Showing papers by "Yale University published in 2007"
Ewan Birney, John A. Stamatoyannopoulos1, Anindya Dutta2, Roderic Guigó3 +317 more•Institutions (44)
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
5,091 citations
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TL;DR: In this paper, the concept of power is defined in terms of a relation between people, and is expressed in simple symbolic notation, and a statement of power comparability is developed, or the relative degree of power held by two or more persons.
Abstract: What is “power”? Most people have an intuitive notion of what it means. But scientists have not yet formulated a statement of the concept of power that is rigorous enough to be of use in the systematic study of this important social phenomenon. Power is here defined in terms of a relation between people, and is expressed in simple symbolic notation. From this definition is developed a statement of power comparability, or the relative degree of power held by two or more persons. With these concepts it is possible for example, to rank members of the United States Senate according to their “power” over legislation on foreign policy and on tax and fiscal policy.
3,601 citations
TL;DR: In this paper, the transmon was proposed to operate in a regime of significantly increased ratio of Josephson energy and charging energy, while maintaining sufficient anharmonicity for selective qubit control.
Abstract: Short dephasing times pose one of the main challenges in realizing a quantum computer. Different approaches have been devised to cure this problem for superconducting qubits, a prime example being the operation of such devices at optimal working points, so-called ``sweet spots.'' This latter approach led to significant improvement of ${T}_{2}$ times in Cooper pair box qubits [D. Vion et al., Science 296, 886 (2002)]. Here, we introduce a new type of superconducting qubit called the ``transmon.'' Unlike the charge qubit, the transmon is designed to operate in a regime of significantly increased ratio of Josephson energy and charging energy ${E}_{J}∕{E}_{C}$. The transmon benefits from the fact that its charge dispersion decreases exponentially with ${E}_{J}∕{E}_{C}$, while its loss in anharmonicity is described by a weak power law. As a result, we predict a drastic reduction in sensitivity to charge noise relative to the Cooper pair box and an increase in the qubit-photon coupling, while maintaining sufficient anharmonicity for selective qubit control. Our detailed analysis of the full system shows that this gain is not compromised by increased noise in other known channels.
2,807 citations
TL;DR: Qualitative inquiry can improve the description and explanation of complex, real-world phenomena pertinent to health services research as they use these methods themselves or collaborate with qualitative researchers from a wide range of disciplines.
Abstract: Qualitative research is increasingly common in health services research (Shortell 1999; Sofaer 1999). Qualitative studies have been used, for example, to study culture change (Marshall et al. 2003; Craigie and Hobbs 2004), physician–patient relationships and primary care (Flocke, Miller, and Crabtree 2002; Gallagher et al. 2003; Sobo, Seid, and Reyes Gelhard 2006), diffusion of innovations and quality improvement strategies (Bradley et al. 2005; Crosson et al. 2005), novel interventions to improve care (Koops and Lindley 2002; Stapleton, Kirkham, and Thomas 2002; Dy et al. 2005), and managed care market trends (Scanlon et al. 2001; Devers et al. 2003). Despite substantial methodological papers and seminal texts (Glaser and Strauss 1967; Miles and Huberman 1994; Mays and Pope 1995; Strauss and Corbin 1998; Crabtree and Miller 1999; Devers 1999; Patton 1999; Devers and Frankel 2000; Giacomini and Cook 2000; Morse and Richards 2002) about designing qualitative projects and collecting qualitative data, less attention has been paid to the data analysis aspects of qualitative research. The purpose of this paper is to offer practical strategies for the analysis of qualitative data that may be generated from in-depth interviewing, focus groups, field observations, primary or secondary qualitative data (e.g., diaries, meeting minutes, annual reports), or a combination of these data collection approaches.
2,777 citations
TL;DR: It is proposed that translation regulation by microRNPs oscillates between repression and activation during the cell cycle, and two well-studied microRNAs—Let-7 and the synthetic microRNA miRcxcr4—likewise induce translation up-regulation of target mRNAs on cell cycle arrest.
