In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.

Long interspersed nuclear elements 1 (LINE-1s) are the only family of mobile genetic elements in the human genome that can move autonomously. They do so by a process called retrotransposition wherein they transcribe to form an mRNA intermediate which is then consequently inserted into the genome by reverse transcription. Despite being silent in normal cells, LINE-1s are highly active in different epithelial tumors. De novo LINE-1 insertions can potentially drive tumorigenesis, and hence it is important to systematically study LINE-1 retrotransposition in cancer. Out of similar to 150 retrotransposition-competent LINE-1s present in the human genome, only a handful of LINE-1 loci, also referred to as "hot" LINE-1s, account for the majority of de novo LINE-1 insertion in different cancer types. We have developed a simple polymerase chain reaction (PCR)-based method to monitor retrotransposition activity of these hot LINE-1s. This method, based on long-distance inverse (LDI)-PCR, takes advantage of 3 ' transduction, a mechanism by which a LINE-1 mobilizes its flanking non-repetitive region, which can subsequently be used to identify de novo LINE-1 3 ' transduction events stemming from a particular hot LINE-1.

In Finland, forensic age assessment is strictly regulated by legislation. According to the Aliens Act (301/2004) and the amendment of the Act (549/2010), the police authorities, the frontier guard authorities, and the immigration authorities have the right to refer asylum seekers to the University of Helsinki, Department of Forensic Medicine, for age assessment. These assessments are especially performed to solve if the person is of major age, the cutoff being 18 completed years. The forensic age assessment is largely based on dental development, since the special permit of the Radiation and Nuclear Safety Authority (STUK) to the Department of Forensic Medicine of the University of Helsinki, allowing the use of ionizing radiation for non-medical purposes, includes dental and hand X-rays. Forensic age assessment is always performed by two forensic odontologists. In 2015, the total number of forensic age assessment examinations was 149, and the countries of origin of the asylum seekers were most commonly Iraq, Afghanistan, and Somalia. The current legislation on forensic age assessment has been well received and approved. Radiological and other examinations can be performed in different parts of Finland, but the forensic odontologist at the University of Helsinki is always involved in the process and ensures joint quality standards for the forensic age assessment.

A measurement of the H -> tau tau signal strength is performed using events recorded in proton-proton collisions by the CMS experiment at the LHC in 2016 at a center-of-mass energy of 13TeV. The data set corresponds to an integrated luminosity of 35.9 fb(-1). The H -> tau tau signal is established with a significance of 4.9 standard deviations, to be compared to an expected significance of 4.7 standard deviations. The best fit of the product of the observed H -> tau tau signal production cross section and branching fraction is 1.09(-0.2)(6+0.27) times the standard model expectation. The combination with the corresponding measurement performed with data collected by the CMS experiment at center-of-mass energies of 7 and 8 TeV leads to an observed significance of 5.9 standard deviations, equal to the expected significance. This is the first observation of Higgs boson decays to tau leptons by a single experiment. (c) 2018 The Author(s). Published by Elsevier B.V.

An inclusive search for anomalous Higgs boson production in the diphoton decay channel and in association with at least one jet is presented, using LHC proton-proton collision data collected by the CMS experiment at a center-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 35.9 fb(-1). The razor variables M-R and R-2, as well as the momentum and mass resolution of the diphoton system, are used to categorize events into different search regions. The search result is interpreted in the context of strong and electroweak production of supersymmetric particles. We exclude bottom squark pair-production with masses below 450 GeV for bottom squarks decaying to a bottom quark, a Higgs boson, and the lightest supersymmetric particle (LSP) for LSP masses below 250 GeV. For wino-like chargino-neutralino production, we exclude charginos with mass below 170 GeV for LSP masses below 25 GeV. In the GMSB scenario, we exclude charginos with mass below 205 GeV for neutralinos decaying to a Higgs boson and a goldstino LSP with 100% branching fraction. C) 2018 The Author(s). Published by Elsevier B.V.

Renal cell carcinoma (RCC) is considered as an immunogenic cancer. Because not all patients respond to current immunotherapies, we aimed to investigate the immunological heterogeneity of RCC tumors. We analyzedthe immunophenotype of the circulating, tumor, and matching adjacent healthy kidney immune cells from 52 nephrectomy patients with multi-parameter flow cytometry. Additionally, we studied the transcriptomic and mutation profiles of 20 clear cell RCC (ccRCC) tumors with bulk RNA sequencing and a customized pan-cancer gene panel. The tumor samples clustered into two distinct subgroups defined by the abundance of intratumoral CD3+ T cells (CD3(high), 25/52) and NK cells (NKhigh, 27/52). CD3(high) tumors had an overall higher frequency of tumor infiltrating lymphocytes and PD-1 expression on the CD8+ T cells compared to NKhigh tumors. The tumor infiltrating T and NK cells had significantly elevated expression levels of LAG-3, PD-1, and HLA-DR compared to the circulating immune cells. Transcriptomic analysis revealed increased immune signaling (IFN-gamma, TNF-alpha via NF-kappa B, and T cell receptor signaling) and kidney metabolism pathways in the CD3(high) subgroup. Genomic analysis confirmed the typical ccRCC mutation profile including VHL, PBRM1, and SETD2 mutations, and revealed PBRM1 as a uniquely mutated gene in the CD3(high) subgroup. Approximately half of the RCC tumors have a high infiltration of NK cells associated with a lower number of tumor infiltrating lymphocytes, lower PD-1 expression, a distinct transcriptomic and mutation profile, providing insights to the immunological heterogeneity of RCC which may impact treatment responses to immunological therapies.

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White-matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach. Moreover, the complex shape of WM pathways and their representation using tractography (streamlines) make the design and evaluation of dissection protocols difficult and time-consuming. The first iteration of Tractostorm quantified the variability of a pyramidal tract dissection protocol and compared results between experts in neuroanatomy and nonexperts. Despite virtual dissection being used for decades, in-depth investigations of how learning or practicing such protocols impact dissection results are nonexistent. To begin to fill the gap, we evaluate an online educational tractography course and investigate the impact learning and practicing a dissection protocol has on interrater (groupwise) reproducibility. To generate the required data to quantify reproducibility across raters and time, 20 independent raters performed dissections of three bundles of interest on five Human Connectome Project subjects, each with four timepoints. Our investigation shows that the dissection protocol in conjunction with an online course achieves a high level of reproducibility (between 0.85 and 0.90 for the voxel-based Dice score) for the three bundles of interest and remains stable over time (repetition of the protocol). Suggesting that once raters are familiar with the software and tasks at hand, their interpretation and execution at the group level do not drastically vary. When compared to previous work that used a different method of communication for the protocol, our results show that incorporating a virtual educational session increased reproducibility. Insights from this work may be used to improve the future design of WM pathway dissection protocols and to further inform neuroanatomical definitions.