Constraints on the near-Earth asteroid obliquity distribution from the Yarkovsky effect

Aims. From lightcurve and radar data we know the spin axis of only 43 near-Earth asteroids. In this paper we attempt to constrain the spin axis obliquity distribution of near-Earth asteroids by leveraging the Yarkovsky effect and its dependence on an asteroid’s obliquity. Methods. By modeling the physical parameters driving the Yarkovsky effect, we solve an inverse problem where we test different simple parametric obliquity distributions. Each distribution results in a predicted Yarkovsky effect distribution that we compare with a X2 test to a dataset of 125 Yarkovsky estimates. Results. We find different obliquity distributions that are statistically satisfactory. In particular, among the considered models, the best-fit solution is a quadratic function, which only depends on two parameters, favors extreme obliquities, consistent with the expected outcomes from the YORP effect, has a 2:1 ratio between retrograde and direct rotators, which is in agreement with theoretical predictions, and is statistically consistent with the distribution of known spin axes of near-Earth asteroids

ORegAnno 3.0: A community-driven resource for curated regulatory annotation

The Open Regulatory Annotation database (ORegAnno) is a resource for curated regulatory annotation. It contains information about regulatory regions, transcription factor binding sites, RNA binding sites, regulatory variants, haplotypes, and other regulatory elements. ORegAnno differentiates itself from other regulatory resources by facilitating crowd-sourced interpretation and annotation of regulatory observations from the literature and highly curated resources. It contains a comprehensive annotation scheme that aims to describe both the elements and outcomes of regulatory events. Moreover, ORegAnno assembles these disparate data sources and annotations into a single, high quality catalogue of curated regulatory information. The current release is an update of the database previously featured in the NAR Database Issue, and now contains 1 948 307 records, across 18 species, with a combined coverage of 334 215 080 bp. Complete records, annotation, and other associated data are available for browsing and download at http://www.oreganno.org/

Negotiating identities: ethnicity and social relations in a young offenders' institution

This article explores the situated nature of male prisoner identities in the late modern British context, using the contrasting theoretical frames of Sykes's (1958) indigenous model and Jacobs' (1979) importation model of prisoner subcultures and social relations. Drawing on eight months of ethnographic fieldwork in an ethnically, religiously and nationally diverse young offenders institution, consideration is given to how prisoners manage and negotiate difference, exploring the contours of racialization and racism which can operate in ambiguous and contradictory ways. Sociological understandings of identity, ethnicity, racialization and racism are used to inform a more empirically grounded theoretical criminology

CIViCpy: A Python software evelopment and analysis toolkit for the CIViC knowledgebase

PURPOSE: Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC Web application. METHODS: To address this limitation, we developed CIViCpy (civicpy.org), a software development kit for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples. RESULTS: We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of \u3e 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors. CONCLUSION: The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online

Fishing for Prion Protein Function

The prion protein is infamous for its role in devastating neurological diseases, but its normal, physiological function has remained mysterious. A new study uses the experimentally tractable zebrafish model to obtain fresh clues to this puzzle

Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer

Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique junctions. To characterize these somatic variants and their associated splice isoforms, we annotate them with the Variant Effect Predictor, SpliceAI, and Genotype-Tissue Expression junction counts and compare our results to other tools that integrate genomic and transcriptomic data. While many events are corroborated by the aforementioned tools, the flexibility of RegTools also allows us to identify splice-associated variants in known cancer drivers, such as TP53, CDKN2A, and B2M, and other genes

Imprisonment and internment: Comparing penal facilities North and South

Recent references to the ‘warehouse prison’ in the United States and the prisión-depósito in Latin America seem to indicate that penal confinement in the western hemisphere has converged on a similar model. However, this article suggests otherwise. It contrasts penal facilities in North America and Latin America in terms of six interrelated aspects: regimentation; surveillance; isolation; supervision; accountability; and formalization. Quantitatively, control in North American penal facilities is assiduous (unceasing, persistent and intrusive), while in Latin America it is perfunctory (sporadic, indifferent and cursory). Qualitatively, North American penal facilities produce imprisonment (which enacts penal intervention through confinement), while in Latin America they produce internment (which enacts penal intervention through release). Closely entwined with this qualitative difference are distinct practices of judicial involvement in sentencing and penal supervision. Those practices, and the cultural and political factors that underpin them, represent an interesting starting point for the explanation of the contrasting nature of imprisonment and internment

Distinct clonal identities of B-ALLs arising after lenolidomide therapy for multiple myeloma

Patients with multiple myeloma (MM) who are treated with lenalidomide rarely develop a secondary B-cell acute lymphoblastic leukemia (B-ALL). The clonal and biological relationship between these sequential malignancies is not yet clear. We identified 17 patients with MM treated with lenalidomide, who subsequently developed B-ALL. Patient samples were evaluated through sequencing, cytogenetics/fluorescence in situ hybridization (FISH), immunohistochemical (IHC) staining, and immunoglobulin heavy chain (IgH) clonality assessment. Samples were assessed for shared mutations and recurrently mutated genes. Through whole exome sequencing and cytogenetics/FISH analysis of 7 paired samples (MM vs matched B-ALL), no mutational overlap between samples was observed. Unique dominant IgH clonotypes between the tumors were observed in 5 paired MM/B-ALL samples. Across all 17 B-ALL samples, 14 (83%) had a TP53 variant detected. Three MM samples with sufficient sequencing depth (\u3e500×) revealed rare cells (average of 0.6% variant allele frequency, or 1.2% of cells) with the same TP53 variant identified in the subsequent B-ALL sample. A lack of mutational overlap between MM and B-ALL samples shows that B-ALL developed as a second malignancy arising from a founding population of cells that likely represented unrelated clonal hematopoiesis caused by a TP53 mutation. The recurrent variants in TP53 in the B-ALL samples suggest a common path for malignant transformation that may be similar to that of TP53-mutant, treatment-related acute myeloid leukemia. The presence of rare cells containing TP53 variants in bone marrow at the initiation of lenalidomide treatment suggests that cellular populations containing TP53 variants expand in the presence of lenalidomide to increase the likelihood of B-ALL development