Abstract: AU-rich elements (AREs) and microRNA target sites are conserved sequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha (TNFalpha) mRNA is transformed into a translation activation signal, recruiting Argonaute (AGO) and fragile X mental retardation-related protein 1 (FXR1), factors associated with micro-ribonucleoproteins (microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well-studied microRNAs-Let-7 and the synthetic microRNA miRcxcr4-likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.
2,715 citations
TL;DR: The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections, and recent progress brings us closer to an integrated view of the immune system and its function in host defence.
Abstract: The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
2,656 citations
TL;DR: The results indicate that lipid extraction or normalization is most important when lipid content is variable among consumers of interest or between consumers and end members, and when differences in δ13C between end members is <10–12‰.
Abstract: Within an organism, lipids are depleted in (13)C relative to proteins and carbohydrates (more negative delta(13)C), and variation in lipid content among organisms or among tissue types has the potential to introduce considerable bias into stable isotope analyses that use delta(13)C. Despite the potential for introduced error, there is no consensus on the need to account for lipids in stable isotope analyses. Here we address two questions: (1) If and when is it important to account for the effects of variation in lipid content on delta(13)C? (2) If it is important, which method(s) are reliable and robust for dealing with lipid variation? We evaluated the reliability of direct chemical extraction, which physically removes lipids from samples, and mathematical normalization, which uses the carbon-to-nitrogen (C:N) ratio of a sample to normalize delta(13)C after analysis by measuring the lipid content, the C:N ratio, and the effect of lipid content on delta(13)C (Deltadelta(13)C) of plants and animals with a wide range of lipid contents. For animals, we found strong relationships between C:N and lipid content, between lipid content and Deltadelta(13)C, and between C:N and Deltadelta(13)C. For plants, C:N was not a good predictor of lipid content or Deltadelta(13)C, but we found a strong relationship between carbon content and lipid content, lipid content and Deltadelta(13)C, and between and carbon content and Deltadelta(13)C. Our results indicate that lipid extraction or normalization is most important when lipid content is variable among consumers of interest or between consumers and end members, and when differences in delta(13)C between end members is <10-12 per thousand. The vast majority of studies using natural variation in delta(13)C fall within these criteria. Both direct lipid extraction and mathematical normalization reduce biases in delta(13)C, but mathematical normalization simplifies sample preparation and better preserves the integrity of samples for delta(15)N analysis.
2,103 citations
TL;DR: Thirteen categories of breast tumor markers were considered, six of which were new for the guideline, and certain multiparameter gene expression assays not all applications for these markers were supported, however.
Abstract: Purpose To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer. Methods For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee’s literature review focused attention on available systematic reviews and metaanalyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Recommendations and Conclusions
2,079 citations
TL;DR: The autoantigens of a new category of treatment‐responsive paraneoplastic encephalitis are reported, and it is proposed that this category should be combined with existing treatment-responsive encephalopathy categories.
Abstract: Objective
To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis.
2,079 citations
TL;DR: These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution.
Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
2,057 citations
TL;DR: This chapter presents central requirements for demonstrating mediators and mechanisms of change and reviews current data-analytic and designs approaches and why they fall short of meeting these requirements.
Abstract: There has been enormous progress in psychotherapy research. This has culminated in recognition of several treatments that have strong evidence in their behalf. Even so, after decades of psychotherapy research, we cannot provide an evidence-based explanation for how or why even our most well studied interventions produce change, that is, the mechanism(s) through which treatments operate. This chapter presents central requirements for demonstrating mediators and mechanisms of change and reviews current data-analytic and designs approaches and why they fall short of meeting these requirements. The role of the therapeutic alliance in psychotherapy and cognitive changes in cognitive therapy for depression are highlighted to illustrate key issues. Promising lines of work to identify mediators and mechanisms, ways of bringing to bear multiple types of evidence, recommendations to make progress in understanding how therapy works, and conceptual and research challenges in evaluating mediators and mechanisms are also presented.
