All the typical global quantum mechanical observables are complex relative phases obtained by interference phenomena. They are described by means of some global geometric phase factor, which is thought of as the “memory” of a quantum system undergoing a “cyclic evolution” after coming back to its original physical state. The origin of a geometric phase factor can be traced to the local phase invariance of the transition probability assignment in quantum mechanics. Beyond this invariance, transition probabilities also remain invariant under (...) the operation of complex conjugation. Most important, geometric phase factors distinguish between unitary and antiunitary transformations in terms of complex conjugation. These two types of invariance functions as an anchor point to investigate the role of loops and based loops in the state space of a quantum system as well as their links and interrelations. We show that arbitrary transition probabilities can be calculated using projective invariants of loops in the space of rays. The case of the double slit experiment serves as a model for this purpose. We also represent the action of one-parameter unitary groups in terms of oppositely oriented-based loops at a fixed ray. In this context, we explain the relation among observables, local Boolean frames of projectors, and one-parameter unitary groups. Next, we exploit the non-commutative group structure of oriented-based loops in 3-d space and demonstrate that it carries the topological semantics of a Borromean link. Finally, we prove that there exists a representation of this group structure in terms of one-parameter unitary groups that realizes the topological linking properties of the Borromean link. (shrink)

Cohesin is a ring‐shaped complex that is loaded on DNA in two different conformations. In one conformation, it forms loops to organize the interphase genome; in the other, it topologically encircles sibling chromosomes to facilitate homologous recombination and to establish the cohesion that is required for orderly segregation during mitosis. How, and even if, these two loading conformation are related is unclear. Here, I propose that loop binding is a required first step for topological binding. This loop‐binding‐first model (...) integrates the known information about the two loading mechanisms, explains genetic requirements for the two and explains how topological loading evolved from loop binding. (shrink)

The nuclear DNA of eukaryotes is organized into a series of loops each topologically anchored by elements of the nuclear matrix. Evidence is reviewed which indicates that the anchorage points of the loops are formed by transcriptionally active genes and that individual loops function as replicons. The data suggests a specific model for coupling of DNA replication and transcription in eukaryotes.

Since its discovery in 1959 the Aharonov-Bohm effect has continuously been the cause for controversial discussions of various topics in modern physics, e.g. the reality of gauge potentials, topological effects and nonlocalities. In the present paper we juxtapose the two rival interpretations of the Aharonov-Bohm effect. We show that the conception of nonlocality encountered in the Aharonov-Bohm effect is closely related to the nonseparability which is common in quantum mechanics albeit distinct from it due to its topological nature. We propose (...) a third alternative interpretation based on the loop space of holonomies which serves to solve some of the problems and we trace back the topological nonlocality and thereby the Aharonov-Bohm effect to their quantum mechanical origin. All three discussed interpretations are, of course, empirically equivalent. In fact, they present us with an instructive case study for the thesis of theory underdetermination by empirical data. (shrink)

This essay stages a dialectical confrontation between Adorno–Horkheimer on one hand and Benjamin–Badiou on the other against the background of the former's reductive portrait of Ulysses in Dialectic of the Enlightenment, which depicts him as a proto-bourgeois archetype of profit-seeking and acquisitive ethos. In sharp contrast, Walter Benjamin's allegorical materialism foregrounds, by dialectical illumination, hieroglyphic traces of Homeric virtues. These, I argue, are sustained and further amplified by Alain Badiou's topological ethics and loop-politics.

The organization of the genome into topologically associated domains (TADs) appears to be a fundamental process occurring across a wide range of eukaryote organisms, and it likely plays an important role in providing an architectural foundation for gene regulation. Initial studies emphasized the remarkable parallels between TAD organization in organisms as diverse as Drosophila and mammals. However, whereas CCCTC‐binding factor (CTCF)/cohesin loop extrusion is emerging as a key mechanism for the formation of mammalian topological domains, the genome organization in (...) Drosophila appears to depend primarily on the partitioning of chromatin state domains. Recent work suggesting a fundamental conserved role of chromatin state in building domain architecture is discussed and insights into genome organization from recent studies in Drosophila are considered. (shrink)

