In a recent issue of Nature Communications Ukleja and co‐workers reported a cryo‐EM 3D reconstruction of the Ccr4‐Not complex from Schizosaccharomyces pombe with an immunolocalization of the different subunits. The newly gained architectural knowledge provides cues to apprehend the functional diversity of this major eukaryotic regulator. Indeed, in the cytoplasm alone, Ccr4‐Not regulates translational repression, decapping and deadenylation, and the Not module additionally plays a positive role in translation. The spatial distribution of the subunits within the structure is compatible with (...) a model proposing that the Ccr4‐Not complex interacts with the 5′ and 3′ ends of target mRNAs, allowing different functional modules of the complex to act at different stages of the translation process, possibly within a circular constellation of the mRNA. This work opens new avenues, and reveals important gaps in our understanding regarding structure and mode of function of the Ccr4‐Not complex that need to be addressed in the future. (shrink)

Nicotinic acetylcholine receptors (nAChRs) are ligand‐gated ion channels that bring about a diversity of fast synaptic actions. Analysis of the Caenorhabditis elegans genome has revealed one of the most‐extensive and diverse nAChR gene families known, consisting of at least 27 subunits. Striking variation with possible functional implications has been observed in normally conserved motifs at the acetylcholine‐binding site and in the channel‐lining region. Some nAChR subunits are particular to neurons whilst others are present in both neurons and muscles. The (...) class='Hi'>localization of subunits in non‐synaptic regions suggests novel roles for nAChRs. Genetic and heterologous expression studies have identified a subset of nAChR subunits that are important drug targets while the study of mutants has identified genes functionally‐linked to nAChRs. Future studies using C. elegans offer the prospect of increasing our understanding of the functional diversity of a complex nAChR gene family as well as addressing the role of nAChRs and associated proteins in human disorders. BioEssays 26:39–49, 2004.© 2003 Wiley Periodicals, Inc. (shrink)

An early step in sporulation of the bacterium Bacillus subtilis, is the formation of two compartments in the developing sporangium: the mother cell and the forespore. These compartments differ in their programs of gene expression and developmental fate. The establishment of cell type within this simple developmental program, is accomplished by the compartmentalization of sigma subunits of RNA polymerase. The localization of these sigma factors results in compartment‐specific gene expression. Recent experiments have elucidated some of the early steps in (...) the establishment of 3V cell type. After septum formation, the activity of the sigma factor, σF, is confined to the forespore compartment. This, in turn, results in the localized expression of another developmental sigma factor, σG. The forespore localization of these two sigma factors, establishes the forespore line of gene expression. σF and σG also regulate mother cell events. σF activity in the forespore regulates the proteolytic processing of σE within the mother cell compartment. The localization σE activity leads to mother cell expression of another sigma factor, pro‐σK The proteolytic processing of pro‐σK to mature σK is controlled by the forespore sigma factor, σG Mature σK then directs the transcription of mother cell specific genes. Therefore, the initial localization of σF activity to the forespore compartment, orchestrates the establishment of cell type in both forespore and mother cell compartments. (shrink)

In the vision of ubiquitous computing it should be possible to create situational and context-aware applications of the internet. But there is a conflict between the global claim of the system and the context-aware local application. First of all it must be clear, what context means. Is the context determined by the material local environment or by the special intention of a person’s action. What role do cultural factors with their historical implications and scales of value play? The meaning of (...) locality depends on the definition of the term context. Thus the term locality specifies an analogy to the term ‘context’. It is necessary especially to also clarify categories like “Leib” and “Lebenswelt”. Finally it is pointed out that special claims of ubiquitous computing like the idea of a global world-model are untenable. Though ubiquitous computing technologies are calm and invisible, it is important to make visible their components. The antagonism between localisation and globalisation shows the real potential of, as well as the claims of, ubiquitous computing. (shrink)

The article proposes systematisation and development of the discourse of the East European methodological traditions regarding application of the systematic approach as a way of subject localisation in psychological research. In particular, the author’s version of systematic localisation of psychological research subjects by means of structural and ontological visualisations has been developed. The procedure proposed for systematic localisation of the researched subject includes four subsequent stages: 1) fixation of the borders and structure of the ontological field which is being studied; (...) 2) segment analysis of the obtained structure; 3) study of specifics and contents of structural and functional ties; 4) visual mapping of genesis of the core processes. The article describes specifics of application of systematic localisation of the subject of research at the example of such researched object as personal socialisation. (shrink)

Nous abordons, dans cet article, le fonctionnement discursif des adverbiaux de localisation spatiale dehors et au dehors. Notre objectif est de mettre en valeur leur rôle dans la structuration du discours. Nous proposons aussi un examen des propriétés combinatoires et des conditions d’emploi de ces deux expressions dans les séquences narratives.. Nous montrerons enfin que, dans certains contextes, la valeur spatiale liée à l’emploi de ces adverbiaux peut être dédoublée d’une valeur temporelle.

