Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
163
result(s) for
"Cunningham, Fiona"
Sort by:
Dangerous Confidence?
Chinese views of nuclear escalation are key to assessing the potential for nuclear escalation in a crisis or armed conflict between the United States and China, but they have not been examined systematically. A review of original Chinese-language sources and interviews with members of China’s strategic community suggest that China is skeptical that nuclear escalation could be controlled once nuclear weapons are used and, thus, leaders would be restrained from pursuing even limited use. These views are reflected in China’s nuclear operational doctrine (which outlines plans for retaliatory strikes only and lacks any clear plans for limited nuclear use) and its force structure (which lacks tactical nuclear weapons). The long-standing decoupling of Chinese nuclear and conventional strategy, organizational biases within China’s strategic community, and the availability of space, cyber, and conventional missile weapons as alternative sources of strategic leverage best explain Chinese views toward nuclear escalation. China’s confidence that a U.S.-China conflict would not escalate to the use of nuclear weapons may hamper its ability to identify nuclear escalation risks in such a scenario. Meanwhile, U.S. scholars and policymakers emphasize the risk of inadvertent escalation in a conflict with China, but they are more confident than their Chinese counterparts that the use of nuclear weapons could remain limited. When combined, these contrasting views could create pressure for a U.S.-China conflict to escalate rapidly into an unlimited nuclear war.
Journal Article
Assuring Assured Retaliation: China's Nuclear Posture and U.S.-China Strategic Stability
Whether China will abandon its long-standing nuclear strategy of assured retaliation for a first-use posture will be a critical factor in future U.S.-China strategic stability. In the past decade, advances in U.S. strategic capabilities, especially missile defenses and enhanced long-range conventional strike capacity, could undermine China's nuclear retaliatory capability, which is based on a relatively small force and second-strike posture. An exhaustive review of Chinese writings on military affairs indicates, however, that China is unlikely to abandon its current nuclear strategy of assured retaliation. Instead, China will modestly expand its arsenal, increase the sophistication of its forces, and allow limited ambiguity regarding its pledge not to use nuclear weapons first. This limited ambiguity allows China to use the threat of nuclear retaliation to deter a conventional attack on its nuclear arsenal, without significantly increasing the size of its nuclear forces and triggering a costly arms race. Nevertheless, China's effort to maintain its strategy of assured retaliation while avoiding an arms race could backfire. Those efforts increase the risk that nuclear weapons could be used in a crisis between the United States and China, even though China views this possibility as much less likely than the United States does.
Journal Article
A joint NCBI and EMBL-EBI transcript set for clinical genomics and research
Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE
1
and RefSeq
2
launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref.
3
) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.
Matched Annotation from NCBI and EMBL-EBI (MANE) delivers joint transcript sets from Ensembl/GENCODE and RefSeq for standardizing variant reporting in clinical genomics and research.
Journal Article
A standardized framework for representation of ancestry data in genomics studies, with application to the NHGRI-EBI GWAS Catalog
The accurate description of ancestry is essential to interpret, access, and integrate human genomics data, and to ensure that these benefit individuals from all ancestral backgrounds. However, there are no established guidelines for the representation of ancestry information. Here we describe a framework for the accurate and standardized description of sample ancestry, and validate it by application to the NHGRI-EBI GWAS Catalog. We confirm known biases and gaps in diversity, and find that African and Hispanic or Latin American ancestry populations contribute a disproportionately high number of associations. It is our hope that widespread adoption of this framework will lead to improved analysis, interpretation, and integration of human genomics data.
Journal Article
Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP
We aimed to develop an efficient, flexible and scalable approach to diagnostic genome-wide sequence analysis of genetically heterogeneous clinical presentations. Here we present G2P (
www.ebi.ac.uk/gene2phenotype
) as an online system to establish, curate and distribute datasets for diagnostic variant filtering via association of allelic requirement and mutational consequence at a defined locus with phenotypic terms, confidence level and evidence links. An extension to Ensembl Variant Effect Predictor (VEP), VEP-G2P was used to filter both disease-associated and control whole exome sequence (WES) with Developmental Disorders G2P (G2P
DD
; 2044 entries). VEP-G2P
DD
shows a sensitivity/precision of 97.3%/33% for de novo and 81.6%/22.7% for inherited pathogenic genotypes respectively. Many of the missing genotypes are likely false-positive pathogenic assignments. The expected number and discriminative features of background genotypes are defined using control WES. Using only human genetic data VEP-G2P performs well compared to other freely-available diagnostic systems and future phenotypic matching capabilities should further enhance performance.
Diagnostic filtering is an important step to analyze the functional and clinical significance of the large number of genetic variants identified from next-generation genome sequencing data. Here, the authors develop a flexible and scalable system for diagnostic filtering of genetic variants using G2P with Ensembl VEP.