Gene transcription in eukaryotes is associated with conformational changes of a large area of chromatin adjacent to a gene. This rearrangement may involve the whole loop (topological domain) to which a given gene belongs.Regulatory events associated with activation or inactivation of transcription are found to act through relatively short nucleotide sequences, often located several thousand base pairs apart from gene. These sequences, termed enhancers may act independently on their distance from or orientation with respect to the gene.Both long‐range conformational (...) rearrangements of chromatin and any long distance effects of enhancers may be associated with elastic torsional strain in DNA, arising in transcriptionally active chromatin loops. Enhancer effects, in particular, may be associated with conformational transitions in DNA competing for the energy deposited in the elastic spring of the DNA. (shrink)

Topologically associating domain (TAD) boundaries are the flanking edges of TADs, also known as insulated neighborhoods, within the 3D structure of genomes. A prominent feature of TAD boundaries in mammalian genomes is the enrichment of clustered CTCF sites often with mixed orientations, which can either block or facilitate enhancer–promoter (E‐P) interactions within or across distinct TADs, respectively. We will discuss recent progress in the understanding of fundamental organizing principles of the clustered CTCF insulator codes at TAD boundaries. Specifically, both inward‐ (...) and outward‐oriented CTCF sites function as topological chromatin insulators by asymmetrically blocking improper TAD‐boundary‐crossing cohesin loop extrusion. In addition, boundary stacking and enhancer clustering facilitate long‐distance E‐P interactions across multiple TADs. Finally, we provide a unified mechanism for RNA‐mediated TAD boundary function via R‐loop formation for both insulation and facilitation. This mechanism of TAD boundary formation and insulation has interesting implications not only on how the 3D genome folds in the Euclidean nuclear space but also on how the specificity of E‐P interactions is developmentally regulated. (shrink)

We present a reformulation of loop quantum gravity with a cosmological constant and no matter as a Fermi-liquid theory. When the topological sector is deformed and large gauge symmetry is broken, we show that the Chern–Simons state reduces to Jacobson’s degenerate sector describing 1+1 dimensional propagating fermions with nonlocal interactions. The Hamiltonian admits a dual description which we realize in the simple BCS model of superconductivity. On one hand, Cooper pairs are interpreted as wormhole correlations at the de Sitter (...) horizon; their number yields the de Sitter entropy. On the other hand, BCS is mapped into a deformed conformal field theory reproducing the structure of quantum spin networks. When area measurements are performed, Cooper-pair insertions are activated on those edges of the spin network intersecting the given area, thus providing a description of quantum measurements in terms of excitations of a Fermi sea to superconducting levels. The cosmological constant problem is naturally addressed as a nonperturbative mass-gap effect of the true Fermi-liquid vacuum. (shrink)

Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture -based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, (...) some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. Single-cell Hi-C expands the molecular biology toolbox for studies of chromatin structure in individual cells. This technique allows one to analyze cell-to-cell variability in TAD and loop structure, and to capture chromosome conformation in rare cell types such as oocytes, totipotent cells, and tumor progenitors. (shrink)

Recent advances in genomic and imaging techniques have revealed the complex manner of organizing billions of base pairs of DNA necessary for maintaining their functionality and ensuring the proper expression of genetic information. The SMC proteins and cohesin complex primarily contribute to forming higher‐order chromatin structures, such as chromosomal territories, compartments, topologically associating domains (TADs) and chromatin loops anchored by CCCTC‐binding factor (CTCF) protein or other genome organizers. Cohesin plays a fundamental role in chromatin organization, gene expression and regulation. This (...) review aims to describe the current understanding of the dynamic nature of the cohesin‐DNA complex and its dependence on cohesin for genome maintenance. We discuss the current 3C technique and numerous bioinformatics pipelines used to comprehend structural genomics and epigenetics focusing on the analysis of Cohesin‐centred interactions. We also incorporate our present comprehension of Loop Extrusion (LE) and insights from stochastic modelling. (shrink)

Mereotopology is the discipline obtained from combining topology with the formal study of parts and their relation to wholes, or mereology. This article develops a mereotopological theory of time, illustrating how different temporal topologies can be effectively discriminated on this basis. Specifically, we demonstrate how the three principal types of temporal models—namely, the linear ones, the forking ones, and the circular ones—can be characterized by differently combining two sole mereotopological constraints: one to denote the absence of closed loops, and (...) the other one to denote the absence of branches. (shrink)

