The type-level abstraction is a formal way to represent molecular structures in biological practice. Graphical representations of molecular structures of biological objects are also used to identify functional processes of things. This paper will reveal that category theory is a formal mathematical language not only to visualize molecular structures of biological objects as type-level abstraction formally but also to understand how to infer biological functions from the molecular structures of biological objects. Category theory is a toolkit (...) to understand biological knowledge at the type-level formally, not individual token-level, as well as typical heuristic strategies in molecular biology. (shrink)

In this paper, I defend the agent/patient distinction against critics who argue that causal interactions are symmetrical. Specifically, I argue that there is a widespread type of causal interaction between distinct entities, resulting in a type of ontological asymmetry that provides principled grounds for distinguishing agents from patients. The type of interaction where the asymmetry is found is when one of the entities undergoes a change in kind, structure, powers, or intrinsic properties as a result of the interaction while the (...) other does not. Interactions of this type are widespread in molecular biology and chemistry. I focus specifically on (i) the actions of enzymes on substrates and (ii) water molecules breaking the bonds of polarized molecules. Finally, I respond to objections by laying out and to a limited extent defending three commitments of my account: emergent entities and powers, realism about chemical kinds or structures, and the assumption of the agent/patient distinction in functional attributions in biology. (shrink)

The Aristotelian axiom that function follows form was beautifully instantiated in molecular biology by the discovery of DNA’s structure that immediately suggested how DNA might work as depository and vehicle for genetic information. However, later on molecular biology became infatuated with the gene that became the center of the universe. This gene-centered viewpoint is an obstacle for the emerging field of evo-devo aiming at finding the causal connections between evolution and biological development. Here it is argued that (...) class='Hi'>molecular biology must reject the narrow-minded causality associated with the gene-centered view and so it must recover to the spirit of Aristotelian natural history and its four types of causation in order to foster the evo-devo field of research. (shrink)

I consider three explanatory strategies from recent systems biology that are driven by mathematics as much as mechanistic detail. Analysis of differential equations drives the first strategy; topological analysis of network motifs drives the second; mathematical theorems from control engineering drive the third. I also distinguish three abstraction types: aggregations, which simplify by condensing information; generalizations, which simplify by generalizing information; and structurations, which simplify by contextualizing information. Using a common explanandum as reference point—namely, the robust perfect adaptation of chemotaxis (...) in Escherichia coli—I argue that each strategy invokes a different combination of abstraction types and that each targets its abstractions to different mechanistic details. (shrink)

Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

We characterize a type of functional explanation that addresses why a homologous trait originating deep in the evolutionary history of a group remains widespread and largely unchanged across the group’s lineages. We argue that biologists regularly provide this type of explanation when they attribute conserved functions to phenotypic and genetic traits. The concept of conserved function applies broadly to many biological domains, and we illustrate its importance using examples of molecular sequence alignments at the intersection of evolution and cell (...) biology. We use these examples to show how the study of conserved functions can integrate knowledge of a trait’s causal effects on fitness and its history of natural selection without invoking adaptation. We also show how conserved function provides a novel basis for addressing objections against evolutionary functions raised by Robert Cummins. (shrink)

It is arguably the case that olfactory system contains two senses that share the same type of stimuli, sensory transduction mechanism, and processing centers. Yet, orthonasal and retronasal olfaction differ in their types of perceptible objects as individuated by their sensory qualities. What will be explored in this paper is how the account of orthonasal smell developed in the Molecular Structure Theory of smell can be expanded for retronasal olfaction (Young, 2016, 2019a-b, 2020). By considering the object of olfactory (...) perception to be the molecular structure of chemical compounds composing odor plumes, Molecular Structure Theory provides a means for determining an odor’s olfactory quality, how odors can be identified and individuated, and how we perceive smellscapes. Surveying the differences between orthonasal and retronasal olfaction provides the basis for the central argument of the paper that the perceptible objects we refer to as smells and individuated on the basis of their olfactory qualities are only relative to orthonasal olfaction. Retronasal olfaction it is speculatively concluded might play an essential role in our perception of flavorful objects. (shrink)

In current philosophical discussions on evidence in the medical sciences, epidemiology has been used to exemplify a specific version of evidential pluralism. According to this view, known as the Russo–Williamson Thesis, evidence of both difference-making and mechanisms is produced to make causal claims in the health sciences. In this paper, I present an analysis of data and evidence in epidemiological practice, with a special focus on research on the exposome, and I cast doubt on the extent to which evidential pluralism (...) holds in this case. I start by focusing on the claim that molecular data allows for the production of mechanistic evidence. On the basis of a close look at the ways in which molecular data is used in exposome research, I caution against interpretations in terms of mechanistic evidence. Secondly, I expand my critical remarks on the thesis by addressing the conditions under which data is categorised as evidence in exposome research. I argue that these show that the classification of a dataset as a type of evidence is dependent on the ways in which the data is used. This is in contrast with the approach of evidential pluralism, where evidence is classified in different types on the basis of its intrinsic properties. Finally, I come back to what I consider the core of the thesis and suggest that the epidemiological research analysed in the paper indicates different interpretations of evidential pluralism and its applicability in the health sciences. (shrink)

In some recent papers (G. ‘t Hooft and others), it has been argued that quantum mechanics can arise from classical cellular automata. Nonetheless, G. Shpenkov has proved that the classical wave equation makes it possible to derive a periodic table of elements, which is very close to Mendeleyev’s one, and describe also other phenomena related to the structure of molecules. Hence the classical wave equation complements Schrödinger’s equation, which implies the appearance of a cellular automaton molecular model starting from (...) classical wave equation. The other studies show that the microworld is constituted as a tessellation of primary topological balls. The tessellattice becomes the origin of a submicrospic mechanics in which a quantum system is subdivided to two subsystems: the particle and its inerton cloud, which appears due to the interaction of the moving particle with oncoming cells of the tessellattice. The particle and its inerton cloud periodically change the momentum and hence move like a wave. The new approach allows us to correlate the Klein-Gordon equation with the deformation coat that is formed in the tessellatice around the particle. The submicroscopic approach shows that the source of any type of wave movements including the Klein-Gordon, Schrödinger, and classical wave equations is hidden in the tessellattice and its basic exciations – inertons, carriers of mass and inert properies of matter. We also discuss possible correspondence with Konrad Zuse’s calculating space. (shrink)

