Wellesley College

Double-stranded ribonucleic acid (dsRNA) serves as a danger signal associated with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. We report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-alpha and proinflammatory, as well as regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and genetic complementation, we show that murine TLR7 and human TLR8 mediate species-specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a physiological ligand for TLR7 and TLR8.

Abstract Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

Abstract Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 ; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 ; analyses timings and patterns of tumour evolution 7 ; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 ; and evaluates a range of more-specialized features of cancer genomes 8,10–18 .

This article explores the social theory and consequent methodology that underpins studies of transnational migration. First, we propose a social field approach to the study of migration and distinguish between ways of being and ways of belonging in that field. Second, we argue that assimilation and enduring transnational ties are neither incompatible nor binary opposites. Third, we highlight social processes and institutions that are routinely obscured by traditional migration scholarship but that become clear when we use a transnational lens. Finally, we locate our approach to migration research within a larger intellectual project, taken up by scholars of transnational processes in many fields, to rethink and reformulate the concept of society such that it is no longer automatically equated with the boundaries of a single nation-state.

Through work to bring materials from women's studies into the rest of the curriculum, I have often noticed men's unwillingness to grant that they are overprivileged, even though they may grant that women are disadvantaged. They may say they will work to women's statues, in the society, the university, or the curriculum, but they can't or won't support the idea of lessening men's. Denials that amount to taboos surround the subject of advantages that men gain from women's disadvantages. These denials protect male privilege from being fully acknowledged, lessened, or ended.

Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NF kappa B. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.

A review of 45 studies clearly demonstrated that sexually abused children had more symptoms than nonabused children, with abuse accounting for 15-45% of the variance. Fears, posttraumatic stress disorder, behavior problems, sexualized behaviors, and poor self-esteem occurred most frequently among a long list of symptoms noted, but no one symptom characterized a majority of sexually abused children. Some symptoms were specific to certain ages, and approximately one third of victims had no symptoms. Penetration, the duration and frequency of the abuse, force, the relationship of the perpetrator to the child, and maternal support affected the degree of symptomatology. About two thirds of the victimized children showed recovery during the first 12-18 months. The findings suggest the absence of any specific syndrome in children who have been sexually abused and no single traumatizing process.

Abstract The purpose of this paper is to examine the usefulness of factor analysis in developing and evaluating personality scales that measure limited domain constructs The approach advocated follows from several assumptions that a single scale ought to measure a single construct, that factor analysis ought to be applied routinely to new personality scales, and that the factors of a scale are important if it can be demonstrated that they are differentially related to other measures A detailed study of the Self‐Monitoring Scale illustrates how factor analysis can help us to understand what a scale measures A second example uses the self‐esteem literature to illustrate how factor analysis can clarify the proliferation of scales within a single content domain Both examples show how factor analysis can be used to identify important conceptual distinctions Confirmatory techniques are also introduced as a means for testing specific hypotheses It is concluded that factor analysis can make an important contribution to programmatic research in personality psychology

article Free Access Share on End-to-end arguments in system design Authors: J. H. Saltzer M.I.T. Laboratory for Computer Science, 545 Technology Square, Cambridge, MA M.I.T. Laboratory for Computer Science, 545 Technology Square, Cambridge, MAView Profile , D. P. Reed Software Arts, Inc., 27 Mica Lane, Wellesley, MA Software Arts, Inc., 27 Mica Lane, Wellesley, MAView Profile , D. D. Clark M.I.T. Laboratory for Computer Science, 545 Technology Square, Cambridge, MA M.I.T. Laboratory for Computer Science, 545 Technology Square, Cambridge, MAView Profile Authors Info & Claims ACM Transactions on Computer SystemsVolume 2Issue 4Nov. 1984 pp 277–288https://doi.org/10.1145/357401.357402Online:01 November 1984Publication History 1,259citation21,347DownloadsMetricsTotal Citations1,259Total Downloads21,347Last 12 Months1,460Last 6 weeks358 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF

First published in 1957, this essential classic work bridged the gap between analytical and theoretical biology, thus setting the insights of the former in a context which more sensitively reflects the ambiguities surrounding many of its core concepts and objectives. Specifically, these five essays are concerned with some of the major problems of classical biology: the precise character of biological organisation, the processes which generate it, and the specifics of evolution. With regard to these issues, some thinkers suggest that biological organisms are not merely distinguishable from inanimate ‘things’ in terms of complexity, but are in fact radically different qualitatively: they exemplify some constitutive principle which is not elsewhere manifested. It is the desire to bring such ideas into conformity with our understanding of analytical biology which unifies these essays. They explore the contours of a conceptual framework sufficiently wide to embrace all aspects of living systems.

Abstract Transcriptome assays are increasingly being performed by high-throughput RNA sequencing (RNA-seq). For organisms whose genomes have not been sequenced and annotated, transcriptomes must be assembled de novo from the RNA-seq data. Here, we present novel algorithms, specific to bacterial gene structures and transcriptomes, for analysis of bacterial RNA-seq data and de novo transcriptome assembly. The algorithms are implemented in an open source software system called Rockhopper 2. We find that Rockhopper 2 outperforms other de novo transcriptome assemblers and offers accurate and efficient analysis of bacterial RNA-seq data. Rockhopper 2 is available at http://cs.wellesley.edu/~btjaden/Rockhopper .

In many forested ecosystems, the architecture and functional ecology of certain tree species define forest structure and their species-specific traits control ecosystem dynamics. Such foundation tree species are declining throughout the world due to introductions and outbreaks of pests and pathogens, selective removal of individual taxa, and over-harvesting. Through a series of case studies, we show that the loss of foundation tree species changes the local environment on which a variety of other species depend; how this disrupts fundamental ecosystem processes, including rates of decomposition, nutrient fluxes, carbon sequestration, and energy flow; and dramatically alters the dynamics of associated aquatic ecosystems. Forests in which dynamics are controlled by one or a few foundation species appear to be dominated by a small number of strong interactions and may be highly susceptible to alternating between stable states following even small perturbations. The ongoing decline of many foundation species provides a set of important, albeit unfortunate, opportunities to develop the research tools, models, and metrics needed to identify foundation species, anticipate the cascade of immediate, short- and long-term changes in ecosystem structure and function that will follow from their loss, and provide options for remedial conservation and management.

, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.

"Many studies highlight the macro-level dissemination of global culture and institutions. This article focuses on social remittances--a local-level, migration-driven form of cultural diffusion. Social remittances are the ideas, behaviors, identities, and social capital that flow from receiving- to sending-country communities. The role that these resources play in promoting immigrant entrepreneurship, community and family formation, and political integration is widely acknowledged. This article specifies how these same ideas and practices are remolded in receiving countries, the mechanisms by which they are sent back to sending communities, and the role they play in transforming sending-country social and political life." The data concern migrants from the Dominican Republic to the Boston area of the United States.

BACKGROUND: A frequent complication of anticancer treatment, oral and gastrointestinal (GI) mucositis, threatens the effectiveness of therapy because it leads to dose reductions, increases healthcare costs, and impairs patients' quality of life. The Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an international multidisciplinary panel of experts to create clinical practice guidelines for the prevention, evaluation, and treatment of mucositis. METHODS: The panelists examined medical literature published from January 1966 through May 2002, presented their findings at two separate conferences, and then created a writing committee that produced two articles: the current study and another that codifies the clinical implications of the panel's findings in practice guidelines. RESULTS: New evidence supports the view that oral mucositis is a complex process involving all the tissues and cellular elements of the mucosa. Other findings suggest that some aspects of mucositis risk may be determined genetically. GI proapoptotic and antiapoptotic gene levels change along the GI tract, perhaps explaining differences in the frequency with which mucositis occurs at different sites. Studies of mucositis incidence in clinical trials by quality and using meta-analysis techniques produced estimates of incidence that are presented herein for what to our knowledge may be a broader range of cancers than ever presented before. CONCLUSIONS: Understanding the pathobiology of mucositis, its incidence, and scoring are essential for progress in research and care directed at this common side-effect of anticancer therapies.