TAD boundaries are genomic elements that separate biological processes in neighboring domains by blocking DNA loops that are formed through Cohesin‐mediated loop extrusion. Most TAD boundaries consist of arrays of binding sites for the CTCF protein, whose interaction with the Cohesin complex blocks loop extrusion. TAD boundaries are not fully impermeable though and allow a limited amount of inter‐TAD loop formation. Based on the reanalysis of Nano‐C data, a multicontact Chromosome Conformation Capture assay, we propose a model (...) whereby clustered CTCF binding sites promote the successive stalling of Cohesin and subsequent dissociation from the chromatin. A fraction of Cohesin nonetheless achieves boundary read‐through. Due to a constant rate of Cohesin dissociation elsewhere in the genome, the maximum length of inter‐TAD loops is restricted though. We speculate that the DNA‐encoded organization of stalling sites regulates TAD boundary permeability and discuss implications for enhancer–promoter loop formation and other genomic processes. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Complex Mimetic SystemsHans Weigand (bio)The goal of science is to make the wonderful and complex understandable and simple—but not less wonderful.—Herb Simon, The Sciences of the Artificial11. IntroductionComplex systems theory stands for an approach in the social as well as natural and computational sciences that studies how interactions between parts give rise to collective behaviors of a system, and how the system interacts and forms relationships with its environment. (...) A typical example is the market economy, in which the order is emergent: it is the result of human action, but not the execution of any human design.2 Complex systems theory is currently a popular vehicle for understanding the complexities of the Internet; other examples of its application are as diverse as the stock market, ant colonies, epidemics, and the spread of business innovations. The focus in this article is on modeling social systems rather than physical or biological phenomena. [End Page 63]The mimetic theory developed by René Girard fits well with a systems perspective, as it has specific ideas about the drivers of human action (at the micro level) and cultural processes (at the macro level). The relationship has been explored earlier in several books and articles;3 in particular, in the work of the Centre de Recherche en Epistémologie Appliquée (CREA) in Paris. The systems perspective received a new stimulus in the 1990s in the form of complex adaptive systems (CAS),4 not least because of the agent-based computer simulations adopted at that time. The objective of this article is to introduce a special version of CAS, called complex mimetic systems (CMS), which builds on mimetic theory. The purpose of this article is twofold. On the one hand, the phrasing of mimetic theory in terms of CMS poses an interesting challenge to the theory to formalize its concepts and explicate possible limitations. On the other hand, CMS might be a useful contribution to the CAS field, as it incorporates concepts such as “social influence” that are very basic to but typically not spelled out in current CAS work.The structure of this article is as follows. In section 2, I briefly review the CAS literature and introduce the idea of complex mimetic systems. Section 3 describes a straw-man agent architecture for CMS, whereas in section 4, I move to the macro level and formalize the culture reproduction cycle. To illustrate the applicability of the CMS framework, I discuss in section 5 Ingo Piepers’s recent CAS analysis of the European international system in the period 1490–1945, and comment on it from a CMS perspective.2. Complex Mimetic SystemsThe characteristic features of complex systems are as follows:• Nonlinear effects: a small perturbation may have a large effect.• Feedback loops: the effects of an element’s behavior are fed back to it in some way. The feedback can be positive (amplification, runaway) or negative (damping).• Openness: a typical complex system interacts with its environment.• Memory: the history of a complex system may be important. Prior states may have an influence on present states.• Nesting, hierarchy: a complex system may itself be an element of a larger complex system. For example, clans in a tribal society, nation-states in an international system, or divisions in a company. [End Page 64]• Topology: the interactions of the elements are enabled and constrained by the network, or grid, of relationships between them.Complex Adaptive SystemsComplex adaptive systems (CAS) are a modern variant of complex systems theory. The elements of a complex adaptive system are called agents, as CAS builds on computational research in the field of multiagent systems.5 Although there is not much difference in the overall objectives, the use of agent simulation opens up interesting research opportunities. Let me clarify this by means of an introductory example given by Miller and Page, the standing ovation problem.6Standing ovations, in which waves of audience members stand up to express their particular appreciation of a performance, usually arise and evolve spontaneously. Suppose that we want to model this phenomenon. A starting point could be a simple mathematical model in which we distinguish N people, each receiving a signal... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:diacritics 35.1 (2005) 99-118MuseSearchJournalsThis JournalContents[Access article in PDF]Klossowski's AlternativePeter CanningThe sympathy that binds friends together into an extended family (a socius or community of allies), countering the impulse to tear each other apart, stops at the gate where the stranger is received with courtesy or turned away. Is it safe to let the other in, past the frontier of my territory, my extended Self? An ancient Greek proverb says (...) that "a friend is a second self"—which echoes the reversible sense of the word guest in ancient Indo-European languages (*hosti-pets-, "guest-master"), which continues into modern French hôte, "host" or "guest." This reciprocity actualizes the inclusive "or": one is guest or host in a reciprocal relation of hospitality. The friend is another self in that each becomes master of the other's house when received by the other as guest. Nor is the relation of hospitality limited to friendship; for according to an archaic tradition the Other, the "stranger sent from god" (as Homer says) is also to be received as guest-master of one's house.These are mythic and etymological conditions, probably idealized and in any case obsolete—what does the archaic institution of hospitality (supposing it was ever practiced in its ideal form) have to do with the crisis of social relation today?In what follows I propose an extended Klossowskian response to this question. But as a preliminary abbreviation let us turn the question around: is any social relation, today or any other day, even possible without passing through—or holding open—the moment of hospitality, of reception of the other, friend or stranger?When I let the other cross my threshold and penetrate the precinct of my home, my family, my own and proper extension of Self, when I give him my friendship and trust, it is then he becomes dangerous to me.1 Menelaus gave Paris his trust as an honored guest, whereupon his guest-friend abducted his wife, instigating the Trojan War.What is the psychic situation conditioned by receiving the other inside my Self? Taken literally, topologically, it is that the other as stranger becomes a part of me, inside me, that is, outside my control. What is inside and what is out, who is me and who is not-me? What and where is the psyche; what is its topology? Does it have an interior and exterior separated by a border between? "To see in the human soul a place [lieu, locus]—no longer to regard the human person otherwise than cohabited by the powers that can take possession of it: exterior powers, autonomous, those evoked by the Gospel—the ornate house that awaits the visit of demons and which, visited, is the parable [End Page 99] of the soul of each among us; this mental topology... the pathos itself [being] only a topos" [Monnoyer 35].Psyche and home are not only analogous or parabolic but the same situation, the same structure. Hospitality is a practice of that patho-logical identity, and a parable of psyche as locus of the Other.* * *Preliminary to entering further into this topic, it is necessary to raise another Klossowskian problem, of equal urgency (and intersecting that of hospitality): the place of perversion.Rather than take space to justify Klossowski's numerous equivocal apologias for the "singular case" of Sade (or Nietzsche),2 theorist of perversion, rhetorician, metteur en scène anxious to infect others with his unspeakable visions (demonic forms of perversion itself) and provoke them to institute the secret cult and practice of his theories—let us take up directly the matter of a definition: what is perversion? More to the point: what is its logic?Freud derives perversion from narcissism: to take one's own body as the object of the drive (or as object of desire), that is, as the object of eros and thanatos, self-love and self-destruction. But all drive passes by way of this loop from the body to itself—to the point that it becomes a question of how one is ever to get... (shrink)

