Microcanonical description of (micro) black holes

The microcanonical ensemble is the proper ensemble to describe black holes which are not in thermodynamic equilibrium, such as radiating black holes. This choice of ensemble eliminates the problems, e.g. negative specific heat and loss of unitarity, encountered when the canonical ensemble is used. In this review we present an overview of the weaknesses of the standard thermodynamic description of black holes and show how the microcanonical approach can provide a consistent description of black holes and their Hawking radiation at all energy scales. Our approach is based on viewing the horizon area as yielding the ensemble density at fixed system energy. We then compare the decay rates of black holes in the two different pictures. Our description is particularly relevant for the analysis of micro-black holes whose existence is predicted in models with extra- spatial dimensions.Comment: Review article published in Entropy special issue "Entropy in quantum gravity", editor R. Garattin

Toward an Interoperability and Integration Framework to Enable Digital Thread

This article discusses ongoing research investigating the feasibility of supporting an interoperability and integration framework to enable the digital thread, or an authoritative source of truth with current technology. The question that initiated this exploratory research was, “Is there current technology that can enable cross-domain digital artifact data sharing needed for the digital thread?” A thorough review and investigation of current state-of-the-art model-based systems engineering was performed by reviewing literature and performing multiple site visits and interviews with organizations at the forefront of digital engineering. After this initial investigation and review, a Semantic Web-enabled framework that would allow data in the thread to be captured, stored, transferred, checked for completeness and consistency, and changed under revision change control management began to be formed. This framework has gone through revisions. This paper reflects the most current demonstration of the framework and its capability of acquiring digital data, and parsing and querying the data using Semantic Web technology to generate a decision table that allows the decision data to be visualized. The article concludes with future demonstrations of the framework to further advance toward a framework that can enable a digital thread in practice

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Renormalisation group improved leptogenesis in family symmetry models

We study renormalisation group (RG) corrections relevant for leptogenesis in the case of family symmetry models such as the Altarelli-Feruglio A4 model of tri-bimaximal lepton mixing or its extension to tri-maximal mixing. Such corrections are particularly relevant since in large classes of family symmetry models, to leading order, the CP violating parameters of leptogenesis would be identically zero at the family symmetry breaking scale, due to the form dominance property. We find that RG corrections violate form dominance and enable such models to yield viable leptogenesis at the scale of right-handed neutrino masses. More generally, the results of this paper show that RG corrections to leptogenesis cannot be ignored for any family symmetry model involving sizeable neutrino and tau Yukawa couplings.Comment: 24 pages, 6 figures and 1 tabl

Anti-Angiogenic Therapy Induces Integrin-Linked Kinase 1 Up-Regulation in a Mouse Model of Glioblastoma

BACKGROUND: In order to improve our understanding of the molecular pathways that mediate tumor proliferation and angiogenesis, and to evaluate the biological response to anti-angiogenic therapy, we analyzed the changes in the protein profile of glioblastoma in response to treatment with recombinant human Platelet Factor 4-DLR mutated protein (PF4-DLR), an inhibitor of angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: U87-derived experimental glioblastomas were grown in the brain of xenografted nude mice, treated with PF4-DLR, and processed for proteomic analysis. More than fifty proteins were differentially expressed in response to PF4-DLR treatment. Among them, integrin-linked kinase 1 (ILK1) signaling pathway was first down-regulated but then up-regulated after treatment for prolonged period. The activity of PF4-DLR can be increased by simultaneously treating mice orthotopically implanted with glioblastomas, with ILK1-specific siRNA. As ILK1 is related to malignant progression and a poor prognosis in various types of tumors, we measured ILK1 expression in human glioblastomas, astrocytomas and oligodendrogliomas, and found that it varied widely; however, a high level of ILK1 expression was correlated to a poor prognosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that identifying the molecular pathways induced by anti-angiogenic therapies may help the development of combinatorial treatment strategies that increase the therapeutic efficacy of angiogenesis inhibitors by association with specific agents that disrupt signaling in tumor cells