National Institutes of Health1, Imperial College London2, Aarhus University3, University of Oxford4, University of Wisconsin-Madison5, University of Toronto6, University of California, Los Angeles7, Columbia University8, National Institute of Radiological Sciences9, University of Michigan10, University of Copenhagen11, University of Turku12, VU University Amsterdam13, Brookhaven National Laboratory14, Pfizer15, Washington University in St. Louis16, Indiana University – Purdue University Indianapolis17, University of Pittsburgh18, University of British Columbia19, Emory University20, Johns Hopkins University21, Yale University22
TL;DR: An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
Abstract: An international group of experts in pharmacokinetic modeling recommends a consensus nomenclature to describe in vivo molecular imaging of reversibly binding radioligands.
TL;DR: It is demonstrated that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium, and these findings suggest thatAutophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.
Abstract: We present a genome-wide association study of ileal Crohn disease and two independent replication studies that identify several new regions of association to Crohn disease. Specifically, in addition to the previously established CARD15 and IL23R associations, we identified strong and significantly replicated associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a coding variant in ATG16L1, the latter of which was also recently reported by another group. We also report strong associations with independent replication to variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on 16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal epithelial cell lines and that functional knockdown of this gene abrogates autophagy of Salmonella typhimurium. Together, these findings suggest that autophagy and host cell responses to intracellular microbes are involved in the pathogenesis of Crohn disease.
TL;DR: The authors make use of transaction-level U.S. trade data to introduce a number of new stylized facts about firms and trade, such as the extensive margins of trade, that is, the number of products firms trade and the countries with which they trade, to understand the role of distance in dampening aggregate trade flows.
Abstract: Despite the fact that importing and exporting are extremely rare firm activities, economists generally devote little attention to the role of firms when discussing international trade. This paper summarizes key differences between trading and non-trading firms, demonstrates how these differences present a challenge to standard trade models and shows how recent "heterogeneous-firm" models of international trade address these challenges. We then make use of transaction-level U.S. trade data to introduce a number of new stylized facts about firms and trade. These facts reveal that the extensive margins of trade -- that is, the number of products firms trade as well as the number of countries with which they trade -- are central to understanding the well-known role of distance in dampening aggregate trade flows.
TL;DR: Clear associations of soft drink intake with increased energy intake and body weight are found and recommended to reduce population soft drink consumption.
Abstract: In a meta-analysis of 88 studies, we examined the association between soft drink consumption and nutrition and health outcomes. We found clear associations of soft drink intake with increased energy intake and body weight. Soft drink intake also was associated with lower intakes of milk, calcium, and other nutrients and with an increased risk of several medical problems (e.g., diabetes).Study design significantly influenced results: larger effect sizes were observed in studies with stronger methods (longitudinal and experimental vs cross-sectional studies). Several other factors also moderated effect sizes (e.g., gender, age, beverage type). Finally, studies funded by the food industry reported significantly smaller effects than did non–industry-funded studies. Recommendations to reduce population soft drink consumption are strongly supported by the available science.
TL;DR: The metabolic syndrome in children and adolescents – an IDF consensus report.
Abstract: Zimmet P, Alberti K George MM, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S; IDF Consensus Group. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatric Diabetes 2007: 8: 299–306. Paul Zimmet, K George MM Alberti, Francine Kaufman, Naoko Tajima, Martin Silink, Silva Arslanian, Gary Wong, Peter Bennett, Jonathan Shaw and Sonia Caprio; IDF Consensus Group International Diabetes Institute, Melbourne, Victoria, Australia; Department of Endocrinology and Metabolic Medicine, St Mary’s Hospital, London, UK; Center for Diabetes, Endocrinology and Metabolism, Children’s Hospital, Los Angeles, CA, USA; Division of Diabetes, Metabolism and Endocrinology, Jikei University School of Medicine, Tokyo, Japan; Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead, Sydney, New South Wales, Australia; Division of Endocrinology, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA; Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong; Phoenix Epidemiology and Clinical Research Branch, NIDDK, National Institutes of Health, Phoenix, AZ, USA; and Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA
TL;DR: This paper found that exporters are larger, more productive, more skill-and capital-intensive, and to pay higher wages than non-exporting firms, and that the top 10 percent of exporters accounted for 96 percent of total U.S. exports.
