Bivalent chromatin with active H3K4me3 and repressive H3K27me3 was initially identified in embryonic stem cells (ESCs) to poise expression of developmental genes upon lineage commitment. Since then, many more different bivalent modifications have been demonstrated in both ESCs and fully differentiated cells. Bivalency not only spatiotemporally controls gene transcription but also acts to fine‐tune the level of transcription during development. Although increasing number of studies demonstrated the functional significance of bivalent chromatin, the molecular connection of bivalent chromatin and transcriptional regulation (...) remains largely elusive. Recently, we showed Spindlin1/C11orf84 complex prefers to recognize the non‐canonical histone H3K4me3K9me3 bivalent mark, which is required for timely ribosomal RNA transcription. Here, we hypothesize the recognition of K4me3 and K9me3 at the same histone tail by Spindlin1/C11orf84 complex may serve as a general mechanism of conversion from a repressed to an active chromatin structure for transcriptional activation. (shrink)

It is possible to control to a large extent, via semiproper forcing, the parameters measuring the guessing density of the members of any given antichain of stationary subsets of ω1 . Here, given a pair of ordinals, we will say that a stationary set Sω1 has guessing density if β0=γ and , where γ is, for every stationary S*ω1, the infimum of the set of ordinals τ≤ω1+1 for which there is a function with ot)<τ for all νS* and with {νS*:gF} (...) stationary for every α<ω2 and every canonical function g for α. This work involves an analysis of iterations of models of set theory relative to sequences of measures on possibly distinct measurable cardinals. As an application of these techniques I show how to force, from the existence of a supercompact cardinal, a model of in which there is a well-order of H definable, over H,, by a formula without parameters. (shrink)

Hedgehog (Hh) signaling is a widely studied signaling pathway because of its critical roles during development and in cell homeostasis. Vertebrate canonical and non‐canonical Hh signaling are typically assumed to be distinct and occur in different cellular compartments. While research has primarily focused on the canonical form of Hh signaling and its dependency on primary cilia – microtubule‐based signaling hubs – an extensive list of crucial functions mediated by non‐canonical Hh signaling has emerged. Moreover, amounting (...) evidence indicates that canonical and non‐canonical modes of Hh signaling are interlinked, and that they can overlap spatially, and in many cases interact functionally. Here, we discuss some of the many cellular effects of non‐canonical signaling and discuss new evidence indicating inter‐relationships with canonical signaling. We discuss how Smoothened (Smo), a key component of the Hh pathway, might coordinate such diverse downstream effects. Collectively, pursuit of questions such as those proposed here will aid in elucidating the full extent of Smo function in development and advance its use as a target for cancer therapeutics. (shrink)

Wnt glycoproteins are signaling molecules that control a wide range of developmental processes in organisms ranging from the simple metazoan Hydra to vertebrates. Wnt signaling also plays a key role in the development of the nematode C. elegans, and is involved in cell fate specification and determination of cell polarity and cell migration. Surprisingly, the first genetic studies of Wnt signaling in C. elegans revealed major differences with the established (canonical) Wnt signaling pathways of Drosophila and vertebrates. Thus, the (...) Wnt-dependent induction of endoderm in the early embryo and the specification of several asymmetric cell divisions during larval development are mediated by as yet novel Wnt signaling pathways that repress, rather than activate the TCF/LEF-1 transcription factor POP-1. Recently, however, it has been shown that, in addition to these divergent Wnt pathways, C. elegans also has a canonical Wnt pathway that converts POP-1 into an activator and controls the expression of several homeobox genes. Interestingly, these different Wnt pathways use distinct beta-catenins to control POP-1 function: the endoderm induction pathway requires the beta-catenin WRM-1 and parallel input from a mitogen-activated kinase (MAPK) pathway to downregulate POP-1, whereas the canonical Wnt pathway employs the beta-catenin BAR-1 to activate Wnt target gene expression. (shrink)

In metazoans, the extracellular matrix (ECM) provides a dynamic, heterogeneous microenvironment that has important supportive and instructive roles. Although the primary site of action of ECM proteins is extracellular, evidence is emerging for non‐canonical intracellular roles. Examples include osteopontin, thrombospondins, IGF‐binding protein 3 and biglycan, and relate to roles in transcription, cell‐stress responses, autophagy and cancer. These findings pose conceptual problems on how proteins signalled for secretion can be routed to the cytosol or nucleus, or can function in environments (...) with diverse redox, pH and ionic conditions. We review evidence for intracellular locations and functions of ECM proteins, and current knowledge of the mechanisms by which they may enter intracellular compartments. We evaluate the experimental methods that are appropriate to obtain rigorous evidence for intracellular localisation and function. Better insight into this under‐researched topic is needed to decipher the complete spectrum of physiological and pathological roles of ECM proteins. -/- . (shrink)