Journal Article
Acrylamide concentration determines the direction and magnitude of helical membrane protein gel shifts
SDS/PAGE is universally used in biochemistry, cell biology, and immunology to resolve minute protein amounts readily from tissue and cell extracts. Although molecular weights of water-soluble proteins are reliably determined from their SDS/PAGE mobility, most helical membrane proteins, which comprise 20–30% of the human genome and the majority of drug targets, migrate to positions that have for decades been unpredictably slower or faster than their actual formula weight, often confounding their identification. Using de novo designed transmembrane-mimetic polypeptides that match the composition of helical membrane-spanning sequences, we quantitate anomalous SDS/PAGE fractionation of helical membrane proteins by comparing the relative mobilities of these polypeptides with typical water-soluble reference proteins on Laemmli gels. We find that both the net charge and effective molecular size of the migrating particles of transmembrane-mimetic species exceed those of the corresponding reference proteins and that gel acrylamide concentration dictates the impact of these two factors on the direction and magnitude of anomalous migration. Algorithms we derived from these data compensate for this differential effect of acrylamide concentration on the SDS/PAGE mobility of a variety of natural membrane proteins. Our results provide a unique means to predict anomalous migration of membrane proteins, thereby facilitating straightforward determination of their molecular weights via SDS/PAGE.
Journal Article
Scaling up data curation using deep learning: An application to literature triage in genomic variation resources
Manually curating biomedical knowledge from publications is necessary to build a knowledge based service that provides highly precise and organized information to users. The process of retrieving relevant publications for curation, which is also known as document triage, is usually carried out by querying and reading articles in PubMed. However, this query-based method often obtains unsatisfactory precision and recall on the retrieved results, and it is difficult to manually generate optimal queries. To address this, we propose a machine-learning assisted triage method. We collect previously curated publications from two databases UniProtKB/Swiss-Prot and the NHGRI-EBI GWAS Catalog, and used them as a gold-standard dataset for training deep learning models based on convolutional neural networks. We then use the trained models to classify and rank new publications for curation. For evaluation, we apply our method to the real-world manual curation process of UniProtKB/Swiss-Prot and the GWAS Catalog. We demonstrate that our machine-assisted triage method outperforms the current query-based triage methods, improves efficiency, and enriches curated content. Our method achieves a precision 1.81 and 2.99 times higher than that obtained by the current query-based triage methods of UniProtKB/Swiss-Prot and the GWAS Catalog, respectively, without compromising recall. In fact, our method retrieves many additional relevant publications that the query-based method of UniProtKB/Swiss-Prot could not find. As these results show, our machine learning-based method can make the triage process more efficient and is being implemented in production so that human curators can focus on more challenging tasks to improve the quality of knowledge bases.
Journal Article
Ensembl variation resources
Background
The maturing field of genomics is rapidly increasing the number of sequenced genomes and producing more information from those previously sequenced. Much of this additional information is variation data derived from sampling multiple individuals of a given species with the goal of discovering new variants and characterising the population frequencies of the variants that are already known. These data have immense value for many studies, including those designed to understand evolution and connect genotype to phenotype. Maximising the utility of the data requires that it be stored in an accessible manner that facilitates the integration of variation data with other genome resources such as gene annotation and comparative genomics.
Description
The Ensembl project provides comprehensive and integrated variation resources for a wide variety of chordate genomes. This paper provides a detailed description of the sources of data and the methods for creating the Ensembl variation databases. It also explores the utility of the information by explaining the range of query options available, from using interactive web displays, to online data mining tools and connecting directly to the data servers programmatically. It gives a good overview of the variation resources and future plans for expanding the variation data within Ensembl.
Conclusions
Variation data is an important key to understanding the functional and phenotypic differences between individuals. The development of new sequencing and genotyping technologies is greatly increasing the amount of variation data known for almost all genomes. The Ensembl variation resources are integrated into the Ensembl genome browser and provide a comprehensive way to access this data in the context of a widely used genome bioinformatics system. All Ensembl data is freely available at
http://www.ensembl.org
and from the public MySQL database server at ensembldb.ensembl.org.
Journal Article
Female Incarceration Rates and Violence Against Women Predict Estimated Prevalence of Modern Slavery
Globally, female incarceration rates are rising faster than those of men. Prisons are highly masculinized environments and often disregard female inmates’ gendered physical and mental healthcare needs. Gendered deficiencies can result in higher recidivism and mortality rates and increased psychological and physical illness for women. Widespread intersecting factors such as structural failures and personal and collective identities have played a role in women’s susceptibility to violence, oppression, and incarceration. We propose that incarceration can be a form of gender-based oppression and violence against women (VAW) and that incarceration serves as a risk multiplier for existing vulnerabilities, including modern slavery victimization. The present study expands on existing literature that explores the complex relationship between VAW, gender inequality, and gendered susceptibility to modern slavery by including an investigation of female incarceration rates. Results indicate that VAW and female incarceration rates significantly predict the estimated prevalence of modern slavery. Further, female homicide, interpersonal violence, and lifetime prevalence of VAW were strong single predictors of modern slavery but not female incarceration. While differences regarding the gendered vulnerabilities to incarceration for women exist across countries, evidence has suggested—and our findings support—that VAW can increase susceptibility to incarceration status for women.
Journal Article