Abstract: In discussing the origins and implications of international trade, economists usually emphasize comparative advantage, increasing returns to scale, and consumer love of variety, but pay relatively little attention to the firms that actually drive trade flows. Yet engaging in international trade is an exceedingly rare activity: of the 5.5 million firms operating in the United States in 2000, just 4 percent were exporters. Among these exporting firms, the top 10 percent accounted for 96 percent of total U.S. exports. Since the mid-1990s, a large number of empirical studies have provided a wealth of information about the important role thatfirms play in mediating countries’ imports and exports. This research, based on micro datasets that track countries’ production and trade at the firm level, demonstrates that trading firms differ substantially from firms that solely serve the domestic market. Across a wide range of countries and industries, exporters have been shown to be larger, more productive, more skill- and capital-intensive, and to pay higher wages than nonexportingfirms. Furthermore, these
TL;DR: The data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis.
Abstract: Plasmacytoid dendritic cells (pDCs) sense viral and microbial DNA through endosomal Toll-like receptors to produce type 1 interferons. pDCs do not normally respond to self-DNA, but this restriction seems to break down in human autoimmune disease by an as yet poorly understood mechanism. Here we identify the antimicrobial peptide LL37 (also known as CAMP) as the key factor that mediates pDC activation in psoriasis, a common autoimmune disease of the skin. LL37 converts inert self-DNA into a potent trigger of interferon production by binding the DNA to form aggregated and condensed structures that are delivered to and retained within early endocytic compartments in pDCs to trigger Toll-like receptor 9. Thus, our data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis.
TL;DR: A mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and regulates their memory cell potential is elucidated.
TL;DR: This Review describes the functions performed by endothelial cells at each stage of the inflammatory process, emphasizing the principal mediators and signalling pathways involved and the therapeutic implications.
Abstract: Inflammation is usually analysed from the perspective of tissue-infiltrating leukocytes. Microvascular endothelial cells at a site of inflammation are both active participants in and regulators of inflammatory processes. The properties of endothelial cells change during the transition from acute to chronic inflammation and during the transition from innate to adaptive immunity. Mediators that act on endothelial cells also act on leukocytes and vice versa. Consequently, many anti-inflammatory therapies influence the behaviour of endothelial cells and vascular therapeutics influence inflammation. This Review describes the functions performed by endothelial cells at each stage of the inflammatory process, emphasizing the principal mediators and signalling pathways involved and the therapeutic implications.
TL;DR: Two experiments tested how belonging uncertainty undermines the motivation and achievement of people whose group is negatively characterized in academic settings, and an intervention that mitigated doubts about social belonging in college raised the academic achievement of Black students but not of White students.
Abstract: Stigmatization can give rise to belonging uncertainty. In this state, people are sensitive to information diagnostic of the quality of their social connections. Two experiments tested how belonging uncertainty undermines the motivation and achievement of people whose group is negatively characterized in academic settings. In Experiment 1, students were led to believe that they might have few friends in an intellectual domain. Whereas White students were unaffected, Black students (stigmatized in academics) displayed a drop in their sense of belonging and potential. In Experiment 2, an intervention that mitigated doubts about social belonging in college raised the academic achievement (e.g., college grades) of Black students but not of White students. Implications for theories of achievement motivation and intervention are discussed.
TL;DR: The full therapeutic potential of allogeneic haematopoietic SCT will not be realized until approaches to minimize GVHD, while maintaining the positive contributions of donor T cells are developed.
Abstract: Allogeneic haematopoietic stem-cell transplantation (SCT) is a curative therapy for haematological malignancies and inherited disorders of blood cells, such as sickle-cell anaemia. Mature alphabeta T cells that are contained in the allografts reconstitute T-cell immunity and can eradicate malignant cells in the recipient. Unfortunately, these T cells recognize the recipient as 'non-self' and employ a wide range of immune mechanisms to attack recipient tissues in a process known as graft-versus-host disease (GVHD). The full therapeutic potential of allogeneic haematopoietic SCT will not be realized until approaches to minimize GVHD, while maintaining the positive contributions of donor T cells, are developed. This Review focuses on research in mouse models pursued to achieve this goal.