Rho GTPases are critically important and are centrally positioned regulators of the actomyosin cytoskeleton. By influencing the organization and architecture of the cytoskeleton, Rho proteins play prominent roles in many cellular processes including adhesion, migration, intra‐cellular transportation, and proliferation. The most important method of Rho GTPase regulation is via the GTPase cycle; however, post‐translational modifications (PTMs) also play critical roles in Rho protein regulation. Relative to other PTMs such as lipidation or phosphorylation that have been extensively characterized, protein oxidation is (...) a regulatory PTM that has been poorly studied. Protein oxidation primarily occurs from the reaction of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), with amino acid side chain thiols on cysteine (Cys) and methionine (Met) residues. The versatile redox modifications of cysteine residues exemplify their integral role in cell signalling processes. Here we review prominent members of the Rho GTPase family and discuss how lipidation, phosphorylation, and oxidation on conserved cysteine residues affects their regulation and function. (shrink)

We construct an algebra of generalized functions endowed with a canonical embedding of the space of Schwartz distributions.We offer a solution to the problem of multiplication of Schwartz distributions similar to but different from Colombeau’s solution.We show that the set of scalars of our algebra is an algebraically closed field unlike its counterpart in Colombeau theory, which is a ring with zero divisors. We prove a Hahn–Banach extension principle which does not hold in Colombeau theory. We establish a (...) connection between our theory with non-standard analysis and thus answer, although indirectly, a question raised by Colombeau. This article provides a bridge between Colombeau theory of generalized functions and non-standard analysis. (shrink)

Human telomerase progressively emerged as a multifaceted ribonucleoprotein complex with additional functions beyond telomeric repeat synthesis. Both the hTERT catalytic subunit and the hTR long non‐coding RNA (lncRNA) subunit are engaged in highly regulated cellular pathways that, together, contribute to cell fitness and protection against apoptosis. We recently described a new role for hTR in regulating the abundance of replication protein A at telomeres, adding to the growing repertoire of hTR’s functions. Here, we focus on the non‐canonical (...) roles of hTR and discuss them in the context of the structural elements of the lncRNA. We propose that some functions of hTR may compete amongst each other through distinct interactions with its partners, proteins or mRNAs. We postulate that hTR’s non‐canonical functions may be highly relevant in the context of normal somatic cells that naturally silence hTERT gene, while keeping hTR expression. (shrink)

The procedures of canonical quantization of the gravitational field apparently lead to entities for which any interpretation in terms of spatio-temporal localization or spatio-temporal extension seems difficult. This fact is the main ground for the suggestion that can often be found in the physics literature on canonical quantum gravity according to which spacetime may not be fundamental in some sense. This paper aims to investigate this radical suggestion from an ontologically serious point of view in the cases of (...) two standard forms of canonical quantum gravity, quantum geometrodynamics and loop quantum gravity. We start by discussing the physical features of the quantum wave functional of quantum geometrodynamics and of the spin networks of loop quantum gravity that motivate the view according to which spacetime is not fundamental. We then point out that, by contrast, for any known ontologically serious understanding of quantum entanglement, the commitment to spacetime seems indispensable. Against this background, we then critically discuss the idea that spacetime may emerge from more fundamental entities. As a consequence, we finally suggest that the emergence of classical spacetime in canonical quantum gravity faces a dilemma: either spacetime ontologically emerges from more fundamental non-spatio-temporal entities or it already belongs to the fundamental quantum gravitational level and the emergence of the classical picture is merely a matter of levels of description. On the first horn of the dilemma, it is unclear how to make sense of concrete physical entities that are not in spacetime and of the notion of ontological emergence that is involved. The second horn runs into the difficulties raised by the physics of canonical quantum gravity. (shrink)

The purpose of this paper is to determine the meaning and function of mindfulness meditation using as the source of inquiry the Pāli Canon, the oldest complete collection of Buddhist texts to survive intact. Mindfulness is the chief factor in the practice of satipa hāna, the best known system of Buddhist meditation. In descriptions of satipa hāna two terms constantly recur: mindfulness (sati) and clear comprehension (sampajañña). An understanding of these terms based on the canonical texts is important not (...) only from a philological angle but because such understanding has major bearings on the actual practice of meditation. The word sati originally meant ‘memory,’ but the Buddha ascribed to this old term a new meaning determined by the aims of his teaching. This meaning, the author holds, might best be characterized as ‘lucid awareness.’ He questions the common explanation of mindfulness as ‘bare attention,’ pointing out problems that lurk behind both words in this expression. He also briefly discusses the role of clear comprehension (sampajañña) and shows that it serves as a bridge between the observational function of mindfulness and the development of insight. Finally, he takes up the question whether mindfulness can legitimately be extracted from its traditional context and employed for secular purposes. He maintains that such non-traditional applications of mindfulness are acceptable and even admirable on the ground that they help alleviate human suffering, but he also cautions against a reductionist understanding of mindfulness and urges that investigators respect the religious tradition in which it is rooted. (shrink)