The psychological study of creativity is essential to human progress. If strides are to be made in the sciences, humanities, and arts, we must arrive at a far more detailed understanding of the creative process, its antecedents, and its inhibitors. This review, encompassing most subspecialties in the study of creativity and focusing on twenty-first-century literature, reveals both a growing interest in creativity among psychologists and a growing fragmentation in the field. To be sure, research into the psychology of creativity has grown theoretically and methodologically sophisticated, and researchers have made important contributions from an ever-expanding variety of disciplines. But this expansion has not come without a price. Investigators in one subfield often seem unaware of advances in another. Deeper understanding requires more interdisciplinary research, based on a systems view of creativity that recognizes a variety of interrelated forces operating at multiple levels.

The Work Preference Inventory (WPI) is designed to assess individual differences in intrinsic and extrinsic motivational orientations. Both the college student and the working adult versions aim to capture the major elements of intrinsic motivation (self-determination, competence, task involvement, curiosity, enjoyment, and interest) and extrinsic motivation (concerns with competition, evaluation, recognition, money or other tangible incentives, and constraint by others). The instrument is scored on two primary scales, each subdivided into 2 secondary scales. The WPI has meaningful factor structures, adequate internal consistency, good short-term test-retest reliability, and good longer term stability. Moreover, WPI scores are related in meaningful ways to other questionnaire and behavioral measures of motivation, as well as personality characteristics, attitudes, and behaviors.

Localization of model category structures: Summary of part 1 Local spaces and localization The localization model category for spaces Localization of model categories Existence of left Bousfield localizations Existence of right Bousfield localizations Fiberwise localization Homotopy theory in model categories: Summary of part 2 Model categories Fibrant and cofibrant approximations Simplicial model categories Ordinals, cardinals, and transfinite composition Cofibrantly generated model categories Cellular model categories Proper model categories The classifying space of a small category The Reedy model category structure Cosimplicial and simplicial resolutions Homotopy function complexes Homotopy limits in simplicial model categories Homotopy limits in general model categories Index Bibliography.

The past two decades have witnessed a sea change in migration scholarship. Most scholars now recognize that many contemporary migrants and their predecessors maintain various kinds of ties to their homelands at the same time that they are incorporated into the countries that receive them. Increasingly, social life takes place across borders, even as the political and cultural salience of nation-state boundaries remains strong. Transnational migration studies has emerged as an inherently interdisciplinary field, made up of scholars around the world, seeking to describe and analyze these dynamics and invent new methodological tools with which to do so. In this review, we offer a short history of theoretical developments, outlining the different ways in which scholars have defined and approached transnational migration. We then summarize what is known about migrant transnationalism in different arenas—economics, politics, the social, the cultural, and the religious. Finally, we discuss methodological implications for the study of international migration, present promising new scholarship, and highlight future research directions.

Researchers studying the role institutions play in causing and confronting environmental change use a variety of concepts and methods that make it difficult to compare their findings. Seeking to remedy this problem, Oran Young takes the analytic themes identified in the Institutional Dimensions of Global Environmental Change (IDGEC) Science Plan as cutting-edge research concerns and develops them into a common structure for conducting research. He illustrates his arguments with examples of environmental change ranging in scale from the depletion of local fish stocks to the disruption of Earth's climate system.Young not only explores theoretical concerns such as the relative merits of collective-action and social-practice models of institutions but also addresses the IDGEC-identified problems of institutional fit, interplay, and scale. He shows how institutions interact both with one another and with the biophysical environment and assesses the extent to which we can apply lessons drawn from the study of local institutions to the study of global institutions and vice versa. He examines how research on institutions can help us to solve global problems of environmental governance. Substantive topics discussed include the institutional dimensions of carbon management, the performance of exclusive economic zones, and the political economy of boreal and tropical forests.