurred by acceptance rules in passing from probabilistic to qualitative representations of beliefs. (shrink)

Computational approaches in systems biology have become a powerful tool for understanding the fundamental mechanisms of cellular metabolism and regulation. However, the interplay between the regulatory and the metabolic system is still poorly understood. In particular, there is a need for formal mathematical frameworks that allow analyzing metabolism together with dynamic enzyme resources and regulatory events. Here, we introduce a metabolic-regulatory network model that allows integrating metabolism with transcriptional regulation, macromolecule production and enzyme resources. Using this model, we (...) show that the dynamic interplay between these different cellular processes can be formalized by a hybrid automaton, combining continuous dynamics and discrete control. (shrink)

Amsterdam University Press is a leading publisher of academic books, journals and textbooks in the Humanities and Social Sciences. Our aim is to make current research available to scholars, students, innovators, and the general public. AUP stands for scholarly excellence, global presence, and engagement with the international academic community.

The definition of metabolic syndrome has been, and still is, extremely controversial. My purpose is not to give a solution to the associated debate but to argue that the controversy is at least partially due to the different ‘causal content’ of the various definitions: their theoretical validity and practical utility can be evaluated by reconstructing or making explicit the underlying causal structure. I will therefore propose to distinguish the alternative definitions according to the kinds of causal content they carry: (...) definitions grounded on associations, definitions presupposing a causal model built upon statistical associations, and definitions grounded on underlying mechanisms. I suggest that analysing definitions according to their causal content can be helpful in evaluating alternative definitions of some diseases. I want to show how the controversy over MetS suggests a distinction among three kinds of definitions based on how explicitly they characterise the syndrome in causal terms, and on the type of causality involved. I will call ‘type 1 definitions’ those definitions that are purely associative; ‘type 2 definitions’ the definitions based on statistical associations, plus generic medical and causal knowledge; and ‘type 3 definitions’ the definitions based on mechanisms. These kinds of definitions, although different, can be related to each other. A definition with more specific causal content may be useful in the evaluation of definitions characterised by a lower degree of causal specificity. Moreover, the identification of the type of causality involved is of help to constitute a good criterion for choosing among different definitions of a pathological entity. In section I introduce the controversy about MetS, in section I propose some remarks about medical definitions and their ‘causal import’, and in section I suggest that the different attitudes towards the definition of MetS are relevant to evaluate their explicative power. (shrink)

Belief revision theory studies how an ideal doxastic agent should revise her beliefs when she receives new information. In part I, I have first presented the AGM theory of belief revision. Then I have focused on the problem of iterated belief revisions. In part II, I will first present ranking theory (Spohn 1988). Then I will show how it solves the problem of iterated belief revisions. I will conclude by sketching two areas of future research.

Stewart and Korol (“De-Signing Fat,” International Journal of Applied Philosophy 23.2 [2009]) contend that obesity is benign. In support of their position they have focussed on selected papers that do not take into consideration key realities. Their attempt to minimise the impact of obesity appears to centre on how difficult it can be to lose weight by diet alone (and its risks) and problems with measurements of obesity, while failing to acknowledge the specific and well-documented impact of deleterious biochemical alterations (...) arising from central obesity. Stewart and Korol also do not point out the considerable controversy with the fat but fit (metabolically healthy obesity [MHO]) concept. Whether looping from above or below, nothing changes the biochemical realities of central obesity. Above all, Stewart and Korol never once mention the benefits of obesity prevention, rather focussing on the difficulties of losing weight. Thus, respectfully, a word of caution is put forward on the views of Stewart and Korol regarding obesity. (shrink)

This is a survey paper. Contents: 1 Introduction -- 2 The representation of belief -- 3 Kinds of belief change -- 4 Coherence constraints for belief revision -- 5 Different modes of belief change -- 6 Two strategies for characterizing rational changes of belief - 6.1 The postulates strategy - 6.2 The constructive strategy -- 7 An abstract view of the elements of belief change -- 8 Iterated changes of belief -- 9 Further developments - 9.1 Variants and extensions (...) of belief revision - 9.2 Updates - 9.3 Default inferences as expectation revision - 9.4 Belief merging -- 10 Concluding remarks. (shrink)

We present a general framework for representing belief-revision rules and use it to characterize Bayes's rule as a classical example and Jeffrey's rule as a non-classical one. In Jeffrey's rule, the input to a belief revision is not simply the information that some event has occurred, as in Bayes's rule, but a new assignment of probabilities to some events. Despite their differences, Bayes's and Jeffrey's rules can be characterized in terms of the same axioms: "responsiveness", which requires that (...) revised beliefs incorporate what has been learnt, and "conservativeness", which requires that beliefs on which the learnt input is "silent" do not change. To illustrate the use of non-Bayesian belief revision in economic theory, we sketch a simple decision-theoretic application. (shrink)

Evidence for the association of ‘soluble’ enzymes in vivo is extensive and compelling. These associations occur in all compartments of the cell of both prokaryotes and eukaryotes. Several factors present in vivo promote these associations among enzymes whose association in vitro is often too weak to detect. Several physiological advantages of the associated enzyme complexes can be identified, most (but not all) of which are the consequence of microcompartmentation of metabolites (substrate channeling). Substrate channeling of intermediates by either a ‘direct (...) transfer’ process or ‘proximity effects’ can occur. The latter mechanism does not require the special molecular features needed for the direct transfer mechanism and may, therefore, exist in more general situations in the cell. Criticisms of these views are discussed. We argue that these criticisms have been largely answered by experiment and theory in recent years. Studies on simple systems in vitro, nevertheless, contribute important insights concerning the more complex phenomena in vivo. (shrink)

Conceptual engineering is the practice of revising concepts to improve how people talk and think. Its ability to improve talk and thought ultimately hinges on the successful dissemination of desired conceptual changes. Unfortunately, the field has been slow to develop methods to directly test what barriers stand in the way of propagation and what methods will most effectively propagate desired conceptual change. In order to test such questions, this paper introduces the masked time-lagged method. The masked time-lagged method tests people's (...) conceptual understanding at two different points in time without their knowledge of being tested, allowing us to measure conceptual revision in action. Using a masked time-lagged design on a content internalist framework, we attempted to revise PLANET and DINOSAUR in online participants to match experts' concepts. We successfully revised PLANET but not DINOSAUR, demonstrating some of the difficulties conceptual engineers face. Nonetheless, this paper provides conceptual engineers, regardless of framework, with the tools to tackle questions related to implementation empirically and head-on. (shrink)

Develops a concept of revision, akin in spirit to AGM partial meet revision, but in which the postulate of 'success' may fail. The basic idea is to see such an operation as composite, with a pre-processor using a priori considerations to resolve the question of whether to revise, following which another operation revises in a manner that protects the a priori material.

We describe a model of iterated belief revision that extends the AGM theory of revision to account for the effect of a revision on the conditional beliefs of an agent. In particular, this model ensures that an agent makes as few changes as possible to the conditional component of its belief set. Adopting the Ramsey test, minimal conditional revision provides acceptance conditions for arbitrary right-nested conditionals. We show that problem of determining acceptance of any such nested (...) conditional can be reduced to acceptance tests for unnested conditionals. Thus, iterated revision can be accomplished in a "virtual" manner, using uniterated revision. (shrink)