Systems biologists often distance themselves from reductionist approaches and formulate their aim as understanding living systems “as a whole.” Yet, it is often unclear what kind of reductionism they have in mind, and in what sense their methodologies would offer a superior approach. To address these questions, we distinguish between two types of reductionism which we call “modular reductionism” and “bottom-up reductionism.” Much knowledge in molecular biology has been gained by decomposing living systems into functional modules or through detailed (...) studies of molecular processes. We ask whether systems biology provides novel ways to recompose these findings in the context of the system as a whole via computational simulations. As an example of computational integration of modules, we analyze the first whole-cell model of the bacterium M. genitalium. Secondly, we examine the attempt to recompose processes across different spatial scales via multi-scale cardiac models. Although these models rely on a number of idealizations and simplifying assumptions as well, we argue that they provide insight into the limitations of reductionist approaches. Whole-cell models can be used to discover properties arising at the interfaces of dynamically coupled processes within a biological system, thereby making more apparent what is lost through decomposition. Similarly, multi-scale modeling highlights the relevance of macroscale parameters and models and challenges the view that living systems can be understood “bottom-up.” Specifically, we point out that system-level properties constrain lower-scale processes. Thus, large-scale modeling reveals how living systems at the same time are more and less than the sum of the parts. (shrink)

The brain is composed of electrically excitable neuronal networks regulated by the activity of voltage-gated ion channels. Further portraying the molecular composition of the brain, however, will not reveal anything remotely reminiscent of a feeling, a sensation or a conscious experience. In classical physics, addressing the mind–brain problem is a formidable task because no physical mechanism is able to explain how the brain generates the unobservable, inner psychological world of conscious experiences and how in turn those conscious experiences steer (...) the underlying brain processes toward desired behavior. Yet, this setback does not establish that consciousness is non-physical. Modern quantum physics affirms the interplay between two types of physical entities in Hilbert space: unobservable quantum states, which are vectors describing what exists in the physical world, and quantum observables, which are operators describing what can be observed in quantum measurements. Quantum no-go theorems further provide a framework for studying quantum brain dynamics, which has to be governed by a physically admissible Hamiltonian. Comprising consciousness of unobservable quantum information integrated in quantum brain states explains the origin of the inner privacy of conscious experiences and revisits the dynamic timescale of conscious processes to picosecond conformational transitions of neural biomolecules. The observable brain is then an objective construction created from classical bits of information, which are bound by Holevo’s theorem, and obtained through the measurement of quantum brain observables. Thus, quantum information theory clarifies the distinction between the unobservable mind and the observable brain, and supports a solid physical foundation for consciousness research. (shrink)

According to a chorus of authors, the human life-world is currently invaded by an avalanche of high-tech devices referred to as “emerging,” ”intimate,” or ”NBIC” technologies: a new type of contrivances or gadgets designed to optimize cognitive or sensory performance and / or to enable mood management. Rather than manipulating objects in the outside world, they are designed to influence human bodies and brains more directly, and on a molecular scale. In this paper, these devices will be framed as (...) ‘extimate’ technologies (both intimate and external; both embedded and foreign; both life-enhancing and intrusive), a concept borrowed from Jacques Lacan. Although Lacan is not commonly regarded as a philosopher of technology, the dialectical relationship between human desire and technological artefacts runs as an important thread through his work. Moreover, he was remarkably prescient concerning the blending of life science and computer science, which is such a distinctive feature of the current techno-scientific turn. Building on a series of Lacanian concepts, my aim is to develop a psychoanalytical diagnostic of the technological present. Finally, I will indicate how such an analysis may inform our understanding of human life and embodiment as such. (shrink)

Background: Ontologies and taxonomies are among the most important computational resources for molecular biology and bioinformatics. A series of recent papers has shown that the Gene Ontology (GO), the most prominent taxonomic resource in these fields, is marked by flaws of certain characteristic types, which flow from a failure to address basic ontological principles. As yet, no methods have been proposed which would allow ontology curators to pinpoint flawed terms or definitions in ontologies in a systematic way. Results: We (...) present computational methods that automatically identify terms and definitions which are defined in a circular or unintelligible way. We further demonstrate the potential of these methods by applying them to isolate a subset of 6001 problematic GO terms. By automatically aligning GO with other ontologies and taxonomies we were able to propose alternative synonyms and definitions for some of these problematic terms. This allows us to demonstrate that these other resources do not contain definitions superior to those supplied by GO. Conclusion: Our methods provide reliable indications of the quality of terms and definitions in ontologies and taxonomies. Further, they are well suited to assist ontology curators in drawing their attention to those terms that are ill-defined. We have further shown the limitations of ontology mapping and alignment in assisting ontology curators in rectifying problems, thus pointing to the need for manual curation. (shrink)

This paper addresses the cultural impact of genomics and the Human Genome Project on human self-understanding. Notably, it addresses the claim made by Francis Collins that the genome is the language of God and the claim made by Max Delbrück that Aristotle must be credited with having predicted DNA as the soul that organises bio-matter. From a continental philosophical perspective I will argue that human existence results from a dialectical interaction between two types of texts: the language of molecular (...) biology and the language of civilisation; the language of the genome and the language of our socio-cultural, symbolic ambiance. Whereas the former ultimately builds on the alphabets of genes and nucleotides, the latter is informed by primordial texts such as the Bible and the Quran. In applied bioethics deliberations on genomics, science is easily framed as liberating and progressive, religious world-views as conservative an... (shrink)

