label-based security enforcement for web applications

This paper presents SELinks, a programming language focused on building secure multi-tier web applications. SE-Links provides a uniform programming model, in the style of LINQ and Ruby on Rails, with language syntax for accessing objects residing either in the database or at the server. Object-level security policies are expressed as fullycustomizable, first-class labels which may themselves be subject to security policies. Access to labeled data is mediated via trusted, user-provided policy enforcement functions. SELinks has two novel features that ensure security policies are enforced correctly and efficiently. First, SELinks implements a type system called Fable that allows a protected object’s type to refer to its protecting label. The type system can check that labeled data is never accessed directly by the program without first consulting the appropriate policy enforcement function. Second, SELinks compiles policy enforcement code to database-resident user-defined functions that can be called directly during query processing. Database-side checking avoids transferring data to the server needlessly, while still allowing policies to be expressed in a customizable and portable manner. Our experience with two sizable web applications, a model health-care database and a secure wiki with fine-grained security policies, indicates that cross-tier policy enforcement in SELinks is flexible, relatively easy to use, and, when compared to a single-tier approach, improves throughput by nearly an order of magnitude. SELinks is freely available

Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers

Chromosomal translocations are important drivers of hematological malignancies whereby proto-oncogenes are activated by juxtaposition with super-enhancers, often called enhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with super-enhancer hijacking of other common oncogenes in B cell (MAF, MYC and FGFR3/NSD2) and in T-cell malignancies (LMO2, TLX3 and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers

Optical Propagation and Communication

Contains an introduction and reports on four research project.Maryland Procurement Office Contract MDA 904-90-C-5070Charles S. Draper Laboratories Contract DL-H-441698National Institute of Standards and Technology Grant 60-NANBOD-1052U.S. Army Research Office Grant DAAL03-90-G-0128U.S. Navy - Office of Naval Research Grant N00014-89-J-1163U.S. Air Force - Office of Scientific Research Contract F49620-90-C-003

Optical Propagation and Communication

Contains an introduction and reports on five research projects.Maryland Procurement Office Contract MDA 904-90-C-5070National Science Foundation Grant ECS 87-18970National Institute of Standards and Technology Grant 60-NANBOD-1052U.S. Army Research Office Grant DAAL03-90-G-0128U.S. Army Research Office Contract DAAL03-87-K-0117U.S. Navy - Office of Naval Research Grant N00014-89-J-1163U.S. Air Force - Office of Scientific Research Contract F49620-87-C-0043U.S. Air Force - Office of Scientific Research Contract F49620-90-C-003

Optical Propagation and Communication

Contains an introduction and reports on five research projects.Maryland Procurement Office Contract MDA 904-90-C-5070National Science Foundation Grant ECS 87-18970National Institute of Standards and Technology Grant 60-NANBOD-1052U.S. Army Research Office Grant DAAL03-90-G-0128U.S. Army Research Office Contract DAAL03-87-K-0117U.S. Navy - Office of Naval Research Grant N00014-89-J-1163U.S. Air Force - Office of Scientific Research Contract F49620-90-C-003

ETA CARINAE'S THERMAL X-RAY TAIL MEASURED with XMM-Newton and NuSTAR

The evolved, massive highly eccentric binary system, η Car, underwent a periastron passage in the summer of 2014. We obtained two coordinated X-ray observations with XMM-Newton and NuSTAR during the elevated X-ray flux state and just before the X-ray minimum flux state around this passage. These NuSTAR observations clearly detected X-ray emission associated with η Car extending up to ∼50 keV for the first time. The NuSTAR spectrum above 10 keV can be fit with the bremsstrahlung tail from a kT ∼ 6 keV plasma. This temperature is ΔkT ∼ 2 keV higher than those measured from the iron K emission line complex, if the shocked gas is in collisional ionization equilibrium. This result may suggest that the companion star's pre-shock wind velocity is underestimated. The NuSTAR observation near the X-ray minimum state showed a gradual decline in the X-ray emission by 40% at energies above 5 keV in a day, the largest rate of change of the X-ray flux yet observed in individual η Car observations. The column density to the hardest emission component, NH ∼ 1024 H cm-2, marked one of the highest values ever observed for η Car, strongly suggesting increased obscuration of the wind-wind colliding X-ray emission by the thick primary stellar wind prior to superior conjunction. Neither observation detected the power-law component in the extremely hard band that INTEGRAL and Suzaku observed prior to 2011. If the non-detection by NuSTAR is caused by absorption, the power-law source must be small and located very near the wind-wind collision apex. Alternatively, it may be that the power-law source is not related to either η Car or the GeV γ-ray source

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

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

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

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