This book is a treatise on time and on background independence in physics. It first considers how time is conceived of in each accepted paradigm of physics: Newtonian, special relativity, quantum mechanics (QM) and general relativity (GR). Substantial differences are moreover uncovered between what is meant by time in QM and in GR. These differences jointly source the Problem of Time: Nine interlinked facets which arise upon attempting concurrent treatment of the QM and GR paradigms, as is required in particular (...) for a background independent theory of quantum gravity. A sizeable proportion of current quantum gravity programs - e.g. geometrodynamical and loop quantum gravity approaches to quantum GR, quantum cosmology, supergravity and M-theory - are background independent in this sense. This book's foundational topic is thus furthermore of practical relevance in the ongoing development of quantum gravity programs. This book shows moreover that eight of the nine facets of the Problem of Time already occur upon entertaining background independence in classical (rather than quantum) physics. By this development, and interpreting shape theory as modelling background independence, this book further establishes background independence as a field of study. Background independent mechanics, as well as minisuperspace (spatially homogeneous) models of GR and perturbations thereabout are used to illustrate these points. As hitherto formulated, the different facets of the Problem of Time greatly interfere with each others' attempted resolutions. This book explains how, none the less, a local resolution of the Problem of Time can be arrived at after various reconceptualizations of the facets and reformulations of their mathematical implementation. Self-contained appendices on mathematical methods for basic and foundational quantum gravity are included. Finally, this book outlines how supergravity is refreshingly different from GR as a realization of background independence, and what background independence entails at the topological level and beyond. (shrink)