Vaccine research, as well as the development, testing, clinical trials, and commercial uses of vaccines involve complex processes with various biological data that include gene and protein expression, analysis of molecular and cellular interactions, study of tissue and whole body responses, and extensive epidemiological modeling. Although many data resources are available to meet different aspects of vaccine needs, it remains a challenge how we are to standardize vaccine annotation, integrate data about varied vaccine types and resources, and support advanced (...) vaccine data analysis and inference. To address these problems, the community-based Vaccine Ontology (VO) has been developed through collaboration with vaccine researchers and many national and international centers and programs, including the National Center for Biomedical Ontology (NCBO), the Infectious Disease Ontology (IDO) Initiative, and the Ontology for Biomedical Investigations (OBI). VO utilizes the Basic Formal Ontology (BFO) as the top ontology and the Relation Ontology (RO) for definition of term relationships. VO is represented in the Web Ontology Language (OWL) and edited using the Protégé-OWL. Currently VO contains more than 2000 terms and relationships. VO emphasizes on classification of vaccines and vaccine components, vaccine quality and phenotypes, and host immune response to vaccines. These reflect different aspects of vaccine composition and biology and can thus be used to model individual vaccines. More than 200 licensed vaccines and many vaccine candidates in research or clinical trials have been modeled in VO. VO is being used for vaccine literature mining through collaboration with the National Center for Integrative Biomedical Informatics (NCIBI). Multiple VO applications will be presented. (shrink)

The neutral theory often is presented as a theory of "noise" or silent changes at an isolated "molecular level", relevant to marking the steady pace of divergence, but not to the origin of biological structure, function, or complexity. Nevertheless, precisely these issues can be addressed in neutral models, such as those elaborated here in regard to scrambled ciliate genes, gRNA-mediated RNA editing, the transition from self-splicing to spliceosomal splicing, and the retention of duplicate genes. All of these are instances (...) of a more general scheme of "constructive neutral evolution" that invokes biased variation, epistatic interactions, and excess capacities to account for a complex series of steps giving rise to novel structures or operations. The directional and constructive outcomes of these models are not due to neutral allele fixations per se, but to these other factors. Neutral models of this type may help to clarify the poorly understood role of non-selective factors in evolutionary innovation and directionality. (shrink)

In this paper it is argued that the multiple realizability argument and Kripke's argument are based on schemas of identifications rather than identification. In fact, "heat = molecular motion" includes a term "molecular motion" that does not capture a natural kind, nor has a unique referent. If properly framed, this schema suits also for the type identity theory of mind. Some consequences of this point are evaluated.

The introductory personal remarks refer to my motivations for choosing research projects, and for moving from physics to molecular biology and then to development, with Hydra as a model system. Historically, Trembley’s discovery of Hydra regeneration in 1744 was the begin¬ning of developmental biology as we understand it, with passionate debates about preformation versus de novo generation, mechanisms versus organisms. In fact, seemingly conflicting bottom-up and top-down concepts are both required in combination to understand development. In modern terms, this (...) means analysing the molecules involved, as well as searching for physical principles underlying development within systems of molecules, cells and tissues. During the last decade, molecular biology has provided surprising and impressive evidence that the same types of mol¬ecules and molecular systems are involved in pattern formation in a wide range of organisms, including coelenterates like Hydra, and thus appear to have been “invented” early in evolution. Likewise, the features of certain systems, especially those of developmental regulation, are found in many different organisms. This includes the generation of spatial structures by the interplay of self-enhancing activation and “lateral” inhibitory effects of wider range, which is a main topic of my essay. Hydra regeneration is a particularly clear model for the formation of defined patterns within initially near-uniform tissues. In conclusion, this essay emphasizes the analysis of development in terms of physical laws, including the application of mathematics, and insists that Hydra was, and will continue to be, a rewarding model for understanding general features of embryogenesis and regeneration. -/- -/- . (shrink)

Within the sedimentation diagram of infective RNA preparations isolated from Tobacco Mosaic Virus, undegraded molecules form a sharp peak with a molecular weight corresponding to the total RNA content of the virus particle. Degradation kinetics by ribonuclease is of the linear, single-target type, indicating that the RNA is single-stranded. The intact RNA of a virus particle thus forms one big single-stranded molecule. Quantitative evaluation of the effect degradation by RNA-ase on the infectivity of the RNA shows that the integrity (...) of the entire molecule is required for its biological activity. (shrink)

In this paper we extend Neutro-Algebra and Anti-Algebra to geometric spaces, founding Neutro/Geometry and AntiGeometry. While Non-Euclidean Geometries resulted from the total negation of a specific axiom (Euclid's Fifth Postulate), AntiGeometry results from the total negation of any axiom or even more axioms of any geometric axiomatic system (Euclidean, Hilbert, etc. ) and of any type of geometry such as Geometry (Euclidean, Projective, Finite, Differential, Algebraic, Complex, Discrete, Computational, Molecular, Convex, etc.), and Neutro-Geometry results from the partial negation of (...) one or more axioms [and without total negation of any axiom] of any geometric axiomatic system and of any type of geometry. Generally, instead of a classical geometric Axiom, one can take any classical geometric Theorem of any axiomatic system and of any type of geometry, and transform it by Neutrosophication or Antisofication into a Neutro-Theorem or Anti-Theorem respectively to construct a Neutro-Geometry or Anti-Geometry. Therefore, Neutro-Geometry and Anti-Geometry are respectively alternatives and generalizations of Non-Euclidean Geometries. In the second part, the evolution from Paradoxism to Neutrosophy, then to NeutroAlgebra and Anti-Algebra, then to Neutro-Geometry and Anti-Geometry, and in general to Neutro-Structure and Anti-Structure that arise naturally in any field of knowledge is recalled. At the end, applications of many Neutro-Structures in our real world are presented. (shrink)