Although it has been argued that mechanistic explanation is compatible with abstraction, there are still doubts about whether mechanism can account for the explanatory power of significant abstract models in computational neuroscience. Chirimuuta has recently claimed that models describing canonical neural computations must be evaluated using a non-mechanistic framework. I defend two claims regarding these models. First, I argue that their prevailing neurocognitive interpretation is mechanistic. Additionally, a criterion recently proposed by Levy and Bechtel to legitimize mechanistic abstract models, (...) and also a criterion proposed by Chirimuuta herself aimed to distinguish between causal and non-causal explanation, can be employed to show why these models are explanatory only under this interpretation. Second, I argue that mechanism is able to account for the special epistemic achievement implied by CNC models. Canonical neural components contribute to an integrated understanding of different cognitive functions. They make it possible for us to explain these functions by describing different mechanisms constituted by common basic components arranged in different ways. (shrink)

Conwy Lloyd Morgan (1852–1936) is widely regarded as the father of modern comparative psychology. Yet, Morgan initially had significant doubts about whether a genuine science of comparative psychology was even possible, only later becoming more optimistic about our ability to make reliable inferences about the mental capacities of non-human animals. There has been a fair amount of disagreement amongst scholars of Morgan’s work about the nature, timing, and causes of this shift in Morgan’s thinking. We argue that Morgan underwent two (...) quite different shifts of attitude towards the proper practice of comparative psychology. The first was a qualified acceptance of the Romanesian approach to comparative psychology that he had initially criticized. The second was a shift away from Romanes’ reliance on systematizing anecdotal evidence of animal intelligence towards an experimental approach, focused on studying the development of behaviour. We emphasize the role of Morgan’s evolving epistemological views in bringing about the first shift – in particular, his philosophy of science. We emphasize the role of an intriguing but overlooked figure in the history of comparative psychology in explaining the second shift, T. Mann Jones, whose correspondence with Morgan provided an important catalyst for Morgan’s experimental turn, particularly the special focus on development. We also shed light on the intended function of Morgan’s Canon, the methodological principle for which Morgan is now mostly known. The Canon can only be properly understood by seeing it in the context of Morgan’s own unique experimental vision for comparative psychology. (shrink)

A religion with Buddhism's particular moral philosophies of non-violence and asceticism and with its *functional* polytheism in practice should not generate genocidal nationalist violence. Yet, there are resources within the Buddhist canon that people can draw from to justify violence in defense of the religion and of a Buddhist-based polity. When those resources are exploited, for example in the context of particular Theravāda Buddhist practices and the history of Buddhism and Buddhist identity in Burma from ancient times through its colonial (...) and contemporary periods, it perpetuates an ongoing tragedy that is less about religion than about ethno-nationalism. (shrink)

Over the last decade, our appreciation of the importance of the nucleolus for cellular function has progressed from the ordinary to the extraordinary. We no longer think of the nucleolus as simply the site of ribosome production, or a dynamic subnuclear body noted by pathologists for its changes in size and shape with malignancy. Instead, the nucleolus has emerged as a key controller of many cellular processes that are fundamental to normal cell homeostasis and the target for dysregulation in many (...) human diseases; in some cases, independent of its functions in ribosome biogenesis. These extra‐nucleolar or new functions, which we term “non‐canonical” to distinguish them from the more traditional role of the nucleolus in ribosome synthesis, are the focus of this review. In particular, we explore how these non‐canonical functions may provide novel insights into human disease and in some cases new targets for therapeutic development. (shrink)

The noncoding RNA 7SK is a critical regulator of transcription by adjusting the activity of the kinase complex P‐TEFb. Release of P‐TEFb from 7SK stimulates transcription at many genes by promoting productive elongation. Conversely, P‐TEFb sequestration by 7SK inhibits transcription. Recent studies have shown that 7SK functions are particularly important for neuron development and maintenance and it can thus be hypothesized that 7SK is at the center of many signaling pathways contributing to neuron function. 7SK activates neuronal gene expression (...) programs that are key for terminal differentiation of neurons. Proteomics studies revealed a complex protein interactome of 7SK that includes several RNA‐binding proteins. Some of these novel 7SK subcomplexes exert non‐canonical cytosolic functions in neurons by regulating axonal mRNA transport and fine‐tuning spliceosome production in response to transcription alterations. Thus, a picture emerges according to which 7SK acts as a multi‐functional RNA scaffold that is integral for neuron homeostasis. (shrink)

In this paper I offer an interpretation of Kant’s theory of perceptual error based on his remarks in the Anthropology. Both hallucination and illusion, I argue, are for Kant species of experience and therefore require the standard co-operation of sensibility and understanding. I develop my account in a conceptualist framework according to which the two canonical classes of non-veridical experience involve error in the basic sense that how they represent the world as being is not how the world is. (...) In hallucination this is due to the misapplication of categories and in illusion to the misapplication of empirical concepts. Yet there is also room in this framework for a distinction in terms of cognitive functionality between the level of experience, which is merely judgementally structured, and that of judgement proper, which involves the free action of a conscious agent. This distinction enables Kant to allow for the otherwise problematic phenomenon of self-aware non-veridicality. (shrink)

Hamiltonian constraints feature in the canonical formulation of general relativity. Unlike typical constraints they cannot be associated with a reduction procedure leading to a non-trivial reduced phase space and this means the physical interpretation of their quantum analogues is ambiguous. In particular, can we assume that “quantisation commutes with reduction” and treat the promotion of these constraints to operators annihilating the wave function, according to a Dirac type procedure, as leading to a Hilbert space equivalent to that reached by (...) quantisation of the problematic reduced space? If not, how should we interpret Hamiltonian constraints quantum mechanically? And on what basis do we assert that quantisation and reduction commute anyway? These questions will be refined and explored in the context of modern approaches to the quantisation of canonical general relativity. (shrink)