An original quantum foundations concept of a deep learning computational Universe is introduced. The fundamental information of the Universe (or Triuniverse)is postulated to evolve about itself in a Red, Green and Blue (RGB) tricoloured stable self-mutuality in three information processing loops. The colour is a non-optical information label. The information processing loops form a feedback-reinforced deep learning macrocycle with trefoil knot topology. Fundamental information processing is driven by ψ-Epistemic Drive, the Natural appetite for information selected for advantageous knowledge. From (...) its substrate of Mathematics, the knotted information processing loops determine emergent Physics and thence the evolution of super-emergent Life (biological and artificial intelligence). RGB-tricoloured information is processed in sequence in an Elemental feedback loop (R), then an Operational feedback loop (G), then a Structural feedback loop (B) and back to an Elemental feedback loop (R), and so on around the trefoil in deep learning macrocycles. It is postulated that hierarchical information correspondence from Mathematics through Physics to Life is mapped and conserved within each colour. The substrate of Mathematics has RGB-tricoloured feedback loops which are respectively Algebra (R), Algorithms (G) and Geometry (B). In Mathematics, the trefoil macrocycle is Algebraic Algorithmic Geometry and its correlation system is a Tensor Neural Knot Network enabling Qutrit Entanglement. Emergent Physics has corresponding RGB-tricoloured feedback loops of Quantum Mechanics (R), Quantum Deep Learning (G) and Quantum Geometrodynamics(B). In Physics, the trefoil macrocycle is Quantum Intelligent Geometrodynamics and its correlation system is Quantum Darwinism. Super-emergent Life has corresponding RGB-tricoloured loops of Variation (R), Selection (G) and Heredity (B). In the evolution of Life, the trefoil macrocycle is Variational Selective Heredity and its correlation ecosystem is Darwin’s ecologically “Entangled Bank”. (shrink)

Network motifs are small patterns of connections, found over‐represented in gene regulatory networks. An example is the negative feedback loop (e.g. factor A represses itself). This opposes its own state so that when ‘on’ it tends towards ‘off’ – and vice versa. Here, we argue that such self‐opposition, if considered dimensionlessly, is analogous to the liar paradox: ‘This statement is false’. When ‘true’ it implies ‘false’ – and vice versa. Such logical constructs have provided philosophical consternation for over 2000 (...) years. Extending the analogy, other network topologies give strikingly varying outputs over different dimensions. For example, the motif ‘A activates B and A. B inhibits A’ can give switches or oscillators with time only, or can lead to Turing‐type patterns with both space and time (spots, stripes or waves). It is argued here that the dimensionless form reduces to a variant of ‘The following statement is true. The preceding statement is false’. Thus, merely having a static topological description of a gene network can lead to a liar paradox. Network diagrams are only snapshots of dynamic biological processes and apparent paradoxes can reveal important biological mechanisms that are far from paradoxical when considered explicitly in time and space. (shrink)

The ideal scalar Aharonov–Bohm (SAB) and Aharonov–Casher (AC) effect involve a magnetic dipole pointing in a certain fixed direction: along a purely time dependent magnetic field in the SAB case and perpendicular to a planar static electric field in the AC case. We extend these effects to arbitrary direction of the magnetic dipole. The precise conditions for having nondispersive precession and interference effects in these generalized set ups are delineated both classically and quantally. Under these conditions the dipole is affected (...) by a nonvanishing torque that causes pure precession around the directions defined by the ideal set ups. It is shown that the precession angles are in the quantal case linearly related to the ideal phase differences, and that the nonideal phase differences are nonlinearly related to the ideal phase differences. It is argued that the latter nonlinearity is due to the appearance of a geometric phase associated with the nontrivial spin path. It is further demonstrated that the spatial force vanishes in all cases except in the classical treatment of the nonideal AC set up, where the occurring force has to be compensated by the experimental arrangement. Finally, for a closed space-time loop the local precession effects can be inferred from the interference pattern characterized by the nonideal phase differences and the visibilities. It is argued that this makes it natural to regard SAB and AC as essentially local and nontopological effects. (shrink)