In this paper we extend the NeutroAlgebra & AntiAlgebra to the geometric spaces, by founding the NeutroGeometry & AntiGeometry. While the Non-Euclidean Geometries resulted from the total negation of one specific axiom (Euclid’s Fifth Postulate), the AntiGeometry results from the total negation of any axiom or even of more axioms from any geometric axiomatic system (Euclid’s, Hilbert’s, etc.) and from any type of geometry such as (Euclidean, Projective, Finite, Affine, Differential, Algebraic, Complex, Discrete, Computational, Molecular, Convex, etc.) Geometry, and (...) the NeutroGeometry results from the partial negation of one or more axioms [and no total negation of no axiom] from any geometric axiomatic system and from any type of geometry. Generally, instead of a classical geometric Axiom, one may take any classical geometric Theorem from any axiomatic system and from any type of geometry, and transform it by NeutroSophication or AntiSophication into a NeutroTheorem or AntiTheorem respectively in order to construct a NeutroGeometry or AntiGeometry. Therefore, the NeutroGeometry and AntiGeometry are respectively alternatives and generalizations of the Non-Euclidean Geometries. In the second part, we recall the evolution from Paradoxism to Neutrosophy, then to NeutroAlgebra & AntiAlgebra, afterwards to NeutroGeometry & AntiGeometry, and in general to NeutroStructure & AntiStructure that naturally arise in any field of knowledge. At the end, we present applications of many NeutroStructures in our real world. (shrink)

Biochemical networks are often called upon to illustrate emergent properties of living systems. In this contribution, I question such emergentist claims by means of theoretical work on genetic regulatory models and random Boolean networks. If the existence of a critical connectivity Kc of such networks has often been coined “emergent” or “irreducible”, I propose on the contrary that the existence of a critical connectivity Kc is indeed mathematically explainable in network theory. This conclusion also applies to many other types of (...) formal networks and weakens the emergentist claim attached to bio-molecular networks, and by extension to living systems. (shrink)

Natural systems are categorized according to their structural and dynamical similarities. A two-dimensional schema is proposed as a kind of "periodic table" of natural systems. Six of eight levels in this schema serve as sources of analogies, two levels are the targets of analogical reasoning. The source domains are the atomic, molecular, macromolecular, micro-organismic, organismic and socio-cultural systems and processes. One of the target domains discussed in the article is the level of subatomic particles. The other target domain, not (...) discussed in the article, could be the level of future supra-national systems. Three types of processes are identified occurring in natural systems: conservation, modification and transformation. Modifications allow a reversible adaptation of a system to environmental influences by changing its internal state. The entirety of all internal states defines the "state space" of the system. Similarities of state spaces between systems of six levels are investigated. A dual-space picture of natural systems can be defined on six levels, the source domains of analogical reasoning. On the subatomic level, space-time is identified as part of the state space of subatomic particles. However, space-time needs a completion by an additional state space in order to obtain a dual-space picture also for subatomic particles. A "basic space" is proposed, so that subatomic particles exist simultaneously in space-time and in basic space. The basic space is assumed to be a circular space, where masses and charges circulate force-free and generate the spin and the magnetic moment of particles. A presumption about the existence of hypothetical matter not detectable in space-time is derived. Such primitive forms of matter could exist in basic space only and represent the dark matter. (shrink)

The term “Complex Systems Biology” was introduced a few years ago [Kaneko, 2006] and, although not yet of widespread use, it seems particularly well suited to indicate an approach to biology which is well rooted in complex systems science. Although broad generalizations are always dangerous, it is safe to state that mainstream biology has been largely dominated by a gene-centric view in the last decades, due to the success of molecular biology. So the one gene - one trait approch, (...) which has often proved to be effective, has been extended to cover even complex traits. This simplifying view has been appropriately criticized, and the movement called systems biology has taken off. Systems biology [Noble, 2006] emphasizes the presence of several feedback loops in biological systems, which severely limit the range of validity of explanations based upon linear causal chains (e.g. gene → behaviour). Mathematical modelling is one the favourite tools of systems biologists to analyze the possible effects of competing negative and positive feedback loops which can be observed at several levels (from molecules to organelles, cells, tissues, organs, organisms, ecosystems). Systems biology is by now a well-established field, as it can be inferred by the rapid growth in number of conferences and journals devoted to it, as well as by the existence of several grants and funded projects.Systems biology is mainly focused upon the description of specific biological items, like for example specific organisms, or specific organs in a class of animals, or specific genetic-metabolic circuits. It therefore leaves open the issue of the search for general principles of biological organization, which apply to all living beings or to at least to broad classes. We know indeed that there are some principles of this kind, biological evolution being the most famous one. The theory of cellular organization also qualifies as a general principle. But the main focus of biological research has been that of studying specific cases, with some reluctance to accept (and perhaps a limited interest for) broad generalizations. This may however change, and this is indeed the challenge of complex systems biology: looking for general principles in biological systems, in the spirit of complex systems science which searches for similar features and behaviours in various kinds of systems. The hope to find such general principles appears well founded, and I will show in Section 2 that there are indeed data which provide support to this claim. Besides data, there are also general ideas and models concerning the way in which biological systems work. The strategy, in this case, is that of introducing simplified models of biological organisms or processes, and to look for their generic properties: this term, borrowed from statistical physics, is used for those properties which are shared by a wide class of systems. In order to model these properties, the most effective approach has been so far that of using ensembles of systems, where each member can be different from another one, and to look for those properties which are widespread. This approach was introduced many years ago [Kauffman, 1971] in modelling gene regulatory networks. At that time one had very few information about the way in which the expression of a given gene affects that of other genes, apart from the fact that this influence is real and can be studied in few selected cases (like e.g. the lactose metabolism in E. coli). Today, after many years of triumphs of molecular biology, much more has been discovered, however the possibility of describing a complete map of gene-gene interactions in a moderately complex organism is still out of reach. Therefore the goal of fully describing a network of interacting genes in a real organism could not be (and still cannot be) achieved. But a different approach has proven very fruitful, that of asking what are the typical properties of such a set of interacting genes. Making some plausible hypotheses and introducing some simplifying assumptions, Kauffman was able to address some important problems. In particular, he drew attention to the fact that a dynamical system of interacting genes displays selforganizing properties which explain some key aspects of life, most notably the existence of a limited number of cellular types in every multicellular organism (these numbers are of the order of a few hundreds, while the number of theoretically possible types, absent interactions, would be much much larger than the number of protons in the universe). In section 3 I will describe the ensemble based approach in the context of gene regulatory networks, and I will show that it can describe some important experimental data. Finally, in section 4 I will discuss some methodological aspects. (shrink)

