Is "the theory of everything'' merely the ultimate ensemble theory?

We discuss some physical consequences of what might be called ``the ultimate ensemble theory'', where not only worlds corresponding to say different sets of initial data or different physical constants are considered equally real, but also worlds ruled by altogether different equations. The only postulate in this theory is that all structures that exist mathematically exist also physically, by which we mean that in those complex enough to contain self-aware substructures (SASs), these SASs will subjectively perceive themselves as existing in a physically ``real'' world. We find that it is far from clear that this simple theory, which has no free parameters whatsoever, is observationally ruled out. The predictions of the theory take the form of probability distributions for the outcome of experiments, which makes it testable. In addition, it may be possible to rule it out by comparing its a priori predictions for the observable attributes of nature (the particle masses, the dimensionality of spacetime, etc) with what is observed.Comment: 29 pages, revised to match version published in Annals of Physics. The New Scientist article and color figures are available at http://www.sns.ias.edu/~max/toe_frames.html or from [email protected]

The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1

Aberrant DNA methylation is often associated with cancer and the formation of tumors; however, the underlying mechanisms, in particular the recruitment and regulation of DNA methyltransferases remain largely unknown. In this study, we identified USP7 as an interaction partner of Dnmt1 and UHRF1 in vivo. Dnmt1 and USP7 formed a soluble dimer complex that associated with UHRF1 as a trimeric complex on chromatin. Complex interactions were mediated by the C-terminal domain of USP7 with the TS-domain of Dnmt1, whereas the TRAF-domain of USP7 bound to the SRA-domain of UHRF1. USP7 was capable of targeting UHRF1 for deubiquitination and affects UHRF1 protein stability in vivo. Furthermore, Dnmt1, UHRF1 and USP7 co-localized on silenced, methylated genes in vivo. Strikingly, when analyzing the impact of UHRF1 and USP7 on Dnmt1-dependent DNA methylation, we found that USP7 stimulated both the maintenance and de novo DNA methylation activity of Dnmt1 in vitro. Therefore, we propose a dual role of USP7, regulating the protein turnover of UHRF1 and stimulating the enzymatic activity of Dnmt1 in vitro and in vivo

Using hypnosis to disrupt face processing: mirrored-self misidentification delusion and different visual media

Mirrored-self misidentification delusion is the belief that one’s reflection in the mirror is not oneself. This experiment used hypnotic suggestion to impair normal face processing in healthy participants and recreate key aspects of the delusion in the laboratory. From a pool of 439 participants, 22 high hypnotisable participants (“highs”) and 20 low hypnotisable participants were selected on the basis of their extreme scores on two separately administered measures of hypnotisability. These participants received a hypnotic induction and a suggestion for either impaired (i) self-face recognition or (ii) impaired recognition of all faces. Participants were tested on their ability to recognize themselves in a mirror and other visual media – including a photograph, live video, and handheld mirror – and their ability to recognize other people, including the experimenter and famous faces. Both suggestions produced impaired self-face recognition and recreated key aspects of the delusion in highs. However, only the suggestion for impaired other-face recognition disrupted recognition of other faces, albeit in a minority of highs. The findings confirm that hypnotic suggestion can disrupt face processing and recreate features of mirrored-self misidentification. The variability seen in participants’ responses also corresponds to the heterogeneity seen in clinical patients. An important direction for future research will be to examine sources of this variability within both clinical patients and the hypnotic model

Living God Pandeism: Evidential Support

Pandeism is the belief that God chose to wholly become our Universe, imposing principles at this Becoming that have fostered the lawful evolution of multifarious structures, including life and consciousness. This article describes and defends a particular form of pandeism: living God pandeism (LGP). On LGP, our Universe inherits all of God's unsurpassable attributes—reality, unity, consciousness, knowledge, intelligence, and effectiveness—and includes as much reality, conscious and unconscious, as is possible consistent with retaining those attributes. God and the Universe, together “God-and-Universe,” is also eternal into the future and the past. The article derives testable hypotheses from these claims and shows that the evidence to date confirms some of these while falsifying none. Theism cannot be tested in the same way

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Approche globale et harmonisée de la validation