Recent experimental evidence suggests that most of the genome is transcribed into non‐coding RNAs. The initial transcripts undergo further processing generating shorter, metabolically stable RNAs with diverse functions. Small nucleolar RNAs (snoRNAs) are non‐coding RNAs that modify rRNAs, tRNAs, and snRNAs that were considered stable. We review evidence that snoRNAs undergo further processing. High‐throughput sequencing and RNase protection experiments showed widespread expression of snoRNA fragments, known as snoRNA‐derived RNAs (sdRNAs). Some sdRNAs resemble miRNAs, these can associate with argonaute proteins (...) and influence translation. Other sdRNAs are longer, form complexes with hnRNPs and influence gene expression. C/D box snoRNA fragmentation patterns are conserved across multiple cell types, suggesting a processing event, rather than degradation. The loss of expression from genetic loci that generate canonical snoRNAs and processed snoRNAs results in diseases, such as Prader‐Willi Syndrome, indicating possible physiological roles for processed snoRNAs. We propose that processed snoRNAs acquire new roles in gene expression and represent a new class of regulatory RNAs distinct from canonical snoRNAs.Also watch the Video Abstract. (shrink)

This paper generalises an argument for probabilism due to Lindley [9]. I extend the argument to a number of non-classical logical settings whose truth-values, seen here as ideal aims for belief, are in the set $\{0,1\}$, and where logical consequence $\models $ is given the “no-drop” characterization. First I will show that, in each of these settings, an agent’s credence can only avoid accuracy-domination if its canonical transform is a (possibly non-classical) probability function. In other words, if an agent (...) values accuracy as the fundamental epistemic virtue, it is a necessary requirement for rationality that her credence have some probabilistic structure. Then I show that for a certain class of reasonable measures of inaccuracy, having such a probabilistic structure is sufficient to avoid accuracy-domination in these non-classical settings. (shrink)

We show that the electromagnetic radiation field, conventionally introduced as a perturbation in quantum mechanics, is actually at the basis of the operator formalism. We first analyze the linear resonant response of the (continuous) variables x(t), p(t) of a harmonic oscillator to the full radiation field, i.e. the zero-point field plus an applied field playing the role of the driving force, and then extend the analysis to the response of a charged particle bound by a non-linear force, typically an atomic (...) electron. This leads to the establishment of a one-to-one correspondence between the response functions and the respective quantum operators, and to the identification of the quantum commutator with the Poisson bracket of the response functions with respect to the normalized variables of the driving field. To complete the quantum description, a similar procedure is used to obtain the field operators as the response functions to the same normalized variables. The results allow us to draw important conclusions about the physical content of the quantum formalism, in particular about the meaning of the quantum expectation values and the coarse-grained nature of the quantum-mechanical description. (shrink)

The last 30 years has seen the emergence of a self-styled ‘evolutionary’ paradigm within psychology (henceforth, EP). EP is often presented and critiqued as a distinctive, contentious paradigm, to be contrasted with other accounts of human psychology. However, little attention has been paid to the sense in which those other accounts are not also evolutionary. We outline the core commitments of canonical EP. These are, from least distinctive to most: mechanism, interactionism, functionalism, adaptationism, and functional specialization. We argue that (...) the minimal requirement for an approach to psychology to qualify as evolutionary in an important sense is functionalism. This is because the notion of functional design in organismal structures presupposes a history of evolution by natural selection. On this criterion, we argue, most, perhaps all of psychology qualifies as evolutionary, either implicitly or explicitly. We review several approaches that are typically contrasted with EP, showing that these are all evolutionary too by our criteria. We suggest that the EP/non-EP dichotomy be retired. However, though all psychology is evolutionary, psychologists do not always need to foreground evolution in their research, just as is true for biologists. At the same time, more space for evolution does not mean any less space for environment, context, culture, meaning or agency. (shrink)

Gemins 2–8 and Unr‐interacting protein (UNRIP) are intimate partners of the survival motor neuron (SMN) protein, which is the determining factor for the neuromuscular disorder spinal muscular atrophy (SMA). The most documented role of SMN, Gemins and UNRIP occurs within the large macromolecular SMN complex and involves the cytoplasmic assembly of spliceosomal uridine‐rich small nuclear ribonucleoproteins (UsnRNPs), a housekeeping process critical in all cells. Several reports detailing alternative functions for SMN in either motor neurons or skeletal muscles may, however, (...) hold the answer to the extreme neuromuscular tissue specificity observed in SMA. Recent discoveries indicate that collaboration between SMN and Gemins also extends to these non‐canonical functions, hence raising the possibility that mutations in Gemin genes may be the cause of unlinked neuromuscular hereditary syndromes. This review evaluates the functions of Gemins and UNRIP inside the SMN complex and discusses whether these less notorious SMN complex members are capable of acting independently of SMN. (shrink)

