The arrow of time, black holes, and quantum mixing of large N Yang-Mills theories

Quantum gravity in an AdS spacetime is described by an SU(N) Yang-Mills theory on a sphere, a bounded many-body system. We argue that in the high temperature phase the theory is intrinsically non-perturbative in the large N limit. At any nonzero value of the 't Hooft coupling $\lambda$, an exponentially large (in N^2) number of free theory states of wide energy range (of order N) mix under the interaction. As a result the planar perturbation theory breaks down. We argue that an arrow of time emerges and the dual string configuration should be interpreted as a stringy black hole.Comment: 50 pages 3 figures uses harvma

Identification of novel epigenetic abnormalities as sputum biomarkers for lung cancer risk among smokers and COPD patients

Objectives: Smoking is a common risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Although COPD patients have higher risk of lung cancer compared to non-COPD smokers, the molecular links between these diseases are not well-defined. This study aims to identify genes that are downregulated by cigarette smoke and commonly repressed in COPD and lung cancer. Materials and methods: Primary human airway epithelial cells (HAEC) were exposed to cigarette-smoke-extract (CSE) for 10-weeks and significantly suppressed genes were identified by transcriptome array. Epigenetic abnormalities of these genes in lung adenocarcinoma (LUAD) from patients with or without COPD were determined using genome-wide and gene-specific assays and by in vitro treatment of cell lines with trichostatin-A or 5-aza-2-deoxycytidine. Results: The ten most commonly downregulated genes following chronic CSE exposure of HAEC and show promoter hypermethylation in LUAD were selected. Among these, expression of CCNA1, SNCA, and ZNF549 was significantly reduced in lung tissues from COPD compared with non-COPD cases while expression of CCNA1 and SNCA was further downregulated in tumors with COPD. The promoter regions of all three genes were hypermethylated in LUAD but not normal or COPD lungs. The reduced expression and aberrant promoter hypermethylation of these genes in LUAD were independently validated using data from the Cancer Genome Atlas project. Importantly, SNCA and ZNF549 methylation detected in sputum DNA from LUAD (52% and 38%) cases were more prevalent compared to cancer-free smokers (26% and 15%), respectively (p < 0.02). Conclusions: Our data show that suppression of CCNA1, SNCA, and ZNF549 in lung cancer and COPD occurs with or without promoter hypermethylation, respectively. Detecting methylation of these and previously identified genes in sputum of cancer-free smokers may serve as non-invasive biomarkers for early detection of lung cancer among high risk smokers including COPD patients

Black Holes in Higher-Dimensional Gravity

These lectures review some of the recent progress in uncovering the phase structure of black hole solutions in higher-dimensional vacuum Einstein gravity. The two classes on which we focus are Kaluza-Klein black holes, i.e. static solutions with an event horizon in asymptotically flat spaces with compact directions, and stationary solutions with an event horizon in asymptotically flat space. Highlights include the recently constructed multi-black hole configurations on the cylinder and thin rotating black rings in dimensions higher than five. The phase diagram that is emerging for each of the two classes will be discussed, including an intriguing connection that relates the phase structure of Kaluza-Klein black holes with that of asymptotically flat rotating black holes.Comment: latex, 49 pages, 5 figures. Lectures to appear in the proceedings of the Fourth Aegean Summer School, Mytiline, Lesvos, Greece, September 17-22, 200