Biomedical ontologies are emerging as critical tools in genomic and proteomic research where complex data in disparate resources need to be integrated. A number of ontologies exist that describe the properties that can be attributed to proteins; for example, protein functions are described by Gene Ontology, while human diseases are described by Disease Ontology. There is, however, a gap in the current set of ontologies—one that describes the protein entities themselves and their relationships. We have designed a PRotein Ontology (PRO) (...) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modification). PRO will allow the specification of relationships between PRO, GO and other OBO Foundry ontologies. Here we describe the initial development of PRO, illustrated using human proteins from the TGF-beta signaling pathway. (shrink)

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to (...) UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments. (shrink)

The Protein Ontology (PRO; http://purl.obolibrary.org/obo/pr) formally defines and describes taxon-specific and taxon-neutral protein-related entities in three major areas: proteins related by evolution; proteins produced from a given gene; and protein-containing complexes. PRO thus serves as a tool for referencing protein entities at any level of specificity. To enhance this ability, and to facilitate the comparison of such entities described in different resources, we developed a standardized representation of proteoforms using UniProtKB as a sequence reference and PSI-MOD as a post-translational modification (...) reference. We illustrate its use in facilitating an alignment between PRO and Reactome protein entities. We also address issues of scalability, describing our first steps into the use of text mining to identify protein-related entities, the large-scale import of proteoform information from expert curated resources, and our ability to dynamically generate PRO terms. Web views for individual terms are now more informative about closely-related terms, including for example an interactive multiple sequence alignment. Finally, we describe recent improvement in semantic utility, with PRO now represented in OWL and as a SPARQL endpoint. These developments will further support the anticipated growth of PRO and facilitate discoverability of and allow aggregation of data relating to protein entities. (shrink)

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

Research has indicated that microRNAs (miRNAs), a special class of non-coding RNAs (ncRNAs), can perform important roles in different biological and pathological processes. miRNAs’ functions are realized by regulating their respective target genes (targets). It is thus critical to identify and analyze miRNA-target interactions for a better understanding and delineation of miRNAs’ functions. However, conventional knowledge discovery and acquisition methods have many limitations. Fortunately, semantic technologies that are based on domain ontologies can render great assistance in this regard. In our (...) previous investigations, we developed a miRNA domain-specific application ontology, Ontology for MIcroRNA Target (OMIT), to provide the community with common data elements and data exchange standards in the miRNA research. This paper describes (1) our continuing efforts in the OMIT ontology development and (2) the application of the OMIT to enable a semantic approach for knowledge capture of miRNA-target interactions. (shrink)

Identification of non-coding RNAs (ncRNAs) has been significantly enhanced due to the rapid advancement in sequencing technologies. On the other hand, semantic annotation of ncRNA data lag behind their identification, and there is a great need to effectively integrate discovery from relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a precisely defined ncRNA controlled vocabulary, which can fill a specific and highly needed niche in unification of ncRNA biology.

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the (...) domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. (shrink)

In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the (...) domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users. (shrink)

The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of protein (...) research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO provides a framework (...) for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and modified forms. Because (...) proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

Identification of non-coding RNAs (ncRNAs) has been significantly improved over the past decade. On the other hand, semantic annotation of ncRNA data is facing critical challenges due to the lack of a comprehensive ontology to serve as common data elements and data exchange standards in the field. We developed the Non-Coding RNA Ontology (NCRO) to handle this situation. By providing a formally defined ncRNA controlled vocabulary, the NCRO aims to fill a specific and highly needed niche in semantic annotation of (...) large amounts of ncRNA biological and clinical data. (shrink)

Analyses the concept of "energy justice", the notion that energy policy-making should aim to provide all citizens with access to safe, affordable and sustainable energy. Discusses the distributional, procedural and recognition aspects of energy justice, with reference to examples of UK policy-making. Calls for a systems-thinking approach to energy governance.

This paper describes the nexus of energy justice, supply and security. It advances the case that energy justice is the relatively new concept in this triangle of issues and an area requiring research. There are three central tenets of energy justice: distributional, procedural and recognition justice. Each of these tenets figures at certain stages in the energy supply chain and as a consequence there is an effect on energy supply. An example of the wind energy sector in Denmark is presented (...) which demonstrates how the application and promotion of energy justice can enable the growth of an industry supply chain. This in turn contributes to increased energy security and national economic growth. (shrink)

Critiquing any practice, theory, or law, requires understanding the characteristics of the environment which created a need for this law. There are hundreds of different cultures in the world, and each one has its own set of norms, characteristics, and values. What in one country is perceived normal, ethical or unethical, right or wrong, may not be the same somewhere else in the world. The first civilizations begun in Africa and Europe many thousands of years ago when people were hunters (...) and nomads, it is not unreasonable to suspect that many of those traits and characteristics have been socially transferred and/or inherited by future generations. (shrink)