TL;DR: Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis Guadalupe Garcia-Tsao, M.D., co-authors.
TL;DR: In this article, the authors show that if a localized phase at nonzero temperature $Tg0$ exists for strongly disordered and weakly interacting electrons, as recently argued, it will also occur when both disorder and interactions are strong and $T$ is very high.
Abstract: We suggest that if a localized phase at nonzero temperature $Tg0$ exists for strongly disordered and weakly interacting electrons, as recently argued, it will also occur when both disorder and interactions are strong and $T$ is very high. We show that in this high-$T$ regime, the localization transition may be studied numerically through exact diagonalization of small systems. We obtain spectra for one-dimensional lattice models of interacting spinless fermions in a random potential. As expected, the spectral statistics of finite-size samples cross over from those of orthogonal random matrices in the diffusive regime at weak random potential to Poisson statistics in the localized regime at strong randomness. However, these data show deviations from simple one-parameter finite-size scaling: the apparent mobility edge ``drifts'' as the system's size is increased. Based on spectral statistics alone, we have thus been unable to make a strong numerical case for the presence of a many-body localized phase at nonzero $T$.
TL;DR: ChIP-seq identified 41,582 and 11,004 putative STAT1-binding regions in stimulated and unstimulated cells, respectively, and found 24 loci known to contain STAT1 interferon-responsive binding sites, including 24 that were enriched in sequences similar to known STAT1 binding motifs.
Abstract: We developed a method, ChIP-sequencing (ChIP-seq), combining chromatin immunoprecipitation (ChIP) and massively parallel sequencing to identify mammalian DNA sequences bound by transcription factors in vivo. We used ChIP-seq to map STAT1 targets in interferon-γ (IFN-γ)–stimulated and unstimulated human HeLa S3 cells, and compared the method's performance to ChIP-PCR and to ChIP-chip for four chromosomes. By ChIP-seq, using 15.1 and 12.9 million uniquely mapped sequence reads, and an estimated false discovery rate of less than 0.001, we identified 41,582 and 11,004 putative STAT1-binding regions in stimulated and unstimulated cells, respectively. Of the 34 loci known to contain STAT1 interferon-responsive binding sites, ChIP-seq found 24 (71%). ChIP-seq targets were enriched in sequences similar to known STAT1 binding motifs. Comparisons with two ChIP-PCR data sets suggested that ChIP-seq sensitivity was between 70% and 92% and specificity was at least 95%.
Michigan State University1, University of California, Davis2, University of California, Santa Barbara3, Grinnell College4, Florida Institute of Technology5, University of California, San Diego6, Smithsonian Institution7, Cornell University8, Academy of Natural Sciences of Drexel University9, Dartmouth College10, Yale University11, University of Chicago12, University of Missouri13, University of Georgia14, University of British Columbia15
TL;DR: Two major hypotheses for the origin of the latitudinal diversity gradient are reviewed, including the time and area hypothesis and the diversification rate hypothesis, which hold that tropical regions diversify faster due to higher rates of speciation, or due to lower extinction rates.
Abstract: A latitudinal gradient in biodiversity has existed since before the time of the dinosaurs, yet how and why this gradient arose remains unresolved. Here we review two major hypotheses for the origin of the latitudinal diversity gradient. The time and area hypothesis holds that tropical climates are older and historically larger, allowing more opportunity for diversification. This hypothesis is supported by observations that temperate taxa are often younger than, and nested within, tropical taxa, and that diversity is positively correlated with the age and area of geographical regions. The diversification rate hypothesis holds that tropical regions diversify faster due to higher rates of speciation (caused by increased opportunities for the evolution of reproductive isolation, or faster molecular evolution, or the increased importance of biotic interactions), or due to lower extinction rates. There is phylogenetic evidence for higher rates of diversification in tropical clades, and palaeontological data demonstrate higher rates of origination for tropical taxa, but mixed evidence for latitudinal differences in extinction rates. Studies of latitudinal variation in incipient speciation also suggest faster speciation in the tropics. Distinguishing the roles of history, speciation and extinction in the origin of the latitudinal gradient represents a major challenge to future research.
