diffloop: a computational framework for identifying and analyzing differential DNA loops from sequencing data

Abstract Summary The 3D architecture of DNA within the nucleus is a key determinant of interactions between genes, regulatory elements, and transcriptional machinery. As a result, differences in DNA looping structure are associated with variation in gene expression and cell state. To systematically assess changes in DNA looping architecture between samples, we introduce diffloop, an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops. We demonstrate this functionality by detecting differences between ENCODE ChIA-PET samples and relate looping to variability in epigenetic state. Availability and implementation Diffloop is implemented as an R/Bioconductor package available at https://bioconductor.org/packages/release/bioc/html/diffloop.html Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online

Eddy Current Imaging of Aircraft Using Real Time Image Signal Processing

The increased incidence of aircraft component failures as motivated a reassessment of the NDE methods applied to assure fleet airworthiness. In the past, eddy current testing has been limited by the presence of spurious signals, operator error and the lack of permanent test results. An eddy current system using portable precision scanners and signal analysis techniques developed in the nuclear industry has been applied to aircraft inspections. Using custom designed probes, multifrequency mixing, and digital signal processing, the detection criteria of 10% loss of wall on the interior faying surface and cracks 60 mils (1.5 mm) in length have been accomplished. The subtle nature of these flaw conditions and the presence of interfering signals prompted the need for signal processing techniques. To achieve this objective, real time signal processing that requires a minimum of computation has been implemented in an eddy current C-scan imaging system. The signal processing produces spatial displays of amplitude (in phase or quadrature), magnitude, phase of spatial derivatives of these parameters. Permanent images that are more easily interpretable for flaw detection are thus produced

Accurate design of translational output by a neural network model of ribosome distribution

Synonymous codon choice can have dramatic effects on ribosome speed and protein expression. Ribosome profiling experiments have underscored that ribosomes do not move uniformly along mRNAs. Here, we have modeled this variation in translation elongation by using a feed-forward neural network to predict the ribosome density at each codon as a function of its sequence neighborhood. Our approach revealed sequence features affecting translation elongation and characterized large technical biases in ribosome profiling. We applied our model to design synonymous variants of a fluorescent protein spanning the range of translation speeds predicted with our model. Levels of the fluorescent protein in budding yeast closely tracked the predicted translation speeds across their full range. We therefore demonstrate that our model captures information determining translation dynamics in vivo; that this information can be harnessed to design coding sequences; and that control of translation elongation alone is sufficient to produce large quantitative differences in protein output

In situ microphysics observations of intense pyroconvection from a large wildfire

This study characterizes the size and shape distributions of 10 µm to 6 mm diameter particles observed during six penetrations of wildfire-induced pyroconvection near Boise, Idaho, USA, by a research aircraft over the period 29–30 August 2016. In situ measurements by the aircraft include winds, atmospheric state, and bulk water content and particle concentration, size, and shape. These observations are complemented by data from airborne and ground-based radars. One of the penetrations is through a subsaturated smoke–ash plume with negligible cloud liquid water content that is characterized by an updraft of almost 36 m s−1. The size distribution of number concentration is very similar to that documented previously for a smoke plume from a prescribed fire, and particle shapes exhibit qualitative and quantitative attributes comparable to ash particles created in a burn chamber. Particles sampled during this penetration are most likely pyrometeors composed of ash. Pyrocumulus clouds are probed in the other penetrations where values of relative humidity and cloud liquid water content are larger, but updrafts are weaker. Compared to the smoke-plume penetration, size distributions are mostly characterized by larger concentration, and particle shapes exhibit a higher degree of circular symmetry. Particle composition in these pyrocumulus penetrations is most likely a combination of hydrometeors (ice particles) and pyrometeors (ash).</p

Transcript-indexed ATAC-seq for precision immune profiling.

T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples. In peripheral blood CD4+ T cells from healthy individuals, we identified cis and trans regulators of naive and memory T cell states and found substantial heterogeneity in surface-marker-defined T cell populations. In patients with a leukemic form of&nbsp;cutaneous T cell lymphoma, T-ATAC-seq enabled identification of leukemic and nonleukemic regulatory pathways in T cells from the same individual by allowing separation of the signals that arose from the malignant clone from the background T cell noise. Thus, T-ATAC-seq is a new tool that enables analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity and immunotherapy

Childcare, choice and social class: Caring for young children in the UK

This paper draws on the results of two qualitative research projects examining parental engagements with the childcare market in the UK. Both projects are located in the same two London localities. One project focuses on professional middle class parents, and the other on working class families, and we discuss the key importance of social class in shaping parents' differential engagement with the childcare market, and their understandings of the role childcare plays in their children's lives. We identify and discuss the different "circuits" of care (Ball et al 1995) available to and used by families living physically close to each other, but in social class terms living in different worlds. We also consider parents' relationships with carers, and their social networks. We conclude that in order to fully understand childcare policies and practices and families' experiences of care, an analysis which encompasses social class and the workings of the childcare market is needed

Raising children with high self-esteem (but not narcissism)

With the rise of individualism since the 1960s, Western parents have become increasingly concerned with raising children’s self-esteem. This is understandable, given the benefits of self-esteem for children’s psychological health. However, parents’ well-intentioned attempts to raise self-esteem, such as inflated praise, may inadvertently breed narcissism. How, then, can parents raise self-esteem without breeding narcissism? Here, we propose a tripartite model of self-regard, which holds that the development of self-esteem without narcissism can be cultivated through realistic feedback (rather than inflated praise), focus on growth (rather than on outperforming others), and unconditional regard (rather than regard that is conditional). We review evidence in support of these practices and outline promising research directions. The tripartite model integrates existing research, stimulates theory development, and identifies leverage points for intervention concurrently to raise self-esteem and curtail narcissism from a young age