The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway is central for the initiation of anti‐tumoural immune responses. Enormous effort has been made to optimise the design and administration of STING agonists to stimulate tumour immunogenicity. However, in certain contexts the cGAS‐STING axis fuels tumourigenesis. Here, we review recent findings on the regulation of cGAS expression and activity. We particularly focus our attention on the DNA‐dependent protein kinase (DNA‐PK) complex, that recently emerged as an activator of inflammatory responses in tumour (...) cells. We propose that stratification analyses on cGAS and DNA‐PK expression/activation status should be carried out to predict treatment efficacy. We herein also provide insights into non‐canonical functions borne by cGAS and cGAMP, highlighting how they may influence tumourigenesis. All these parameters should be taken into consideration concertedly to choose strategies aiming to effectively boost tumour immunogenicity. (shrink)

We study complex phenomena arising from a simple optimal choice consumer model, starting from the classical framework in Benhabib and Day :459–471, 1981). We introduce elements of increasing complexity and we investigate their effects on the resulting social behaviors. The dynamics introduce the dependence of current preferences on past consumers actions. A non-monotone updating preference function allows us to obtain a threshold effect, according to which the agents adopt a bandwagon/snob behavior if the preferences are below/above a certain saturation level. (...) We consider homogeneous and heterogeneous agents and we introduce local/global interaction when they are spatially distributed. We show through simulations several phenomena which are absent in the classical model and which reproduce significant social behaviors, such as path dependence, coexistence of different periodic and chaotic attractors, emergence of spatial patterns. (shrink)

Classical electron theory with classical electromagnetic zero-point radiation (stochastic electrodynamics) is the classical theory which most closely approximates quantum electrodynamics. Indeed, in inertial frames, there is a general connection between classical field theories with classical zero-point radiation and quantum field theories. However, this connection does not extend to noninertial frames where the time parameter is not a geodesic coordinate. Quantum field theory applies the canonical quantization procedure (depending on the local time coordinate) to a mirror-walled box, and, in general, (...) each non-inertial coordinate frame has its own vacuum state. In particular, there is a distinction between the “Minkowski vacuum” for a box at rest in an inertial frame and a “Rindler vacuum” for an accelerating box which has fixed spatial coordinates in an (accelerating) Rindler frame. In complete contrast, the spectrum of random classical zero-point radiation is based upon symmetry principles of relativistic spacetime; in empty space, the correlation functions depend upon only the geodesic separations (and their coordinate derivatives) between the spacetime points. The behavior of classical zero-point radiation in a noninertial frame is found by tensor transformations and still depends only upon the geodesic separations, now expressed in the non-inertial coordinates. It makes no difference whether a box of classical zero-point radiation is gradually or suddenly set into uniform acceleration; the radiation in the interior retains the same correlation function except for small end-point (Casimir) corrections. Thus in classical theory where zero-point radiation is defined in terms of geodesic separations, there is nothing physically comparable to the quantum distinction between the Minkowski and Rindler vacuum states. It is also noted that relativistic classical systems with internal potential energy must be spatially extended and can not be point systems. The classical analysis gives no grounds for the “heating effects of acceleration through the vacuum” which appear in the literature of quantum field theory. Thus this distinction provides (in principle) an experimental test to distinguish the two theories. (shrink)

Programmed cell death (PCD) or apoptosis is a broadly conserved phenomenon in metazoans, whereby activation of canonical signal pathways induces an ordered dismantling and death of a cell. Paradoxically, the constituent proteins and pathways of PCD (most notably the metacaspase/caspase protease mediated signal pathways) have been demonstrated to retain non‐death functions across all phyla including yeast, nematodes, drosophila, and mammals. The ancient conservation of both death and non‐death functions of PCD proteins raises an interesting evolutionary conundrum: was (...) the primordial intent of these factors to induce cell death or to regulate other cellular adaptations? Here, we propose the hypothesis that apoptotic behavior of PCD proteins evolved or were co‐opted from core non‐death functions. (shrink)

Fanconi anemia (FA) is generally classified as a DNA repair disorder, conferring a genetic predisposition to cancer and prominent bone marrow failure (BMF) in early childhood. Corroborative human and murine studies point to a fetal origin of hematopoietic stem cell (HSC) attrition under replicative stress. Along with intriguing recent insights into non‐canonical roles and domain‐specific functions of FA proteins, these studies have raised the possibility of a DNA repair‐independent BMF etiology. However, deeper mechanistic insight is critical as current (...) curative options of allogeneic stem cell transplantation and emerging gene therapy have limited eligibility, carry significant side effects, and involve complex procedures restricted to resource‐rich environments. To develop rational and broadly accessible therapies for FA patients, the field will need more faithful disease models that overcome the scarcity of patient samples, leverage technological advances, and adopt investigational clinical trial designs tailored for rare diseases. (shrink)