L'Auteur confirme, par une révision de l'inventaire athénien ID, 1417, A, I, 1. 69-70, la localisation du Thesmophorion délien qu'il avait proposée BEG 99 (1986), p. 309-317, près du rivage Nord-Est de la calanque de Skardhana. Le sanctuaire est aujourd'hui, au moins en majeure partie, englouti. Une prospection sous-marine pourrait en retrouver des vestiges.

Given a cofinal cardinal function $h\in {}^{\kappa }\kappa $ for $\kappa $ inaccessible, we consider the dominating h-localisation number, that is, the least cardinality of a dominating set of h-slaloms such that every $\kappa $ -real is localised by a slalom in the dominating set. It was proved in [3] that the dominating localisation numbers can be consistently different for two functions h (the identity function and the power function). We will construct a $\kappa ^+$ -sized family of functions h (...) and their corresponding localisation numbers, and use a ${\leq }\kappa $ -supported product of a cofinality-preserving forcing to prove that any simultaneous assignment of these localisation numbers to cardinals above $\kappa $ is consistent. This answers an open question from [3]. (shrink)

In this journal, Bucci (2022) has argued that two famous experiments in the neuroscientific literature can be used to support property dualism about the mind. In what follows, I attempt to illustrate that those experiments are completely compatible with a naive identity mind-brain/body identity theory.

The central aim of this book is to understand modules and the categories they form through associated structures and dimensions, which reflect the complexity of these, and similar, categories.

We reimplement the creature forcing construction used by Fischer et al. :1045–1103, 2017. https://doi.org/10.1007/S00153-017-0553-8. arXiv:1402.0367 [math.LO]) to separate Cichoń’s diagram into five cardinals as a countable support product. Using the fact that it is of countable support, we augment our construction by adding uncountably many additional cardinal characteristics, sometimes referred to as localisation cardinals.

The analysis of demonstration locations classified by degree of urbanization shows that demonstrating is an urban phenomenon. Seldom are demonstrations held in thinly populated residential areas. A demonstration can thus be considered among the farms of political action for which the participation stimulating factors are clearly more present in urban areas than in rural areas.The distribution of the demonstrations over the regions indicates that more demonstrating is done in Flanders than in Wallonia. Flemings and 'walloons, moreover, appeared in the streets (...) for different points of confiict during the period from 1953 to 1974.Demonstrations with ideological themes overwhelmingly, and communitarian themes mostly, occurred in Flanders ; demonstrations for socioeconomic purposes occurred mostly in Wallonia. Demonstrations in the capital, Brussels, had the most participants on the average in general andalso for the three conflict areas. (shrink)

Ageing populations and rising rates of chronic disease globally have shifted key elements of disease management to ideas of integrated care and self‐management. The associated policies and programmes often focus on intervention and support beyond the sites of the hospital and clinic. These shifts have significantly impacted the delivery and practice of nursing for both nurses and the clients with whom they work. This article argues that Foucault's comments on space, place and heterotopia (1986) are useful in exploring these changes (...) from a philosophical perspective, to draw out the complexity of these programmes and add texture to discussions on the ways these shifts to localisation and the dominant discourses of self‐management and responsibility have reconfigured nursing practices. The theoretical discussion is augmented with illustrations from an Australian integrated health care programme. (shrink)

Spontaneous localization theories are a class of quantum theories which solve the so-called measurement problem by non-linearly and stochastically modifying the Schrödinger dynamics. In this paper I briefly explain where these theories are coming from, what their driving ideas and main features are, and how they were historically developed. Also, I discuss their empirical and ontological adequacy, as well as their relativistic extensions and their experimental confirmation.