Without directly addressing the Demarcation Problem for logic—the problem of distinguishing logical vocabulary from others—we focus on distinctive aspects of logical vocabulary in pursuit of a second goal in the philosophy of logic, namely, proposing criteria for the justification of logical rules. Our preferred approach has three components. Two of these are effectively Belnap’s, but with a twist. We agree with Belnap’s response to Prior’s challenge to inferentialist characterisations of the meanings of logical constants. Belnap argued that for a logical (...) constant to exist, its rules must be conservative over a previously given consequence relation and guarantee the uniqueness of the constant. The twist is that we require logical vocabulary to be provably conservative, not over a previously given formal consequence relation, but over a previously given meaningful vocabulary of a language. Uniqueness is also a feature defined in terms of provability: if two syntactically distinguished expressions are governed by the same rules, then formulas with them as main operators are interderivable. Belnap’s criteria are not only those for the existence of a logical constant, but more: they are what distinguishes logical vocabulary from all other expressions. It is the defining mark of a logical constant that it is provably conservative over the fragment of the language which excludes it and that its rules guarantee its uniqueness. The third component is the topic neutrality of logic. The provable conservativeness of logic over a previously given vocabulary of a language is motivated, in part, by appeal to molecularism in the theory of meaning. Molecularity is a feature endorsed by the theory of meaning as a whole, so it does not distinguish logical constants from other expressions. The same is true for conservativeness. We argue that molecularity, and hence conservativeness, are implicit presuppositions of speakers’ use of language: the addition of new vocabulary to a language is presupposed to be conservative. But this presupposition is one that we should be able reflectively to endorse (such as when attempting a rational reconstruction of the use of the vocabulary). Thus, where conservativeness is found to fail, this defect should be remedied and the use of the vocabulary corrected (as in classical negation) or excised altogether (as in pejoratives). We go on to characterise a notion of topic neutrality, which we argue applies to logical vocabulary. We then note that reflective endorsement of the conservativeness of a topic neutral vocabulary requires a proof that the vocabulary is conservative relative to any base vocabulary. Thus we require that logical vocabulary be demonstrably conservative. Allying this requirement, distinctive of logic, to a general consideration about the commitments of assertion yields a mode of justification for logical constants akin to some conceptions of Harmony, i.e., to the idea that the consequences of assertion of a logical complex need to be warranted by the grounds and ought to be the strongest consequences warranted by the grounds. Intuitionistic logic acquires a somewhat familiar justification but emanating from a new motivation. (shrink)

Higher-order logic, with its type-theoretic apparatus known as the simple theory of types (STT), has increasingly come to be employed in theorizing about properties, relations, and states of affairs—or ‘intensional entities’ for short. This paper argues against this employment of STT and offers an alternative: ordinal type theory (OTT). Very roughly, STT and OTT can be regarded as complementary simplifications of the ‘ramified theory of types’ outlined in the Introduction to Principia Mathematica (on a realist reading). While STT, understood as (...) a theory of intensional entities, retains the Fregean division of properties and relations into a multiplicity of categories according to their adicities and ‘input types’ and discards the division of intensional entities into different ‘orders’, OTT takes the opposite approach: it retains the hierarchy of orders (though with some modifications) and discards the categorisation of properties and relations according to their adicities and input types. In contrast to STT, this latter approach avoids intensional counterparts of the Epimenides and related paradoxes. Fundamental intensional entities lie at the base of the proposed hierarchy and are also given a prominent part to play in the individuation of non-fundamental intensional entities. (shrink)

There is consensus within the chemosciences that olfactory perception is of the molecular structure of chemical compounds, yet within philosophical theories of smell there is little agreement about the nature of smell. The paper critically assesses the current state of debate regarding smells within philosophy in the hopes of setting it upon firm scientific footing. The theories to be covered are: Naïve Realism, Hedonic Theories, Process Theory, Odor Theories, and non-Objectivist Theories. The aforementioned theories will be evaluated based on (...) their explanations of the (a) the olfactory quality of a smell, (b) smells as distal entities, and (c) our experience of smells as intentional objects. The paper concludes with a defense of Molecular Structure Theory that demonstrating its superiority in accounting for each of these three aspects of smell. (shrink)

Recent debates in metaphysics have highlighted the significance of type theories, such as Simple Type Theory (STT), for our philosophical analysis. In this chapter, I present the salient features of a constructive type theory in the style of Martin-Löf, termed CTT. My principal aim is to convey the flavour of this rich, flexible and sophisticated theory and compare it with STT. I especially focus on the forms of quantification which are available in CTT. A further aim is to argue that (...) a comparison between a plurality of theories is beneficial to the philosophical analysis. We may, for example, discover helpful features of one theory that we may want to import into another context, thus enriching our repertoire of formal tools. Or, through comparison with a less well-known theory, we may gain a better understanding of the characteristics of the theories we are familiar with. As argued in this chapter, CTT has much to offer in all of these respects. (shrink)

This essay considers how scholarly approaches to the development of molecular biology have too often narrowed the historical aperture to genes, overlooking the ways in which other objects and processes contributed to the molecularization of life. From structural and dynamic studies of biomolecules to cellular membranes and organelles to metabolism and nutrition, new work by historians, philosophers, and STS scholars of the life sciences has revitalized older issues, such as the relationship of life to matter, or of physicochemical inquiries (...) to biology. This scholarship points to a novel molecular vista that opens up a pluralist view of molecularizations in the twentieth century and considers their relevance to current science. (shrink)

Whether or not quantum physics can account for molecular structure is a matter of considerable controversy. Three of the problems raised in this regard are the problems of molecular structure. We argue that these problems are just special cases of the measurement problem of quantum mechanics: insofar as the measurement problem is solved, the problems of molecular structure are resolved as well. In addition, we explore one consequence of our argument: that claims about the reduction or emergence (...) of molecular structure cannot be settled independently of the choice of a particular resolution to the measurement problem. Specifically, we consider how three standard putative solutions to the measurement problem inform our under- standing of a molecule in isolation, as well as of chemistry’s relation to quantum physics. (shrink)

