Status and Trends of Research in the Field of Project Risk Management

The aim of the article is to determine the contextual and temporal regularities of the development of the presentation in the scientific literature of research in the field of project risk management using bibliometric analysis. To achieve this aim, this study analyzed the following: the trend and structural patterns of publication activity of scholars around the world; the geographical structure of affiliation of scientists; the topics of the most cited articles on project risk management, also a bibliometric analysis using the instrumentarium of VOSviewer v. 1.6.10 as the research tools for analyzing relevant literature from the Scopus database on project risk management. A bibliometric analysis with the central category of «project risk» made it possible to identify eight clusters of scientific research on project risk management: the first cluster is focused on risk management methodology, investment and innovation risk, development and implementation of an innovative product, startup; the second – on project risk management in the field of information technology, information systems, software, identification of risk factors and evaluation of project efficiency; the third – on the optimization of risk management, modeling, the use of methods and instruments in the risk management system (hierarchy analysis method, fuzzy logic method); the fourth – on the assessment of risk probability, cost and complexity of the project; the fifth – on the assessment of the quality of the project, substantiation of the management strategy; the sixth – on the peculiarities of the product life cycle, project infrastructure, management of specific project risks (stakeholders, political situation, technology development); the seventh – on the practical application of standards, algorithms, and models of project risk management; the eighth cluster is based on substantiating the choice of the project, setting risk limits, developing algorithms, and using artificial intelligence. A promising area of management is risk management in the field of information technology, namely: risk management of IT projects and software; development and implementation of startups and innovative products; the use of machine learning and artificial intelligence

PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation and broad H3K27me3 domain formation

Dysregulation of polycomb repressive complex 2 (PRC2) promotes oncogenesis partly through its enzymatic function for inducing trimethylation of histone H3 lysine 27 (H3K27me3). However, it remains to be determined how PRC2 activity is regulated in normal and diseased settings. We here report a PRC2-associated cofactor, PHD finger protein 19 (PHF19; also known as polycomb-like 3), as a crucial mediator of tumorigenicity in multiple myeloma (MM). Overexpression and/or genomic amplification of PHF19 is found associated with malignant progression of MM and plasma cell leukemia, correlating to worse treatment outcomes. Using various MM models, we demonstrated a critical requirement of PHF19 for tumor growth in vitro and in vivo. Mechanistically, PHF19-mediated oncogenic effect relies on its PRC2-interacting and chromatin-binding functions. Chromatin immunoprecipitation followed by sequencing profiling showed a critical role for PHF19 in maintaining the H3K27me3 landscape. PHF19 depletion led to loss of broad H3K27me3 domains, possibly due to impaired H3K27me3 spreading from cytosine guanine dinucleotide islands, which is reminiscent to the reported effect of an “onco”-histone mutation, H3K27 to methionine (H3K27M). RNA-sequencing-based transcriptome profiling in MM lines also demonstrated a requirement of PHF19 for optimal silencing of PRC2 targets, which include cell cycle inhibitors and interferon-JAK-STAT signaling genes critically involved in tumor suppression. Correlation studies using patient sample data sets further support a clinical relevance of the PHF19-regulated pathways. Lastly, we show that MM cells are generally sensitive to PRC2 inhibitors. Collectively, this study demonstrates that PHF19 promotes MM tumorigenesis through enhancing H3K27me3 deposition and PRC2's gene-regulatory functions, lending support for PRC2 blockade as a means for MM therapeutics

Strategies and performance of the CMS silicon tracker alignment during LHC Run 2

The strategies for and the performance of the CMS silicon tracking system alignment during the 2015–2018 data-taking period of the LHC are described. The alignment procedures during and after data taking are explained. Alignment scenarios are also derived for use in the simulation of the detector response. Systematic effects, related to intrinsic symmetries of the alignment task or to external constraints, are discussed and illustrated for different scenarios