• We define a notion of order of indiscernibility type of a structure by analogy with Mitchell order on measures; we use this to define a hierarchy of strong axioms of infinity defined through normal filters, the α-weakly Erdős hierarchy. The filters in this hierarchy can be seen to be generated by sets of ordinals where these indiscernibility orders on structures dominate the canonical functions.• The limit axiom of this is that of greatly Erdős and we use it (...) to calibrate some strengthenings of the Chang property, one of which, CC+, is equiconsistent with a Ramsey cardinal, and implies that where K is the core model built with non-overlapping extenders — if it is rigid, and others which are a little weaker. As one corollary we have:TheoremIf then there is an inner model with a strong cardinal. • We define an α-Jónsson hierarchy to parallel the α-Ramsey hierarchy, and show that κ being α-Jónsson implies that it is α-Ramsey in the core model. (shrink)

In the first chapter, we discuss Dummett’s idea that the notion of truth arises from the one of the correctness of an assertion. We argue that, in a first-order language, the need of defining truth in terms of the notion of satisfaction, which is yielded by the presence of quantifiers, is structurally analogous to the need of a notion of truth as distinct from the one of correctness of an assertion. In the light of the analogy between predicates in Frege (...) and open formulas in Tarksi, we concentrate on the semantic status of predicates. We register a dual attitude of Dummett towards Frege’s ascription of reference to predicates. On the one it is needed to endow quantifiers with their appropriate meaning. On the other hand, the introduction of concepts, as semantic correlate of predicates, smuggles a realist flavor in the overall semantic picture. In concluding the excursus (and with it the chapter), we stress Dummett’s will of developing a semantic picture free from this realist trait. In the second chapter, we present the idea of a proof-theoretic semantics. As for Frege true sentences denotes the truth-value True, so here closed' (i.e. categorical) valid argumentations denotes proofs. If a language contains implication-like operators, in order to characterize the condition of validity of a closed argumentation one has to introduce a notion of validity applying to ‘open’ (i.e. hypothetical) argumentations. We argue that this problem is analogous to the one posed by quantifiers in Frege-Tarksi’s style semantics. That is, implication forces one to introduce notion of validity for argumentations, which is more substantial than the correctness of the assertion of their conclusions. As we saw, the corresponding claim in the truth-based approach—that quantifiers require one to introduce a notion of truth, which is more substantial than the one of an assertion being correct—was the source of realism. Hence, Dummett proposes to reduce the semantic contribution of open argumentations to the one of their ‘closed instances’. In the truth-based perspective, this would correspond to the denial of the need of introducing concepts as the semantic correlates of predicates. We argue that Dummett’s fear, that an irreducible notion of function (represented by the need of ascribing validity to open argumentations) would lead to realism, turns out to be ill-founded. In the third chapter, we discuss the role played by the notion of truth in the anti-realist account. The notion of truth is what the anti-realist needs to cope with the so-called paradox of deduction. The analysis of the paradox yields to distinguishing between the truth of a sentence and the truth of a sentence being recognized. In terms of these conceptual couple, we reconsider the relationship between truth and assertion in an anti-realist perspective. Grounds are provided for a thesis (which was already advanced in chapter two), according to which the notion of the assertion of a sentence being correct is primarily connected only with the canonical means of establishing a sentence. The possibility of establishing a sentence by indirect means is conceptually dependent on the practice of establishing logical relationship of dependence among sentences. That is, the notion of a closed valid non-canonical argumentation is of any theoretical relevance only in presence of a notion of validity applying to open argumentations. In the fourth chapter, we discuss the possibility of characterizing in the proof-theoretic-semantics a notion of refutation. We develop an original characterization of refutations starting from an informal inductive specification of the condition of refutations of logically complex sentences. A sub-structural logic, called dual-intuitionistic logic, stands to this notion in the same relationship in which intuitionistic logic stands to the notion of proof so far consdered. All notions developed in chapter 2 have their corresponding (dual) ones in the framework developed. In particular, the distinctions canonical/non-canonical and closed/open argumentations. In the refutation based perspective, elimination rules have priority over introductions and the (only) assumption over the (many) conclusions. In the conclusions, we indicate the ingredients that an anti-realist approach to meaning should incorporate, in order to avoid the difficulties we registered. The core of an alternative view is a different conception of the relationship between categorical and hypothetical notions, in which the validity of open argumentations is not reduced to that of their instances, but rather it is directly defined. As a limit case, one would get a notion of validity applying to closed argumentations. (shrink)

The canonical function game is a game of length ω1 introduced by W. Hugh Woodin which falls inside a class of games known as Neeman games. Using large cardinals, we show that it is possible to force that the game is not determined. We also discuss the relationship between this result and Σ22 absoluteness, cardinality spectra and Π2 maximality for H(ω2) relative to the Continuum Hypothesis.

