Saving Database Copies to OCI Immutable Buckets

Databases managed by CERN's IT department are crucial for research operations. Although multiple mechanisms for data protection and availability already exist, these databases might still be vulnerable to ransomware attacks. In this report we describe the design and implementation of a tool that copies Oracle Database files to immutable buckets, a feature offered by Oracle's Object Storage cloud service. The buckets' time-based retention rules guarantee that an attacker cannot delete or modify backup files no matter the degree of access gained within CERN's systems

Building effective database backup and recovery monitoring using elastic stack

The data produced at CERN is critical for both physics and administrative purposes. These data must be reachable and available at every moment. To ensure its availability, the CERN IT-DB group implements a full backup and recovery system to protect data against a loss and be able to recover it. In order to monitor the backup and recovery activities and be able to detect eventual errors, a huge number of logs are generated. Those logs must be analyzed to provide us knowledge about the health of the system. In this project, we would like to test the Elastic stack solution to analyze the generated logs so as to monitor the backup and recovery system. In this report, we outline the process we followed to test the Elastic stack solution in the CERN case after defining some theoretical concepts about backup and recovery system and about log analysis

Tropical Cyclone Simulation in A High-Resolution Atmosphere-Ocean Coupled General Circulation Model

A global high-resolution coupled general circulation model (CGCM) consisting of a T319 atmosphere general circulation model and an eddy-permitted ocean general circulation model is examined in terms of the reproducibility of the northern hemisphere tropical cyclone (TC) activity as well as the large-scale environmental conditions. The CGCM successfully simulates the realistic TC structure, TC-induced ocean response, and TC genesis frequency. The global TC genesis frequency simulated by the high-resolution CGCM is much closer to the observed, compared that simulated by the medium-resolution (T106) CGCM. In addition, the high-resolution CGCM partially reproduces the bimodal seasonal cycle of the North Indian Ocean cyclogenesis, while the medium-resolution CGCM fails to simulate it. The high-resolution CGCM also reasonably reproduces the environmental conditions favorable for the TC genesis: warm sea surface temperature, low-level cyclonic circulation, weak vertical wind shear, and high relative humidity in the mid-troposphere. The eastward extension of monsoon-trough is well simulated by the high-resolution CGCM as observed, compared to the medium-resolution CGCM. There are, however, still some discrepancies between the modeled and observed TC activity. We discuss about the following two discrepancies from the view point of the simulated large-scale environmental conditions: the high-resolution CGCM fails to reproduce the bimodal seasonal cycle of the Arabian cyclogenesis during the pre-monsoon period, and the western North Pacific TC genesis locations are confined in the southwestern part of the western North Pacific. It is found that less Arabian cyclogenesis during the pre-monsoon period is due to the weak low-level cyclonic circulation in the Arabian Sea during this period, although the weak vertical wind shear is well simulated as observed. For the western North Pacific, less TC genesis in the southeastern part of the western North Pacific is found to be due to the failure to simulate the eastward extension of the monsoon-trough up to the international dateline. Compared to a medium-resolution CGCM, one of the advantages of the high-resolution CGCM is the reproduction of the intense TC. Surface wind speed exceeding 20~40 ms-1 is successfully simulated by the high-resolution CGCM, while the TC wind speed simulated by the medium-resolution CGCM is less than 20~30 ms-1. The frequency distribution of TC surface wind speed simulated by the high-resolution CGCM is closer to the observed compared to the medium-resolution CGCM.Edited by K. Oouchi and H. Fudeyas

Comparison of the Hemodynamic Performance of Percutaneous and Surgical Bioprostheses for the Treatment of Severe Aortic Stenosis

ObjectivesThis study was undertaken to compare the hemodynamic performance of a percutaneous bioprosthesis to that of surgically implanted (stented and stentless) bioprostheses for the treatment of severe aortic stenosis.MethodsFifty patients who underwent percutaneous aortic valve implantation (PAVI) with the Cribier-Edwards or Edwards SAPIEN bioprosthetic valve (Edwards Lifesciences, Inc., Irvine, California) were matched 1:1 for sex, aortic annulus diameter, left ventricular ejection fraction, body surface area, and body mass index, with 2 groups of 50 patients who underwent surgical aortic valve replacement (SAVR) with a stented valve (Edwards Perimount Magna [SAVR-ST group]), or a stentless valve (Medtronic Freestyle, Medtronic, Minneapolis, Minnesota [SAVR-SL group]). Doppler echocardiographic data were prospectively obtained before the intervention, at discharge, and at 6- to 12-month follow-up.ResultsMean transprosthetic gradient at discharge was lower (p < 0.001) in the PAVI group (10 ± 4 mm Hg) compared with the SAVR-ST (13 ± 5 mm Hg) and SAVR-SL (14 ± 6 mm Hg) groups. Aortic regurgitation (AR) occurred more frequently in the PAVI group (mild: 42%, moderate: 8%) compared with the SAVR-ST (mild: 10%, moderate: 0%) and SAVR-SL (mild: 12%, moderate: 0%) groups (p < 0.0001). At follow-up, the mean gradient in the PAVI group remained lower (p < 0.001) than that of the SAVR-ST group, but was similar to that of the SAVR-SL group. The incidence of severe prosthesis-patient mismatch was significantly lower (p = 0.007) in the PAVI group (6%) compared with the SAVR-ST (28%) and SAVR-SL (20%) groups. However, the incidence of AR remained higher (p < 0.0001) in the PAVI group compared with the 2 other groups.ConclusionsPAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR

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

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies