Prediction and explanation in the multiverse

Probabilities in the multiverse can be calculated by assuming that we are typical representatives in a given reference class. But is this class well defined? What should be included in the ensemble in which we are supposed to be typical? There is a widespread belief that this question is inherently vague, and that there are various possible choices for the types of reference objects which should be counted in. Here we argue that the ``ideal'' reference class (for the purpose of making predictions) can be defined unambiguously in a rather precise way, as the set of all observers with identical information content. When the observers in a given class perform an experiment, the class branches into subclasses who learn different information from the outcome of that experiment. The probabilities for the different outcomes are defined as the relative numbers of observers in each subclass. For practical purposes, wider reference classes can be used, where we trace over all information which is uncorrelated to the outcome of the experiment, or whose correlation with it is beyond our current understanding. We argue that, once we have gathered all practically available evidence, the optimal strategy for making predictions is to consider ourselves typical in any reference class we belong to, unless we have evidence to the contrary. In the latter case, the class must be correspondingly narrowed.Comment: Minor clarifications adde

The Genetic Component of the Forced Diving Bradycardia Response in Mammals

We contrasted the forced diving bradycardia between two genetically similar (inbred) rat strains (Fischer and Buffalo), compared to that of outbred rats (Wistar). The animals were habituated to forced diving for 4 weeks. Each animal was then tested during one 40 s dive on each of 3 days. The heart rate (fH) was measured before, during, and after each dive. Fischer and Buffalo exhibited marked difference in dive bradycardia (Fischer: 120.9 ± 14.0 beats min−1 vs. Buffalo: 92.8 ± 12.8 beats min−1, P < 0.05). Outbred rats showed an intermediate response (103.0 ± 30.9 beats min−1) but their between-animal variability in mean dive fH and pre-diving resting fH were higher than the inbred strains (P < 0.05), which showed no difference (P > 0.05). The decreased variability in fH in inbred rats as compared with the outbred group indicates that reduced genetic variability minimizes variability of the diving bradycardia between individuals. Heritability within strains was assessed by the repeatability (R) index and was 0.93 ± 0.05 for the outbred, 0.84 ± 0.16 for Buffalo, and 0.80 ± 0.12 for Fischer rats for fH during diving. Our results suggest that a portion of the mammalian diving bradycardia may be a heritable trait

Self-reported and measured weight, height and body mass index (BMI) in Italy, the Netherlands and North America

Background: Self-reported values of height and weight are used increasingly despite warnings that these data - and derived body mass index (BMI) values - might be biased. The present study investigates whether differences between self-reported and measured values are the same for populations from different regions, and the influences of gender and age. Methods: Differences between self-reported and measured weights, heights and resulting BMIs are compared for representative samples of the adult population of Italy, the Netherlands and North America. Results: We observed that weight is under-reported (1.1 ± 2.6 kg for females and 0.4 ± 3.1 kg for males) and height over-reported (1.1 ± 2.2 cm for females and 1.7 ± 2.1 cm for males), in accordance with the literature. This leads to an overall underestimation of BMI values (0.7 ± 1.2 kg/m2 or 2.8 for females and 0.6 ± 1.1 kg/m2 or 2.3 for males). When BMI values are assigned to four categories (from 'underweight' to 'obesity'), 11.2 of the females and 12.0 of the males are categorized too low when self-reported weights and heights are used, with an extreme of 17.2 for Italian females. Older people tend to relatively over-report height and under-report weight, but the magnitude differs between countries and gender. Conclusion: We conclude that, apart from a general overestimation of height and underestimation of weight resulting in an underestimation of BMI, substantial differences are observed between countries, between females and males and between age groups. © The Author 2010. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved

Delayed union of femoral fractures in older rats:decreased gene expression

BACKGROUND: Fracture healing slows with age. While 6-week-old rats regain normal bone biomechanics at 4 weeks after fracture, one-year-old rats require more than 26 weeks. The possible role of altered mRNA gene expression in this delayed union was studied. Closed mid-shaft femoral fractures were induced followed by euthanasia at 0 time (unfractured) or at 1, 2, 4 or 6 weeks after fracture in 6-week-old and 12-15-month-old Sprague-Dawley female rats. mRNA levels were measured for osteocalcin, type I collagen α1, type II collagen, bone morphogenetic protein (BMP)-2, BMP-4 and the type IA BMP receptor. RESULTS: For all of the genes studied, the mRNA levels increased in both age groups to a peak at one to two weeks after fracture. All gene expression levels decreased to very low or undetectable levels at four and six weeks after fracture for both age groups. At four weeks after fracture, the younger rats were healed radiographically, but not the older rats. CONCLUSIONS: (1) All genes studied were up-regulated by fracture in both age groups. Thus, the failure of the older rats to heal promptly was not due to the lack of expression of any of the studied genes. (2) The return of the mRNA gene expression to baseline values in the older rats prior to healing may contribute to their delayed union. (3) No genes were overly up-regulated in the older rats. The slower healing response of the older rats did not stimulate a negative-feedback increase in the mRNA expression of stimulatory cytokines

