Large entropy production inside black holes: a simple model

Particles dropped into a rotating black hole can collide near the inner horizon with enormous energies. The entropy produced by these collisions can be several times larger than the increase in the horizon entropy due to the addition of the particles. In this paper entropy is produced by releasing large numbers of neutrons near the outer horizon of a rotating black hole such that they collide near the inner horizon at energies similar to those achieved at the Relativistic Heavy Ion Collider. The increase in horizon entropy is approximately 80 per dropped neutron pair, while the entropy produced in the collisions is 160 per neutron pair. The collision entropy is produced inside the horizon, so this excess entropy production does not violate Bousso's bound limiting the entropy that can go through the black hole's horizon. The generalized laws of black hole thermodynamics are obeyed. No individual observer inside the black hole sees a violation of the second law of thermodynamicsComment: 10 page

The holographic principle

There is strong evidence that the area of any surface limits the information content of adjacent spacetime regions, at 10^(69) bits per square meter. We review the developments that have led to the recognition of this entropy bound, placing special emphasis on the quantum properties of black holes. The construction of light-sheets, which associate relevant spacetime regions to any given surface, is discussed in detail. We explain how the bound is tested and demonstrate its validity in a wide range of examples. A universal relation between geometry and information is thus uncovered. It has yet to be explained. The holographic principle asserts that its origin must lie in the number of fundamental degrees of freedom involved in a unified description of spacetime and matter. It must be manifest in an underlying quantum theory of gravity. We survey some successes and challenges in implementing the holographic principle.Comment: 52 pages, 10 figures, invited review for Rev. Mod. Phys; v2: reference adde

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Correlates of Injury-forced Work Reduction for Massage Therapists and Bodywork Practitioners†

Background: Injury-forced work reduction (IFWR) has been acknowledged as an all-toocommon occurrence for massage therapists and bodywork practitioners (M & Bs). However, little prior research has specifically investigated demographic, work attitude, and perceptual correlates of IFWR among M & Bs. Purpose: To test two hypotheses, H1 and H2. H1 is that the accumulated cost variables set ( e.g., accumulated costs, continuing education costs) will account for a significant amount of IFWR variance beyond control/demographic (e.g., social desirability response bias, gender, years in practice, highest education level) and work attitude/perception variables (e.g., job satisfaction, affective occupation commitment, occupation identification, limited occupation alternatives) sets. H2 is that the two exhaustion variables (i.e., physical exhaustion, work exhaustion) set will account for significant IFWR variance beyond control/demographic, work attitude/perception, and accumulated cost variables sets. Research Design and Participants: An online survey sample of 2,079 complete-data M & Bs was collected. Stepwise regression analysis was used to test the study hypotheses. The research design first controlled for control/demographic (Step1) and work attitude/perception variables sets (Step 2), before then testing for the successive incremental impact of two variable sets, accumulated costs (Step 3) and exhaustion variables (Step 4) for explaining IFWR. Results: Results supported both study hypotheses: accumulated cost variables set (H1) and exhaustion variables set (H2) each significantly explained IFWR after the control/demographic and work attitude/perception variables sets. The most important correlate for explaining IFWR was higher physical exhaustion, but work exhaustion was also significant. It is not just physical “wear and tear”, but also “mental fatigue”, that can lead to IFWR for M & Bs. Being female, having moreyears in practice, and having higher continuing education costs were also significant correlates of IFWR. Conclusions: Lower overall levels of work exhaustion, physical exhaustion, and IFWR were found in the present sample. However, since both types of exhaustion significantly and positively impact IFWR, taking sufficient time between massages and, if possible, varying one’s massage technique to replenish one’s physical and mental energy seem important. Failure to take required continuing education units, due to high costs, also increases risk for IFWR. Study limitations and future research issues are discussed

Using high-density DNA methylation arrays to profile copy number alterations.

The integration of genomic and epigenomic data is an increasingly popular approach for studying the complex mechanisms driving cancer development. We have developed a method for evaluating both methylation and copy number from high-density DNA methylation arrays. Comparing copy number data from Infinium HumanMethylation450 BeadChips and SNP arrays, we demonstrate that Infinium arrays detect copy number alterations with the sensitivity of SNP platforms. These results show that high-density methylation arrays provide a robust and economic platform for detecting copy number and methylation changes in a single experiment. Our method is available in the ChAMP Bioconductor package: http://www.bioconductor.org/packages/2.13/bioc/html/ChAMP.html

A large community outbreak of waterborne giardiasis- delayed detection in a non-endemic urban area

BACKGROUND: Giardia is not endemic in Norway, and more than 90% of reported cases acquire the infection abroad. In late October 2004, an increase in laboratory confirmed cases of giardiasis was reported in the city of Bergen. An investigation was started to determine the source and extent of the outbreak in order to implement control measures. METHODS: Cases were identified through the laboratory conducting giardia diagnostics in the area. All laboratory-confirmed cases were mapped based on address of residence, and attack rates and relative risks were calculated for each water supply zone. A case control study was conducted among people living in the central area of Bergen using age- and sex matched controls randomly selected from the population register. RESULTS: The outbreak investigation showed that the outbreak started in late August and peaked in early October. A total of 1300 laboratory-confirmed cases were reported. Data from the Norwegian Prescription Database gave an estimate of 2500 cases treated for giardiasis probably linked to the outbreak. There was a predominance of women aged 20–29 years, with few children or elderly. The risk of infection for persons receiving water from the water supply serving Bergen city centre was significantly higher than for those receiving water from other supplies. Leaking sewage pipes combined with insufficient water treatment was the likely cause of the outbreak. CONCLUSION: Late detection contributed to the large public health impact of this outbreak. Passive surveillance of laboratory-confirmed cases is not sufficient for timely detection of outbreaks with non-endemic infections

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Diagnostic classification of childhood cancer using multiscale transcriptomics

The causes of pediatric cancers’ distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types