Statements about the behavior of biochemical entities (e.g., about the interaction between two proteins) abound in the literature on molecular biology and are increasingly becoming the targets of information extraction and text mining techniques. We show that an accurate analysis of the semantics of such statements reveals a number of ambiguities that have to be taken into account in the practice of biomedical ontology engineering: Such statements can not only be understood as event reporting statements, but also as ascriptions (...) of dispositions or tendencies that may or may not refer to collectives of interacting molecules or even to collectives of interaction events. (shrink)

Molecular biology is a relatively new and very successful branch of science but currently it faces challenges posed by very complex issues that cannot be addressed by a traditional reductionist approach. However, despite its origins in the providential shift of some theoretical physicists to biology, currently molecular biology is immersed in a blind trend in which high-throughput technology, able to generate trillions of data, is becoming the leading edge of a discipline that has traded rational and critical thinking (...) for computer power, data crunching and statistics in hope of finding, once more, its way. However, the complex questions facing MB may only be solved by a paradigm shift in the causal way of thinking, so that complex, emergent, non-linear phenomena may be effectively understood in top-down and not in bottom-up terms. (shrink)

One of the most plausible and widely discussed examples of strong emergence is molecular structure. The only detailed account of it, which has been very influential, is due to Robin Hendry and is formulated in terms of downward causation. This paper explains Hendry’s account of the strong emergence of molecular structure and argues that it is coherent only if one assumes a diachronic reflexive notion of downward causation. However, in the context of this notion of downward causation, the (...) strong emergence of molecular structure faces three challenges that have not been met and which have so far remained unnoticed. First, the putative empirical evidence presented for the strong emergence of molecular structure equally undermines supervenience, which is one of the main tenets of strong emergence. Secondly, it is ambiguous how the assumption of determinate nuclear positions is invoked for the support of strong emergence, as the role of this assumption in Hendry’s argument can be interpreted in more than one way. Lastly, there are understandings of causation which render the postulation of a downward causal relation between a molecule’s structure and its quantum mechanical entities, untenable. (shrink)

In this paper I propose to describe, in brief, a semiotic paradigm which results from the redefinition of the linguistic sign as a molecular sememe. Borrowing a tactic from Wittgenstein, I wish to use the game of chess as an analogy for the sake of describing what a molecular sememe is. Then I hope to use it further to sketch several implications of this semiotic paradigm for literary criticism and critical theory.

”It is often assumed that knowledge claims must be justified. But what kind of justification is required for knowledge ? . . . ” (*) -/- presupposition: the kind of epistemic justification depends on the type of the knowledge claim and its respective knowledge claim tradeoff ’vague vs. precise’. -/- procedere: in two - almost purely logical - case studies I account for this tradeoff and question in each case what (if any) were its general outcome wrt justification -/- first (...) for basic measurement statements of the form ′′ϕ(x) = r ∈ IR ± δ′′ (wrt ”measurement accuracy realism” debate) -/- and secondly predication statements of the form ′′x is ( a case of )P′′ (wrt ”epistemic vagueness” debate). (shrink)

Today, the lipid bilayer structure is nearly ubiquitous, taken for granted in even the most rudimentary introductions to cell biology. Yet the image of the lipid bilayer, built out of lipids with heads and tails, went from having obscure origins deep in colloid chemical theory in 1924 to being “obvious to any competent physical chemist” by 1935. This chapter examines how this schematic, strictly heuristic explanation of the idea of molecular orientation was developed within colloid physical chemistry, and how (...) the image was transformed into a reflection of the reality and agency of lipid molecules in the biological microworld. Whereas in physical and colloid chemistry these images considered secondary to instrumental measurement and mathematical modeling of surface phenomena, in biology the manipulable image of the lipid on paper became an essential tool for the molecularization of the cell. (shrink)

The inflation of Type I error rates is thought to be one of the causes of the replication crisis. Questionable research practices such as p-hacking are thought to inflate Type I error rates above their nominal level, leading to unexpectedly high levels of false positives in the literature and, consequently, unexpectedly low replication rates. In this article, I offer an alternative view. I argue that questionable and other research practices do not usually inflate relevant Type I error rates. I begin (...) with an introduction to Type I error rates that distinguishes them from theoretical errors. I then illustrate my argument with respect to model misspecification, multiple testing, selective inference, forking paths, exploratory analyses, p-hacking, optional stopping, double dipping, and HARKing. In each case, I demonstrate that relevant Type I error rates are not usually inflated above their nominal level, and in the rare cases that they are, the inflation is easily identified and resolved. I conclude that the replication crisis may be explained, at least in part, by researchers’ misinterpretation of statistical errors and their underestimation of theoretical errors. (shrink)

The replication crisis has caused researchers to distinguish between exact replications, which duplicate all aspects of a study that could potentially affect the results, and direct replications, which duplicate only those aspects of the study that are thought to be theoretically essential to reproduce the original effect. The replication crisis has also prompted researchers to think more carefully about the possibility of making Type I errors when rejecting null hypotheses. In this context, the present article considers the utility of two (...) types of Type I error probability: the Neyman–Pearson long run Type I error rate and the Fisherian sample-specific Type I error probability. It is argued that the Neyman–Pearson Type I error rate is inapplicable in social science because it refers to a long run of exact replications, and social science deals with irreversible units that make exact replications impossible. Instead, the Fisherian sample-specific Type I error probability is recommended as a more meaningful way to conceptualize false positive results in social science because it can be applied to each sample-specific decision about rejecting the same substantive null hypothesis in a series of direct replications. It is concluded that the replication crisis may be partly due to researchers’ unrealistic expectations about replicability based on their consideration of the Neyman–Pearson Type I error rate across a long run of exact replications. (shrink)