Enhancers are short segments of regulatory DNA that control when and in which cell‐type genes should be turned on in response to a variety of extrinsic and intrinsic signals. At the molecular level, enhancers serve as a genomic scaffold that recruits sequence‐specific transcription factors and co‐activators to facilitate transcription from linked promoters. However, it remains largely unclear how enhancers communicate with appropriate target promoters in the context of higher‐order genome topology. In this review, we discuss recent progress in our (...) understanding of the functional interplay between enhancers, genome topology, and the molecular properties of transcription machineries in gene regulation. We suggest that the activities of transcription hubs are highly regulated through the dynamic rearrangement of enhancer‐promoter and promoter‐promoter connectivity during animal development. (shrink)

Undoubtedly the Penrose-Hameroff Orch OR model may be considered as a good theory for describing information processing mechanisms and holistic phenomena in the human brain, but it doesn’t give us satisfactory explanation of human perception. In this work a new approach explaining our perception is introduced, which is in good agreement with Orch OR model and other mainstream science theories such as string theory, loop quantum gravity and holographic principle. It is shown that human perception cannot be explained in (...) the terms of elementary particles and we should introduce new indivisible holistic objects with geometry based on smooth infinitesimal analysis - elastic membranes. The example of such a membrane is our Universe which is an indivisible whole. It is shown that our perception may be considered as the result of elastic oscillations of two dimensional (2D) elastic membranes with closed topology embedded in our bodies. Only one elastic membrane responsible for its perceptions will correspond to the selected organism, but there may be other membranes, even at the cell level. In other words, reality may be considered as the process of time evolution of holistic energetically very weak macro objects - elastic membranes with the geometry based on smooth infinitesimal analysis. An embedded membrane in this multidimensional world will look different for the external and internal observers: from the outside it will look like a material object with smooth infinitesimal geometry, while from the inside our Universe-like space-time fabric. When interacting with elementary particles and other membranes, a membrane will transform their energy into its elastic energy (a new form of energy) - the energy of stretching of the infinitesimal segments. The theory postulates that these elastic deformations will not be observable from the point of view of the internal observer. Heisenberg’s uncertainty principle will work in this physics only from the point of view of the internal observer. For the external observer each embedded elastic membrane may be stretched and even a very small region will become observable. For example, living organisms play the role of internal observers of the Universe, and at the same time they serve as external observers for 2D membranes embedded into our Universe. We can observe our 2D self-membranes through our perceptions, which are encoded in elastic oscillations of the elastic membrane. According to the theory, elastic membranes occupy energetically favorable positions around microtubules involved into Orch OR. The theory not only gives us a really multidimensional holistic picture of reality, but it also provides us with a new method for understanding such phenomena as perception, self-awareness and will. (shrink)

Recent systematic studies using newly developed genomic approaches have revealed common mechanisms and principles that underpin the spatial organization of eukaryotic genomes and allow them to respond and adapt to diverse functional demands. Genomes harbor, interpret, and propagate genetic and epigenetic information, and the three‐dimensional (3D) organization of genomes in the nucleus should be intrinsically linked to their biological functions. However, our understanding of the mechanisms underlying both the topological organization of genomes and the various nuclear processes is still largely (...) incomplete. In this essay, we focus on the functional relevance as well as the biophysical properties of common organizational themes in genomes (e.g. looping, clustering, compartmentalization, and dynamics), and examine the interconnection between genome structure and function from this angle. Present evidence supports the idea that, in general, genome architecture reflects and influences genome function, and is relatively stable. However, the answer as to whether genome architecture is a hallmark of cell identity remains elusive. (shrink)

There are possible worlds in which time is circular and finite in duration, forming a loop of, say, 12,000 years. There are also possible worlds in which time is linear and infinite in both directions and in which history is repetitive, consisting of infinitely many 12,000-year epochs, each two of which are exactly alike with respect to all intrinsic, purely qualitative properties. Could one ever have empirical evidence that one inhabits a world of the first kind rather than a (...) world of the second kind? We argue for the affirmative answer, contra Quine, Newton-Smith, and Bergström. Our argument for that conclusion differs from an argument for the same conclusion due to Weir. Weir’s argument is probabilistic and explicitly requires having evidence against determinism. Our argument is a direct appeal to the simplicity of laws, and it involves no probabilistic component. It is modeled on Shoemaker’s argument that one could have evidence of time without change. (shrink)