A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score

Genome-wide association studies have identified a number of single-nucleotide polymorphisms (SNPs) that are associated with psychiatric diseases. Increasing body of evidence suggests a complex connection of SNPs and the transcriptional and epigenetic regulation of gene expression, which is poorly understood. In the current study, we investigated the interplay between genetic risk variants, shifts in methylation and mRNA levels in whole blood from 223 adolescents distinguished by a risk for developing psychiatric disorders. We analyzed 37 SNPs previously associated with psychiatric diseases in relation to genome-wide DNA methylation levels using linear models, with Bonferroni correction and adjusting for cell-type composition. Associations between DNA methylation, mRNA levels and psychiatric disease risk evaluated by the Development and Well-Being Assessment (DAWBA) score were identified by robust linear models, Pearson's correlations and binary regression models. We detected five SNPs (in HCRTR1, GAD1, HADC3 and FKBP5) that were associated with eight CpG sites, validating five of these SNP-CpG pairs. Three of these CpG sites, that is, cg01089319 (GAD1), cg01089249 (GAD1) and cg24137543 (DIAPH1), manifest in significant gene expression changes and overlap with active regulatory regions in chromatin states of brain tissues. Importantly, methylation levels at cg01089319 were associated with the DAWBA score in the discovery group. These results show how distinct SNPs linked with psychiatric diseases are associated with epigenetic shifts with relevance for gene expression. Our findings give a novel insight on how genetic variants may modulate risks for the development of psychiatric diseases

The universe formation by a space reduction cascade with random initial parameters

In this paper we discuss the creation of our universe using the idea of extra dimensions. The initial, multidimensional Lagrangian contains only metric tensor. We have found many sets of the numerical values of the Lagrangian parameters corresponding to the observed low-energy physics of our universe. Different initial parameters can lead to the same values of fundamental constants by the appropriate choice of a dimensional reduction cascade. This result diminishes the significance of the search for the 'unique' initial Lagrangian. We also have obtained a large number of low-energy vacua, which is known as a 'landscape' in the string theory.Comment: 17 pages, 1 figur

Natural History of Meningioma Development in Mice Reveals: A Synergy of Nf2 and p16Ink4a Mutations

Meningiomas account for approximately 30% of all primary central nervous system tumors and are found in half of neurofibromatosis type 2 patients often causing significant morbidity. Although most meningiomas are benign, 10% are classified as atypical or anaplastic, displaying aggressive clinical behavior. Biallelic inactivation of the neurofibromatosis 2 (NF2) tumor suppressor is associated with meningioma formation in all NF2 patients and 60% of sporadic meningiomas. Deletion of the p16INK4a/p14ARF locus is found in both benign and malignant meningiomas, while mutation of the p53 tumor suppressor gene is uncommon. Previously, we inactivated Nf2 in homozygous conditional knockout mice by adenoviral Cre delivery and showed that Nf2 loss in arachnoid cells is rate-limiting for meningioma formation. Here, we report that additional nullizygosity for p16Ink4a increases the frequency of meningioma and meningothelial proliferation in these mice without modifying the tumor grade. In addition, by using magnetic resonance imaging (MRI) to screen a large cohort of mutant mice, we were able to detect meningothelial proliferation and meningioma development opening the way to future studies in which therapeutic interventions can be tested as preclinical assessment of their potential clinical application

The Temporal Singularity: time-accelerated simulated civilizations and their implications

Provided significant future progress in artificial intelligence and computing, it may ultimately be possible to create multiple Artificial General Intelligences (AGIs), and possibly entire societies living within simulated environments. In that case, it should be possible to improve the problem solving capabilities of the system by increasing the speed of the simulation. If a minimal simulation with sufficient capabilities is created, it might manage to increase its own speed by accelerating progress in science and technology, in a way similar to the Technological Singularity. This may ultimately lead to large simulated civilizations unfolding at extreme temporal speedups, achieving what from the outside would look like a Temporal Singularity. Here we discuss the feasibility of the minimal simulation and the potential advantages, dangers, and connection to the Fermi paradox of the Temporal Singularity. The medium-term importance of the topic derives from the amount of computational power required to start the process, which could be available within the next decades, making the Temporal Singularity theoretically possible before the end of the century.Comment: To appear in the conference proceedings of the AGI-18 conference (published in the Springer's Lecture Notes in AI series

Quantum key distribution in terms of the Greenberger-Horne-Zeilinger state: multi-key generation

In this paper, we develop a quantum key distribution protocol based on the Greenberger-Horne-Zeilinger states (GHZs). The particles are exchanged among the users in blocks through two steps. In this protocol, for three-particle GHZs three keys can be simultaneously generated. The advantage of this is that the users can select the most suitable key for communication. The protocol can be generalized to $N$ users to provide $N$ keys. The protocol has two levels for checking the eavesdroppers. Moreover, we discuss the security of the protocol against different attacks.Comment: 10 Page, no figures. Comments are most welcom

HIT: linking herbal active ingredients to targets

The information of protein targets and small molecule has been highly valued by biomedical and pharmaceutical research. Several protein target databases are available online for FDA-approved drugs as well as the promising precursors that have largely facilitated the mechanistic study and subsequent research for drug discovery. However, those related resources regarding to herbal active ingredients, although being unusually valued as a precious resource for new drug development, is rarely found. In this article, a comprehensive and fully curated database for Herb Ingredients’ Targets (HIT, http://lifecenter.sgst.cn/hit/) has been constructed to complement above resources. Those herbal ingredients with protein target information were carefully curated. The molecular target information involves those proteins being directly/indirectly activated/inhibited, protein binders and enzymes whose substrates or products are those compounds. Those up/down regulated genes are also included under the treatment of individual ingredients. In addition, the experimental condition, observed bioactivity and various references are provided as well for user's reference. Derived from more than 3250 literatures, it currently contains 5208 entries about 1301 known protein targets (221 of them are described as direct targets) affected by 586 herbal compounds from more than 1300 reputable Chinese herbs, overlapping with 280 therapeutic targets from Therapeutic Targets Database (TTD), and 445 protein targets from DrugBank corresponding to 1488 drug agents. The database can be queried via keyword search or similarity search. Crosslinks have been made to TTD, DrugBank, KEGG, PDB, Uniprot, Pfam, NCBI, TCM-ID and other databases