Blindsight is a kind of residual vision found in people with lesions to V1. Subjects with blindsight typically report no visual awareness, but they are nonetheless able to make above-chance guesses about the shape, location, color and movement of visual stimuli presented to them in their blind field. A different kind of blindsight, sometimes called type 2 blindsight, is a kind of residual vision found in patients with V1 lesions in the presence of some residual awareness. Type 2 blindsight differs (...) from ordinary visual experience in lacking the particularity, transparency and fine-grainedness often taken to be essential to visual experience, at least in veridical cases. I argue that the case of type 2 blindsight provides a counterexample to the view that these characteristics are essential to veridical visual experience and that this gives us reason to resist the view that visual experience is essentially a perceptual relation to external objects. In the second part of the paper I argue that the case of type 2 blindsight yields important insights into the effects of attentional modulation on perceptual content and that cases of attentional modulation of appearance are not at odds with the view that the phenomenology of visual experience flows from its content. (shrink)

In this article I examine several related views expressed by Robin Hendry concerning molecular structure, emergence and chemical bonding. There is a long-standing problem in the philosophy of chemistry arising from the fact that molecular structure cannot be strictly derived from quantum mechanics. Two or more compounds which share a molecular formula, but which differ with respect to their structures, have identical Hamiltonian operators within the quantum mechanical formalism. As a consequence, the properties of all such isomers (...) yield precisely the same calculated quantities such as their energies, dipole moments etc. The only means through which the difference between the isomers can be recovered is to build their structures into the quantum mechanical calculations, something that is carried out by the application of the Born-Oppenheimer approximation. Consequently, it has been argued by many authors that molecular structure is written in ‘by hand’ rather than derived. Robin Hendry is one such author, but he goes a great deal further by proposing that this situation implies the existence of emergence and downward causation. In the current article I argue that there are alternative explanations which render emergence and downward causation redundant. Such an alternative lies in the notion of quantum decoherence and the appeal to work in the foundations of physics, which posits that the various isomers exist as a superposition until their wavefunctions are collapsed either by observation or by interacting with their environment. Hendry also alludes to a debate among chemists as to whether chemical bonds are real or not, in the sense of directional connections between two or more nuclei in any given molecule. I reject this view and propose that the structural and energetic views of chemical bonding, that have been discussed by some philosophers of chemistry including Hendry, do not refer to any essential ontological differences. I agree that chemists view bonding in a more realistic fashion and may consider bonds to be in some senses real, while physicists may consider bonding in more abstract energetic terms. However, I do not believe that such differences in scientific practice and attitudes should be considered to offer a window as to the ontological status of bonding or whether bonding is real. Finally, I discuss the kinetic energy school of chemical bonding which would seem to challenge any notion of bonds as directional entities, since bonding is no longer regarded as being primarily due to the build-up of electron density between nuclei. (shrink)

Talk of different types of cells is commonplace in the biological sciences. We know a great deal, for example, about human muscle cells by studying the same type of cells in mice. Information about cell type is apparently largely projectible across species boundaries. But what defines cell type? Do cells come pre-packaged into different natural kinds? Philosophical attention to these questions has been extremely limited [see e.g., Wilson (Species: New Interdisciplinary Essays, pp 187–207, 1999; Genes and the Agents of Life, (...) 2005; Wilson et al. Philos Top 35(1/2):189–215, 2007)]. On the face of it, the problems we face in individuating cellular kinds resemble those biologists and philosophers of biology encountered in thinking about species: there are apparently many different (and interconnected) bases on which we might legitimately classify cells. We could, for example, focus on their developmental history (a sort of analogue to a species’ evolutionary history); or we might divide on the basis of certain structural features, functional role, location within larger systems, and so on. In this paper, I sketch an approach to cellular kinds inspired by Boyd’s Homeostatic Property Cluster Theory, applying some lessons from this application back to general questions about the nature of natural kinds. (shrink)

Types are fundamental for conceptual modeling and knowledge representation, being an essential construct in all major modeling languages in these fields. Despite that, from an ontological and cognitive point of view, there has been a lack of theoretical support for precisely defining a consensual view on types. As a consequence, there has been a lack of precise methodological support for users when choosing the best way to model general terms representing types that appear in a domain, and for building sound (...) taxonomic structures involving them. For over a decade now, a community of researchers has contributed to the development of the Unified Foundational Ontology (UFO) - aimed at providing foundations for all major conceptual modeling constructs. At the core of this enterprise, there has been a theory of types specially designed to address these issues. This theory is ontologically well- founded, psychologically informed, and formally characterized. These results have led to the development of a Conceptual Modelling language dubbed OntoUML, reflecting the ontological micro-theories comprising UFO. Over the years, UFO and OntoUML have been successfully employed on conceptual model design in a variety of domains including academic, industrial, and governmental settings. These experiences exposed improvement opportunities for both the OntoUML language and its underlying theory, UFO. In this paper, we revise the theory of types in UFO in response to empirical evidence. The new version of this theory shows that many of OntoUML’s meta-types (e.g. kind, role, phase, mixin) should be considered not as restricted to substantial types but instead should be applied to model endurant types in general, including relator types, quality types, and mode types. We also contribute with a formal characterization of this fragment of the theory, which is then used to advance a new metamodel for OntoUML (termed OntoUML 2). To demonstrate that the benefits of this approach are extended beyond OntoUML, the proposed formal theory is then employed to support the definition of UFO-based lightweight Semantic Web ontologies with ontological constraint checking in OWL. Additionally, we report on empirical evidence from the literature, mainly from cognitive psychology but also from linguistics, supporting some of the key claims made by this theory. Finally, we propose a computational support for this updated metamodel. (shrink)