© 2014, Springer International Publishing Switzerland.Purpose: The Patient-Reported Outcomes Measurement Information System initiative was developed to advance the methodology of PROs applicable to chronic diseases. Chronic obstructive pulmonary disease is a progressive chronic disease associated with poor health. This study was designed to examine the correlation of PROMIS health-related quality of life scales and clinical measures among COPD patients. Methods: A cross-sectional analysis was conducted comparing patients who were stable with those currently experiencing a COPD exacerbation. All PROMIS measures for (...) adults available at the time of the study, disease-targeted and other HRQOL instruments, health literacy, percent predicted FEV1, and a 6-min walk distance were assessed when patients were considered clinically stable. Results: Stable COPD patients reported significantly better health-related quality of life on PROMIS domains than patients experiencing an exacerbation. PROMIS domain scores were significantly correlated with each of legacy measures. Six-min walk scores were most highly correlated with the PROMIS physical function domain scores followed by the fatigue, social and to a lesser extent depression, and anxiety domain scores. Percent predicted FEV1 score was significantly associated with PROMIS physical function scores. Conclusion: This study provides support for the validity of the PROMIS measures in COPD patients. (shrink)

The ambition of this conference was to deliver a first examination of how policy is delivered in the context of low-carbon energy infrastructure in the UK. The UK has been developing policy in this area since 2002 (Heffron, 2013). Finally, as the decade passed, in November 2012 an Energy Bill was put before the UK Parliament. One of the chief purposes of this Energy Bill is to establish the right environment for new electricity generation infrastructure in the low-carbon sector. There (...) is significant debate on how this will be achieved and, indeed, whether this piece of legislation will actually deliver this outcome. This conference aimed to examine the dynamics of policy delivery. Throughout the day, there was entertaining discussion as a variety of conference presenters provided interesting contributions on how to deliver such policy goals. In total, there were twelve speakers throughout the day representing the UK (University of Oxford, Pinsent Masons Law Firm, University of Stirling, University of Dundee and University of Aberdeen), and also those who provided lessons from abroad from the University of Copenhagen, Central European University, Milieu Ltd., Pillsbury Law Firm (Washington DC, US) and the Conservation Law Foundation (MA, US). (shrink)

This study aims to highlight how an existential-humanistic perspective can inform athlete support and in doing so, emphasize the importance of explicating the philosophical underpinnings of athlete lifestyle support. Drawing on applied experience with elite youth cricketers over a 12-month period, ethnographic data were collected through the observation, maintenance of case notes, and a practitioner reflective diary. Based on thematic analysis, we created three nonfictional vignettes that we use to illustrate how existential-humanistic theorizing can inform lifestyle support. We discuss the (...) implications of this professional philosophy in terms of considerations for performance and talent development programs, and how holistic support for athletes is positioned. We also discuss implications for athlete lifestyle and performance psychology practitioners, with regard to training, underpinning theoretical grounding of support and the strategic positioning of their practitioner roles. (shrink)

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set has (...) allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Hoping is an integral part of what it is to be human, and its significance for education has been widely noted. Hope is, however, a contested category of human experience and getting to grips with its characteristics and dynamics is a difficult task. The paper argues that hope is not a singular undifferentiated experience and is best understood as a socially mediated human capacity with varying affective, cognitive and behavioural dimensions. Drawing on the philosophy, theology and psychology of hope, five (...) modes of hoping are outlined: patient, critical, sound, resolute and transformative. The key aim of the paper is to illustrate how different modes of hoping are associated with different pedagogical strategies. Phrased differently, the paper seeks to delineate a range of pedagogies of hope. The phrase ‘pedagogy of hope’ is very much associated with critical theory—one thinks instantly of, for example, Paulo Freire, Henry Giroux or bell hooks. There are many pedagogies of hope, however, and an explicitly conservative text such as William Bennett’s Book of Virtues has as strong a claim to the title as Freire’s radical and utopian ideas. A broader argument, therefore, is that there is nothing inherently radical or subversive about a pedagogy of hope. Pedagogies of hope can serve to reproduce social relations as well as to transform them. (shrink)

How do we access the authentic self in order to live fulfilling, meaningful lives? In straightforward terms, The Heart of the Matter: Gifts in Strange Wrapping Paper explains a simple but extraordinarily powerful technique called the See, Feel, Hear Challenge that enables people to easily gain entry into the storehouse of their subconscious core beliefs. In the process, it cracks the coded messages that those beliefs release in the form of disease, suffering, addictions, unhappy relationships, and victimized circumstances. Based in (...) the latest findings in neuroscience and neurocardiology, this book guides readers to an uncomplicated understanding of the astounding power of our emotions and how life automatically delivers experiences that trigger negative reactions that subconsciously impact us. These emotions form the foundation of core beliefs that create unhealthy attitudes and dis-ease patterns that keep us from experiencing the authentic, satisfying lives we desire. Using clear examples and true stories from clients, Dr. Weissman’s latest work demonstrates how we can release these stored emotions and their wisdom via the See, Feel, Hear Challenge. It then explains how to use this simple method to evoke feelings that positively impact the quantum field, remolding our bodies, minds, and everyday lives into purposeful expressions of inner joy and radiant well-being. Whether you’re dealing with addictions, dysfunctional relationships, or illness, or are focused on becoming an Olympic champion, The Heart of the Matter gives you a potent tool for positive change and transformation that you can use for the rest of your life. (shrink)