National audienceThe goal of this communication is to describe how two fundamental requirements of ISO 17025 standard, i.e. validate methods and estimate the uncertainty of measurements, can give a way to check whether an analytical method is correctly “fi t its purpose”. Both these requirements are not independent and it will be shown how they can be combined A recent approach based on the “accuracy profi le” of a method was applied to the determination of vitamin B3 in milk by LC-fl uorimetry and illustrates how it can be applied for validating a method. Concentrations are expressed as mg/L and instrumental response is peak height. Experimental design namely consisted in preparing triplicate standard solutions at 3 concentration levels; this was repeated during 3 days. The validation experimental design was similar but consisted of spiked samples of two different milks.Le but de cette communication est de montrer comment deux exigences fondamentales de la norme ISO 17025, à savoir la validation des méthodes et l’estimation de l’incertitude, peuvent se rejoindre pour élaborer une procédure servant à vérifier si une méthode est bien adaptée à ses objectifs. Cette approche nouvelle, appelée profil d’exactitude, a été appliquée à une méthode HPLC-fluorimétrie de détermination de la vitamine B3 dans le lait. Les concentrations sont exprimées en mg/L et la réponse instrumentale en hauteur de pic. Le plan d’expérience d’étalonnage consistait à préparer en triple des solutions étalons à 3 niveaux de concentration et à les répéter sur 3 jours. Le plan d’expérience de validation avait la même structure mais a été réalisé par ajouts dosés dans 2 laits différents

Labo-Stat : Guide de validation des méthodes d’analyse

National audienceValider une méthode d'analyse consiste à apporter la preuve qu'elle est adaptée aux objectifs que l'on s'est fixé. Il ne suffit donc pas de calculer quelques critères de validation, tels que la répétabilité ou la justesse, il faut aussi interpréter les valeurs trouvées pour déboucher sur une conclusion claire et sans ambigüité. Pour atteindre cet objectif, Labo-Stat propose en avant-première une démarche raisonnée basée sur la méthode du profil d'exactitude. L'intérêt de cette nouvelle approche est de déboucher sur un mode d'interprétation graphique des résultats particulièrement parlant pour le non-statisticien. Cette méthode est actuellement l'objet de travaux de normalisation auxquels participe très activement l'auteur au sein de l'Afnor. Consacré à la conception et la conduite des études de validation des méthodes quantitatives d'analyse, Labo-Stat consiste en une présentation détaillée : des aspects expérimentaux pour une collecte optimisée des données, des méthodes statistiques nécessaires à leur traitement et interprétation, en soulignant les problèmes rencontrés avec les procédures classiques de validation, de la méthode du profil d'exactitude, cœur de l'ouvrage, où il est démontré avec des exemples à l'appui, que cette méthode n'est pas seulement un outil de décision mais aussi un outil de diagnostic révélant les défauts de la méthode, comme un problème de justesse ou une inadaptation aux objectifs recherchés. Dans ce guide très pratique une large part est faite aux applications numériques, sous la forme des feuilles de calcul modèles pour des tableurs (Microsoft Excel®, Open Office) ou de petits scripts utilisables dans l'environnement R accessibles en ligne. Un chapitre important est consacré à diverses applications couvrant des techniques d'analyses physicochimiques, comme la HPLC ou la spectrométrie, et des méthodes biologiques, comme ELISA ou la microbiologie. À travers ces exemples, divers problèmes classiques sont illustrés et les solutions pratiques expliquées. Labo-Stat s'avérera très utile aux techniciens et chercheurs des laboratoires d'analyse (biologie, pharmacie, agroalimentaire, analyse environnementale, chimie), aux ingénieurs (agronomes, biochimistes, chimistes...) et aux étudiants des IUT et des universités 2e et 3e cycles, écoles d'ingénieurs ou facultés de pharmacie..

Développements analytiques pour l’évaluation de la teneur en phytostérols des aliments : approche inter-laboratoires

A set of collaborative studies was carried out on 6 food items in order to determine their contents phytosterols. The interest of these studies is to make it possible to calculate a certain number of figures of merit for methods known as of reference methods. Finally, the calculation of the function of uncertainty for these methods shows that uncertainty remains high, especially for the weak concentrations, and that it must have a substantial influence on the evaluation of phytostérols intake. Similarly, it can be concluded that the analysis of phytosterols in foods remains a delicate operation which would deserve more attention from standardization bodies, especially in the current context of supplementation of certain foods

From method validation to result assessment: Established facts and pending questions

This paper aims to present a critical discussion of existing strategies to emphasize possible pitfalls and expected trends that arise from method validation to result assessment. It critically presents some aspects of the three main historical steps, namely terminology, method validation and quality of results. In addition to the formal link between method validation and measurement uncertainty that was recently demonstrated, the abundance of propositions also leads to some problems of consistency. Particular interest is given to the use of tolerance intervals as an appropriate tool to make decisions in method validation, control charts and determination of measurement uncertainty, considering various possibilities regarding adjustments of coverage percentage that can present difficulty for most analytical scientists