We review the relation between spacetime geometries with trace-torsion fields, the so-called Riemann–Cartan–Weyl (RCW) geometries, and their associated Brownian motions. In this setting, the drift vector field is the metric conjugate of the trace-torsion one-form, and the laplacian defined by the RCW connection is the differential generator of the Brownian motions. We extend this to the state-space of non-relativistic quantum mechanics and discuss the relation between a non-canonical quantum RCW geometry in state-space associated with the gradient of the quantum-mechanical (...) expectation value of a self-adjoint operator given by the generalized laplacian operator defined by a RCW geometry. We discuss the reduction of the wave function in terms of a RCW quantum geometry in state-space. We characterize the Schroedinger equation in terms of the RCW geometries and Brownian motions. Thus, in this work, the Schroedinger field is a torsion generating field, both for the linear and non-linear cases. We discuss the problem of the many times variables and the relation with dissipative processes, and the role of time as an active field, following Kozyrev and a recent experiment in non-relativistic quantum systems. We associate the Hodge dual of the drift vector field with a possible angular-momentum source for the phenomenae observed by Kozyrev. (shrink)

We define a class of formal systems inspired by Prawitz’s theory of grounds. The latter is a semantics that aims at accounting for epistemic grounding, namely, at explaining why and how deductively valid inferences have the power to epistemically compel to accept the conclusion. Validity is defined in terms of typed objects, called grounds, that reify evidence for given judgments. An inference is valid when a function exists from grounds for the premises to grounds for the conclusion. Grounds are described (...) by formal terms, either directly when the terms are in canonical form, or indirectly when they are in non-canonical form. Non-canonical terms must reduce to canonical form, and two terms may be said to be equal when they converge towards equivalent grounds. In our systems these properties can be proved through rules distinguished according to whether they concern types or logic. Type rules involve type introduction and elimination, equality for application of operational symbols, and re-writing equations for non-canonical terms. The logic amounts to a sort of intuitionistic system in a Gentzen format. To conclude, we show that each system of our class enjoys a normalization property. (shrink)

This paper is an initial effort preparatory for a more thorough “theology of joys.” I distinguish joys from other kinds of pleasure and argue that joy can be seen as the form of all the so-called positive emotions. So joy is properly treated in the plural: joys come in a variety of kinds. I distinguish canonical from non-canonical joys. The worthiness of joys is primarily a function of their objects—what the joys are about. I look at a few (...) examples of joys that appear in the New Testament and sketch the relation of joys to happiness. (shrink)

Kōūhala’s Līlāvaī, a romance in Prakrit verse from around 800 CE, has two types of constructions that present “syntactical difficulties” : the use of mhi in the meaning of maē, and the use of amhēhi and tumhēhi in the meanings of amhē and tumhē. This article reviews the phenomena and puts them into the context of expressions of agency in related Indic languages, arguing that Prakrit’s split ergativity is implicated in both cases. A further conclusion is that the particle hi (...) is all but absent from Kōūhala’s Prakrit. (shrink)

This paper is about the question: what is it for a mental state to mean (or present) something as an intentional object? This issue is addressed from a broad perspective, against the background of Brentano’s philosophical programme in Psychology from an empirical standpoint, and the controversy between the proponents of a non-canonical interpretation of Brentano’s theory of intentionality, and the so-called orthodox interpretation advocated namely by R. Chisholm. My investigation is divided into six parts. In the first section, I (...) explain the meaning and function of the notion of phenomenon in light of Brentano’s philosophical programme, and I briefly elucidate the notion of physical phenomenon which, in Brentano’s Psychology, constitutes the primary object of consciousness. In the next two sections, I look at two aspects of Brentano’s criticism of the identity thesis that he attributes to British empiricism, namely the psychological aspect, which concerns the identification of the two classes of phenomena, and the metaphysical aspect relating to the relationship between physical phenomena and the reality of an extramental world. Once this double distinction will be established, I will turn to the relation of intentional objects to presentations and put forward the hypothesis that intentional objects are conceptually dependent upon presentations and that this dependence rests, in turn, upon the content of the mental phenomena. The next step concerns Brentano’s theory of primary and secondary objects, and one of the main non-orthodox arguments against the canonical interpretation, namely that the latter conflates primary and secondary objects. In this context, I examine a second hypothesis: that the secondary object, or intentional correlate of an act, is an intentional content, which is distinct both from the intentional object and from the reality to which it relates, and I maintain that the intentional content has the function of mediating the mental acts’ relation to their objects. Finally, I shall examine some objections against the hypothesis of intentional content in Brentano’s Psychology, and I will conclude with a brief commentary on the bearing of this investigation with regard to the interpretation of the genesis of Brentano’s theory of intentionality, before and after the reistic turn of his philosophy. (shrink)

Consider truth predicates. Minimalist analyses of truth predicates may involve commitment to some of the following claims: (i) truth “predicates” are not genuine predicates -- either because the truth “predicate” disappears under paraphrase or translation into deep structure, or because the truth “predicate” is shown to have a non-predicative function by performative or expressivist analysis, or because truth “predicates” must be traded in for predicates of the form “true-in-L”; (ii) truth predicates express ineligible, non-natural, gerrymandered properties; (iii) truth predicates express (...) metaphysically lightweight properties; (iv) truth predicates have thin conceptual roles; (v) truth predicates express properties with no hidden essence; (vi) truth predicates express properties which have no causal or explanatory role in canonical formulations of fundamental theories. -/- This paper is unpublished, and likely to remain so. (shrink)