// tl;dr A Proposition is a Way of Thinking // -/- This chapter is about type-theoretic approaches to propositional content. Type-theoretic approaches to propositional content originate with Hintikka, Stalnaker, and Lewis, and involve treating attitude environments (e.g. "Nate thinks") as universal quantifiers over domains of "doxastic possibilities" -- ways things could be, given what the subject thinks. -/- This chapter introduces and motivates a line of a type-theoretic theorizing about content that is an outgrowth of the recent literature on epistemic (...) modality, according to which contentful thought is broadly "informational" in its nature and import. The general idea here is that an object of thought is not a way *the world* could be, but rather a way *one's perspective* could be (with respect to a relevant representational question). I will spend the middle part of this chapter motivating and developing a version of this strategy that is, I’ll argue, well-suited to explaining clear phenomena concerning the attribution of perspectival attitudes -- in particular, attitudes towards loosely information-sensitive propositions -- with which extant approaches struggle. My overarching goal here will be to motivate a distinctive version of the "informational" approach -- the "Flexible Types" approach, which is based on the theory proposed in Charlow (2020). According to the Flexible Types approach, propositional attitude verbs are quantifiers over sets of possibilities, but a possibility is a type-flexible notion -- sometimes a possible world, sometimes a perspective, sometimes a set of possible worlds, sometimes a set of perspectives. -/- After introducing the Flexible Types approach, this chapter circles back to more traditional concerns for the analysis of propositions as types of possibilities -- Frege's Puzzle and the problem of Logical Omniscience. Here too the Flexible Types approach bears fruit. Although there are certainly significant differences -- I note some in the concluding section -- the gist of this theory is Hinitkkan or Lewisian in spirit (if not quite in letter). We can make progress on addressing the challenges for the analysis of propositional content in terms of types of possibilities, through empirically driven refinement of our notion of what kind of thing a "doxastic possibility" is. (shrink)

The orthodox view of proper names, Millianism, provides a very simple and elegant explanation of the semantic contribution of referential uses of names–names that occur as bare singulars and as the argument of a predicate. However, one problem for Millianism is that it cannot explain the semantic contribution of predicative uses of names. In recent years, an alternative view, so-called the-predicativism, has become increasingly popular. According to the-predicativists, names are uniformly count nouns. This straightforwardly explains why names can be used (...) predicatively, but is prima facie less congenial to an analysis of referential uses. To address this issue, the-predicativists argue that referential names are in fact complex determiner phrases consisting of a covert definite determiner and a count noun—and so, a referential name is a definite description. In this paper, I will argue that despite the appearance of increased theoretical complexity, the view that names are ambiguous between predicative and referential types is in fact superior to the unitary the-predicativist view. However, I will also argue that to see why this ambiguity view is better, we need to give up the standard Millian analysis. Consequently, I will first propose an alternative analysis of referential names that retains the virtues of Millianism, but provides an important explanatory connection to the predicative uses. Once this analysis of names is adopted, the explanation for why names are systematically ambiguous between referential and predicative types is both simple and elegant. Second, I will argue that the-predicativism has the appearance of being simpler than an ambiguity view, but is in fact unable to account for certain key properties of referential names without making ad hoc stipulations. (shrink)

I argue that imperatives express contents that are both cognitively and semantically related to, but nevertheless distinct from, modal propositions. Imperatives, on this analysis, semantically encode features of planning that are modally specified. Uttering an imperative amounts to tokening this feature in discourse, and thereby proffering it for adoption by the audience. This analysis deals smoothly with the problems afflicting Portner's Dynamic Pragmatic account and Kaufmann's Modal account. It also suggests an appealing reorientation of clause-type theorizing, in which the cognitive (...) act of updating on a typed sentence plays a central role in theorizing about both its semantics and role in discourse. (shrink)

In a series of papers Ladyman and Presnell raise an interesting challenge of providing a pre-mathematical justification for homotopy type theory. In response, they propose what they claim to be an informal semantics for homotopy type theory where types and terms are regarded as mathematical concepts. The aim of this paper is to raise some issues which need to be resolved for the successful development of their types-as-concepts interpretation.

Manfred Eigen employs the terms language and communication to explain key recombination processes of DNA as well as to explain the self-organization of human language and communication: Life processes as well as language and communication processes are governed by the logic of a molecular syntax, which is the exact depiction of a principally formalizable reality. The author of the present contribution demonstrates that this view of Manfred Eigen’s cannot be sufficiently substantiated and that it must be supplemented by an (...) approach based on linguistic pragmatics. (shrink)

Realism about types is the view that types are abstract and repeatable objects. Although type realists seem to agree that types, unlike properties, are objects in their own right, they argue that there is a metaphysically intimate tie between the existence conditions of types and properties. In particular, most type realists believe that types are, in a certain sense, determined by the properties that underlie them. I argue that this is a mistake, especially for those type realists who believe that (...) social and cultural types such as works of music and fiction or words are artifacts. I offer an alternative version of type realism where social and cultural types are dependent objects that should be understood in analogy with concrete artifacts. (shrink)

In this work, polystyrene/waste tires composites were prepared using the melt-mixing method.. The effect of the preparation conditions of the PS/waste tires composite is investigated in this work by using Gel permeation chromatography (GPC) technique. Stability at elevated temperatures were found to increase with the addition of waste tires to PS as confirmed by the results. GPC results indicate that the preparation conditions of the PS/waste tires composite has no effect on the Ps chains as indicated by GPC technique. The (...) signals of the GPC for unfilled and filled PS are similar. That evidences no thermo-mechanical chain degradation is taken place during the addition of the waste tires under the conditions of the melt-mixing process . (shrink)

It would be unwise to dismiss the possibility of human brain organoids developing sentience. However, scepticism about this idea is appropriate when considering current organoids. It is a point of consensus that a brainstem-dead human is not sentient, and current organoids lack a functioning brainstem. There are nonetheless troubling early warning signs, suggesting organoid research may create forms of sentience in the near future. To err on the side of caution, researchers with very different views about the neural basis of (...) sentience should unite behind the “brainstem rule”: if a neural organoid develops or innervates a functioning brainstem that registers and prioritizes its needs, regulates arousal, and leads to sleep-wake cycles, then it is a sentience candidate. If organoid research leads to the creation of sentience candidates, a moratorium or indefinite ban on the creation of the relevant type of organoid may be appropriate. A different way forward, more consistent with existing approaches to animal research, would be to require ethical review and harm-benefit analysis for all research on sentience candidates. (shrink)