Literacy is an essential skill. Learning to read is a requirement for becoming a self-providing human being. However, while spoken language is acquired naturally with exposure to language without explicit instruction, reading and writing need to be taught explicitly. Decades of research have shown that well-structured teaching of phonological awareness, letter knowledge, and letter-to-sound mapping is crucial in building solid foundations for the acquisition of reading. During the COVID-19 pandemic, children worldwide did not have access to consistent and structured teaching (...) and are, as a consequence, predicted to be behind in the development of their reading skills. Subsequent evidence confirms this prediction. With the best evidence-based practice in mind, we developed an online version of a well-structured early literacy training program for 5-year-old children. This 2-week online Reading Camp program is designed for pre-K children. It incorporates critical components of the fundamental skills essential to learning to read and is taught online in an interactive, multi-sensory, and peer-learning environment. We measure the participants’ literacy skills and other related skills before and after participating in the online Reading Camp and compare the results to no-treatment controls. Results show that children who participated in the online Reading Camp improved significantly on all parameters in relation to controls. Our results demonstrate that a well-structured evidence-based reading instruction program, even if online and short-term, benefits 5-year-old children in learning to read. With the potential to scale up this online program, the evidence presented here, alongside previous evidence for the efficacy of the in-person program, indicates that the online Reading Camp program is effective and can be used to tackle a variety of questions regarding structural and functional plasticity in the early stages of reading acquisition. (shrink)

In recent years, a number of philosophers have conducted empirical studies that survey people's intuitions about various subject matters in philosophy. Some have found that intuitions vary accordingly to seemingly irrelevant facts: facts about who is considering the hypothetical case, the presence or absence of certain kinds of content, or the context in which the hypothetical case is being considered. Our research applies this experimental philosophical methodology to Judith Jarvis Thomson's famous Loop Case, which she used to call into (...) question the validity of the intuitively plausible Doctrine of Double Effect. We found that intuitions about the Loop Case vary according to the context in which the case is considered. We contend that this undermines the supposed evidential status of intuitions about the Loop Case. We conclude by considering the implications of our findings for philosophers who rely on the Loop Case to make philosophical arguments and for philosophers who use intuitions in general. (shrink)

Salloch and Eriksen (2024) present a compelling case for including patients as co-reasoners in medical decision-making involving artificial intelligence (AI). Drawing on O'Neill’s neo-Kantian frame...

We focus on a neglected aspect of scientific theory choice: how the selection of theories affects epistemic values. Building on Kuhn, we provide a general characterization of the feedback-loop dynamic between theories and values in theory choice as analogous to the relationship between organisms and the environment in niche construction. We argue that understanding theory choice as niche construction can explain how certain values acquire more weight and a specific application over time, and how resistance to scientific change can, (...) therefore, arise. We illustrate our picture by looking at the Mendelian–biometrician controversy. (shrink)

This paper is a culmination of our new foundations for recursive analysis through recursive topology as reported in Kalantari and Welch 125; 98 87). While in those papers we developed groundwork for an approach to point free analysis and applied recursion theory, in this paper we blend techniques of recursion theory with those of topology to establish new findings. We present several new techniques different from existing ones which yield interesting results. Incidental to our work is a unifying (...) explanation of various schools of study for recursive analysis. (shrink)

An axiomatic development of the theory of apartness and nearness of a point and a set is introduced as a framework for constructive topology. Various notions of continuity of mappings between apartness spaces are compared; the constructive independence of one of the axioms from the others is demonstrated; and the product apartness structure is defined and analysed.

The human-centered AI approach posits a future in which the work done by humans and machines will become ever more interactive and integrated. This article takes human-centered AI one step further. It argues that the integration of human and machine intelligence is achievable only if human organizations—not just individual human workers—are kept “in the loop.” We support this argument with evidence of two case studies in the area of predictive maintenance, by which we show how organizational practices are needed (...) and shape the use of AI/ML. Specifically, organizational processes and outputs such as decision-making workflows, etc. directly influence how AI/ML affects the workplace, and they are crucial for answering our first and second research questions, which address the pre-conditions for keeping humans in the loop and for supporting continuous and reliable functioning of AI-based socio-technical processes. From the empirical cases, we extrapolate a concept of “keeping the organization in the loop” that integrates four different kinds of loops: AI use, AI customization, AI-supported original tasks, and taking contextual changes into account. The analysis culminates in a systematic framework of keeping the organization in the loop look based on interacting organizational practices. (shrink)

In their article “What are Humans Doing in the Loop? Co-Reasoning and Practical Judgment When Using Machine Learning-Driven Decision Aids,” Salloch and Eriksen (2024) propose involving patients as...