Originating in the United States, a Gay/Straight Alliance (GSA) is an in-school student club whose focus is on making the school a safe space for lesbian, gay, bisexual, transgender and queer students and their straight allies by raising awareness about, and hopefully reducing, school-based homophobia. The ongoing struggle for GSAs in Canadian Catholic schools is one example of how clashes continue to be played out between Catholic canonical law and Canadian common law regarding sexual minorities. This paper draws upon (...) Foucault’s Discipline and Punish: The Birth of the Prison, and The History of Sexuality Vol. 1: An Introduction to analyze one particularly influential curricular and policy document entitled Pastoral Guidelines to Assist Students of Same-Sex Orientation from the Ontario Conference of Catholic Bishops. This paper posits that Catholic doctrine about non-heterosexuality functions as a Foucaultian Panopticon enabling Catholic education leaders to observe and correct the behaviour of non-heterosexual teachers and students that they deem runs counter to the values of the Vatican. This paper argues that successful resistance to the powerful disciplining regime of the Catholic school is possible. (shrink)

Prior research has shown that various types of conventional multiword chunks are processed faster than matched novel strings, but it is unclear whether this processing advantage extends to variant multiword chunks that are less formulaic. To determine whether the processing advantage of multiword chunks accommodates variations in the canonical phrasal template, we examined the robustness of the processing advantage (i.e., predictability) of binomial phrases with non‐canonical conjunctions (e.g.,salt and also pepper; salt as well as pepper). Results from the (...) cloze study (Experiment 1) showed that there was a high tendency of producing the canonical conjunct (pepper), even in the binomials that contained non‐formulaic conjunctions. Consistent with these findings, results from two eye tracking studies (Experiments 2a and 2b) showed that canonical conjuncts were read faster than novel conjuncts that were matched on word length (e.g.,paprika), even in the binomials with variant conjunctions. This robust online processing advantage was replicated in a self‐paced reading study that compared all three conjunction types (Experiment 3). Taken together, these findings show that binomials with variant function words also receive facilitated processing relative to matched novel strings, even though both types of strings are neither conventional nor relatively frequent. Exploratory analyses revealed that this processing speed advantage was driven by the lexical–semantic association between the canonical conjuncts (salt–pepper), rather than lexical and phrasal frequency. Overall, these results highlight flexibility in the processing of multiword chunks that current models of multiword storage and processing must take into account. (shrink)

A function f from ω1 to the ordinals is called a canonical function for an ordinal α if f represents α in any generic ultrapower induced by forcing with math formula. We introduce here a method for coding sets of ordinals using canonical functions from ω1 to ω1. Combining this approach with arguments from, we show, assuming the Continuum Hypothesis, that for each cardinal κ there is a forcing construction preserving cardinalities and cofinalities forcing that every subset (...) of κ is an element of the inner model math formula. (shrink)

This article discusses the English construction variously known as Locative Inversion or Stylistic Inversion. It shows that the construction displays a unique ensemble of grammatical and usage properties that can be stated but not motivated through purely grammatical means. In search of an explanatory approach, an analysis is presented that draws on concepts of Artificial Intelligence, in particular plans viewed as complex mental attitudes. It is claimed that utterances of Locative Inversion are associated with a particular communicative plan on the (...) speaker's part that motivates the grammatical and usage properties of the construction where grammar alone cannot. The final section of the article presents corpus examples showing that Locative Inversion is indeed used in the contexts predicted by the plan associated with the construction. This result is both theoretically and methodologically significant, insofar as it constitutes a case where the grammatical properties of a syntactic construction are better explained through its typical conditions of use than through grammatical means proper. (shrink)

In case-marking languages with nominative-accusative alignment the subject of a sentence is usually marked by nominative case. In some of these languages, however, the subject of a number of verbs is either consistently or alternately marked by another, non-nominative case. Such non-canonical case marking has often been approached in the linguistic literature as a phenomenon at the interface between syntax and semantics. Yet the predictions of this kind of approach seem more probabilistic than regular. This paper offers a new (...) perspective to analyse the phenomenon, which encompasses the role of information structure in case marking. Drawing onSilverstein’s (1976)theory of differential subject marking andDalrymple & Nikolaeva’s (2011)approach to differential object marking, it is argued that non-canonically case-marked subjects can be better analysed as instances of either non-topical subjects or subjects lacking one or more semantic features typical of topicality. The approach outlined in the paper is tested on a number of constructions in Russian and Lithuanian. It is shown how, in both languages, the analysed instances of non-canonically case-marked subjects exhibit a complex interplay among grammatical, semantic and discourse-pragmatic factors. (shrink)

Canonical economic agents act so as to maximize a single, representative, utility function. However, there is accumulating evidence that heterogeneity in thought processes may be an important determinant of individual behavior. This paper investigates the implications of a vector-valued generalization of the Expected Utility paradigm, which permits agents either to deliberate as per Homo economics, or to act impulsively. This generalized decision theory is applied to explain the crowding-out effect, irrational educational investment decisions, persistent social inequalities, the pervasive influence (...) of non-cognitive ability on socio-economic outcomes, and the dynamic relationships between non-cognitive ability, cognitive ability, and behavioral biases. These results suggest that the generalized decision theory warrants further investigation. (shrink)