This study thoroughly investigates the financial behaviors of financially independent, young, single professionals aged 24 to 35 in Balayan, Batangas, amidst a period of global inflation. Focusing on five industries—education, finance, government, healthcare, and retail—the research employs a mixed-methods approach. Quantitative analysis, involving 75 respondents through a 4-point Likert scale survey, is complemented by qualitative insights from in-depth interviews with 5 participants from each industry. The findings from numerical values revealed that demographics did not impact working professionals' saving habits and (...) buying behaviors during the global inflation surge. This suggests that despite differences in age, gender, industry, employment status, and monthly income or salary, all professionals prioritized robust, strong savings and reduced spending to ensure financial stability. The research underscores the significance for professionals in various industries to prioritize specific aspects of personal financial management during the prevailing global inflation surge. The study suggests that, irrespective of industry, working professionals should prioritize specific aspects of personal financial management during the global inflation surge. (shrink)

The recent global economic collapse brings new calls for reform and change as well as a re-examination of the ethical foundations underpining it. Most professors as well as students remain profoundly unhappy with the Business Curricula. The curricula appear to swing between technological training and academic theory. There is little genuine focus on the central issue of the problem: the students’ and faculty’s assumptive world which drives the selection of the materials chosen for presentation as well as the decision-making process. (...) In the pragmatic quest to achieve status within academe, business schools appear to have forgotten that their subject matter is not one cognate domain but a mixture of several areas including mathematics, economics, anthropology, sociology, psychology, logic and planning. Course structures must be redesigned as consilient. That is, each course contains in it the links to other courses and is not expected to be complete in themselves; the new structures proposed are no longer under the direct control of one instructor but each course is under the control of a committee. This creates a linkage between courses that together from a linked chain of knowledge where the strength of the curriculum is tied to the consilient strength of the courses. The result is an organic and developmental model for teaching and learning with a strong ethical foundation as well as developed moral links to effective decision making. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Online education lacks the moral and ethical engagement as well as the empathic interactions that are essential and integral to true liberal education, including business. While the online venue can provide useful information and put libraries at the hands of the student or employee, there is an implicit lack of focus on the sacredness and centrality of the person, his or her values, attitudes, needs, and expectations. The focus of online education is on the delivery of data, not the student’s (...) engagement with the material or the process. Critically absent from online education is the ability to explore the transformation of data as it changes, first to information, then to knowledge, and finally to wisdom, within each person. Finally, absent is the ability to raise the level of abstraction. Since all needs to be measurable in concrete terms in online education, we are left with the language of metrics, such as deliverables, outcomes, inputs, and outputs. Where is the person in all of this? Where is the focus on the moral compass that is so necessary in any type of education? (shrink)

Where one stands to engage with the world is not as some New Age Psychologists continue to argue, completely free and self-determined. Rather, it is formed largely beyond one’s control and is fraught with both dangers and opportunities. This pre-determined point of view is referred to as the Assumptive World (Parkes, 1975). This is defined as a “strongly held set of assumptions about the world and the self that is confidently maintained and used as a means of recognizing, planning and (...) acting…Assumptions such as these are learned and confirmed by the experience of many years” (Parkes, 1975, p. 132). There are, further, levels and intensities of assumptions, as refined by Janoff-Bulman, R. (1992). These assumptions form the centre point of our world and our consciousness. They are so much a part of us that we tend not to challenge them. Though unchallenged, these assumptions nevertheless drive our behaviors, set our expectations, and operationalize our moral views. (shrink)

Contemporary emphasis on creating culturally relevant and context specific knowledge increasingly drives researchers to conduct their work in settings outside their home country. This often requires researchers to build relationships with various stakeholders who may have a vested interest in the research. This case study examines the tension between relationship development with stakeholders and maintaining study integrity, in the context of potential harms, data credibility and cultural sensitivity. We describe an ethical breach in the conduct of global health research by (...) a arising from the ad-hoc participation of a community stakeholder external to the visiting research group. A framework for reflection is developed from a careful examination of underlying factors and presented with a discussion of consequences and mitigation measures. This framework aims to present lessons learned for researchers working abroad who might face similar situations in their work. (shrink)

ABSTRACT Hegel gave the bureaucracy a distinctively corporatist and collegiate structure and insulated it from legislative control. The close match between these features of the Philosophy or Right and the structure of the Prussian bureaucracy, which had been used by reformers to insulate progressive decisions from Junker resistance, suggests that Hegel, too, wanted the bureaucracy to spearhead reform within a hostile environment.