Spontaneous localization theory is a quantum theory proposed by GianCarlo Ghirardi, together with Alberto Rimini and Tullio Weber in 1986. However, soon it became clear to Ghirardi that his work was more than just one theory: he actually developed a framework, a family of theories in which the wavefunction jumps, but where the ontology of the theory is underdetermined. After acknowledging that the wavefunction did not provide a satisfactory ontology, he assumed that matter was described by a continuous matter (...) density field in three-dimensional space, whose evolution is governed by a stochastic wavefunction evolution. Alternatively, Bell assumed that the wavefunction would govern a spatiotemporal event ontology, dubbed ‘flashes.’ However, not much work has been done with the perhaps most obvious possibility, namely that physical objects are made of particles. This paper has two aims. First to explain the reason why people require spontaneous localization theory to be more than just a theory about the wavefunction. This is done by showing how the problem everyone in the foundation of quantum mechanics take to be the fundamental problem of quantum mechanics, namely the measurement problem, is a red herring. Then, the paper explores the possibility of spontaneous localization theories of particles. I argue that this discussion is not a mere exercise, as spontaneous localization theories of particles may be amenable to a relativistic extension which does not require a foliation, and because in general the peculiar type of indeterminism of spontaneous localization theories may help shedding new light on the nature of the tension between quantum theory and relativity. (shrink)

Les noms centre et milieu sont des Noms de Localisation Interne pouvant se combiner avec la préposition à, et construire de la sorte des locutions prépositionnelles locatives NP0 au milieu de NP1 et NP0 au centre de NP1. Dans un cadre référentialiste, leur caractérisation s’appuie sur une représentation géométrique du sens de centre et de milieu. L’objectif de cet article est de remettre en question ce point de vue en montrant que la distinction entre au milieu de et au centre (...) de tient dans deux paramètres sémantiques : le caractère délimité ou non de NP1 et la signification fonctionnelle de NP0 par rapport à NP1. A l’aide de ces deux critères nous rendrons compte de données qui vont du domaine concret au domaine abstrait. L’étude de ces deux locutions est en outre un bon prétexte pour proposer une approche de la localisation qui s’inscrit dans un arrière-plan philosophique inhabituel, celui de la phénoménologie. Nous développerons l’idée que les effets de perspectives induits par les locutions au centre / milieu de ne se rapportent pas à une réalité commune, et que ce qui est localisé par une locution ne coïncide jamais avec ce qui est localisé par l’autre, même dans les cas d’apparente synonymie. Pour cela, nous reprendrons l’opposition gestaltiste figure / fond, et nous montrerons que au centre de établit une relation fonctionnelle avec un tout délimité, tandis que au milieu de établit un rapport de coïncidence avec un fond dont la délimitation n’est pas spécifiée. (shrink)

An analysis of two heuristic strategies for the development of mechanistic models, illustrated with historical examples from the life sciences. In Discovering Complexity, William Bechtel and Robert Richardson examine two heuristics that guided the development of mechanistic models in the life sciences: decomposition and localization. Drawing on historical cases from disciplines including cell biology, cognitive neuroscience, and genetics, they identify a number of "choice points" that life scientists confront in developing mechanistic explanations and show how different choices result in (...) divergent explanatory models. Describing decomposition as the attempt to differentiate functional and structural components of a system and localization as the assignment of responsibility for specific functions to specific structures, Bechtel and Richardson examine the usefulness of these heuristics as well as their fallibility—the sometimes false assumption underlying them that nature is significantly decomposable and hierarchically organized. When Discovering Complexity was originally published in 1993, few philosophers of science perceived the centrality of seeking mechanisms to explain phenomena in biology, relying instead on the model of nomological explanation advanced by the logical positivists (a model Bechtel and Richardson found to be utterly inapplicable to the examples from the life sciences in their study). Since then, mechanism and mechanistic explanation have become widely discussed. In a substantive new introduction to this MIT Press edition of their book, Bechtel and Richardson examine both philosophical and scientific developments in research on mechanistic models since 1993. (shrink)

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task.Methods: Twenty-five patients with pharmaco-resistant epilepsy, (...) including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects.Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and pari... (shrink)

Case studies in the psychophysics, modeling and localization of human vision are presented as an example of “hands-on” philosophy of the cognitive sciences. These studies also yield important results for familiar problems in philosophy of mind: the explanatory gap surrounding phenomenological feels is not closed by the kinds of investigations surveyed. However, the science is able to explain some sorts of phenomenological facts, such as why the human color space takes the form of the Munsell color solid, or why (...) there is a phenomenologically-pure yellow but not a phenomenologically-pure orange. (shrink)