This is the first, out of two papers, devoted to Andrzej Grzegorczyk’s point-free system of topology from Grzegorczyk :228–235, 1960. https://doi.org/10.1007/BF00485101). His system was one of the very first fully fledged axiomatizations of topology based on the notions of region, parthood and separation. Its peculiar and interesting feature is the definition of point, whose intention is to grasp our geometrical intuitions of points as systems of shrinking regions of space. In this part we analyze separation structures and Grzegorczyk (...) structures, and establish their properties which will be useful in the sequel. We prove that in the class of Urysohn spaces with countable chain condition, to every topologically interpreted representative of a point in the sense of Grzegorczyk’s corresponds exactly one point of a space. We also demonstrate that Tychonoff first-countable spaces give rise to complete Grzegorczyk structures. The results established below will be used in the second part devoted to points and topological spaces. (shrink)

This essay critically develops Watsuji’s nondual ontology of the self. Watsuji shows that the self is constituted by its relational contact with others and by its immersion in a wider geo-cultural environment. Yet Watsuji himself had difficulty in smoothly bringing together and integrating these notions. By showing how these domains work together to constitute the self, I bring into view the unity at the ground of Watsuji’s thought and the implications of this account for key ideas in Heidegger’s philosophy and (...) for environmental ethics. (shrink)

The problem of developing research and innovation in accordance with society’s general needs and values has received increasing attention in research policy. In the last 7 years, the concept of “Responsible Research and Innovation” has gained prominence in this regard, along with the resulting question of how best to integrate awareness about science–society relations into daily practices in research and higher education. In this context, post-graduate training has been seen as a promising entrance point, but tool-kit approaches more frequently have (...) been used. In this paper, we present and analyze an experiment—in the format of a Ph.D. course for early-career researchers—deploying an alternative approach. Drawing on Argyris and Schön’s framing of reflective practice, and their distinctions between espoused theories and theories-in-use, the analyzed course endeavored to stimulate double-loop learning. Focusing on dislocatory moments, this paper analyses how the course tried to teach participants to reflect upon their own practices, values, and ontologies, and whether this provided them with the resources necessary to reflect on their theories-in-use in their daily practices. (shrink)

A sequence x=xn:nω of elements of a complete Boolean algebra converges to a priori if lim infx=lim supx=b. The sequential topology τs on is the maximal topology on such that x→b implies x→τsb, where →τs denotes the convergence in the space — the a posteriori convergence. These two forms of convergence, as well as the properties of the sequential topology related to forcing, are investigated. So, the a posteriori convergence is described in terms of killing of tall (...) ideals on ω, and it is shown that the a posteriori convergence is equivalent to the a priori convergence iff forcing by does not produce new reals. A property of c.B.a.’s, satisfying -cc -cc and providing an explicit definition of the a posteriori convergence, is isolated. Finally, it is shown that, for an arbitrary c.B.a. , the space is sequentially compact iff the algebra has the property and does not produce independent reals by forcing, and that implies P is the unique sequentially compact c.B.a. in the class of Suslin forcing notions. (shrink)

This paper presents a novel fractional-order PID controller tuning strategy based on Bode’s optimal loop shaping which is commonly used for LTI feedback systems. Firstly, the controller parameters are achieved based on flat phase property and Bode’s optimal reference model, so that the controlled system is robust to gain variations and can achieve desirable transient performance according to various control requirements. Then, robustness analysis of the controlled system is carried out to support the results. Furthermore, the parameter setting is (...) analyzed to demonstrate the superiority of the proposed controller. At last, some simulation examples are shown to verify the accuracy and usefulness of the proposed control strategy. The proposed fractional-order PID controller does not have any restriction on the controlled plant, so it can be widely applied on both integer-order and fractional-order systems. (shrink)

This essay introduces this special issue on virtue ethics in relation to military AI. It describes the current situation of military AI ethics as following that of AI ethics in general, caught between consequentialism and deontology. Virtue ethics serves as an alternative that can address some of the weaknesses of these dominant forms of ethics. The essay describes how the articles in the issue exemplify the value of virtue-related approaches for these questions, before ending with thoughts for further research.