TL;DR: Findings indicate the existence of 2 distinct (but correlated) aspects within each of the Big Five, representing an intermediate level of personality structure between facets and domains.
Abstract: Factor analyses of 75 facet scales from 2 major Big Five inventories, in the Eugene-Springfield community sample (N=481), produced a 2-factor solution for the 15 facets in each domain. These findings indicate the existence of 2 distinct (but correlated) aspects within each of the Big Five, representing an intermediate level of personality structure between facets and domains. The authors characterized these factors in detail at the item level by correlating factor scores with the International Personality Item Pool (L. R. Goldberg, 1999). These correlations allowed the construction of a 100-item measure of the 10 factors (the Big Five Aspect Scales [BFAS]), which was validated in a 2nd sample (N=480). Finally, the authors examined the correlations of the 10 factors with scores derived from 10 genetic factors that a previous study identified underlying the shared variance among the Revised NEO Personality Inventory facets (K. L. Jang et al., 2002). The correspondence was strong enough to suggest that the 10 aspects of the Big Five may have distinct biological substrates.
TL;DR: This work reports an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrates the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response.
Abstract: Semiconducting nanowires have the potential to act as highly sensitive sensors for the detection of pathogenic microorganisms, without the need for a label on the pathogen. Practical miniature sensors would have applications in diagnostics, homeland security and basic research. Current technologies have not been widely adopted for various reasons, including the difficulty of integrating nanoscale devices into practical sensors. Now a team spanning five departments at Yale has developed a new approach to the problem. In a state-of-the-art (CMOS-compatible) system they create miniature, ultra-sensitive sensors that can detect specific unlabelled antibodies at concentrations below 100 femtomolar and are able to monitor the cellular immune response in 'real-time'. A new approach that uses complementary metal oxide semiconductor field effect transistor compatible technology is reported, and demonstrates the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. Semiconducting nanowires have the potential to function as highly sensitive and selective sensors for the label-free detection of low concentrations of pathogenic microorganisms1,2,3,4,5,6,7,8,9,10. Successful solution-phase nanowire sensing has been demonstrated for ions3, small molecules4, proteins5,6, DNA7 and viruses8; however, ‘bottom-up’ nanowires (or similarly configured carbon nanotubes11) used for these demonstrations require hybrid fabrication schemes12,13, which result in severe integration issues that have hindered widespread application. Alternative ‘top-down’ fabrication methods of nanowire-like devices9,10,14,15,16,17 produce disappointing performance because of process-induced material and device degradation. Here we report an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrate the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. This approach eliminates the need for hybrid methods and enables system-scale integration of these sensors with signal processing and information systems. Additionally, the ability to monitor antibody binding and sense the cellular immune response in real time with readily available technology should facilitate widespread diagnostic applications.
National Institutes of Health1, University of Michigan2, University of Texas Health Science Center at Houston3, Harvard University4, Broad Institute5, Fred Hutchinson Cancer Research Center6, University of Oxford7, University of California, Los Angeles8, Yale University9, deCODE genetics10, University of Western Australia11, Washington University in St. Louis12, Howard University13, University of Washington14
TL;DR: What constitutes replication of a genotype–phenotype association, and how best can it be achieved, is investigated.
Abstract: What constitutes replication of a genotype–phenotype association, and how best can it be achieved?
McMaster University1, University of Toronto2, Dalhousie University3, Pennsylvania State University4, Nationwide Children's Hospital5, University of Iowa6, University of Miami7, University of South Carolina8, University of Paris9, Pasteur Institute10, University of Gothenburg11, Icahn School of Medicine at Mount Sinai12, Stanford University13, Vanderbilt University14, Johns Hopkins University15, University of North Carolina at Chapel Hill16, University of California, Los Angeles17, University of Pennsylvania18, Washington University in St. Louis19, University of Chicago20, Harvard University21, Emory University22, George Washington University23, Yale University24, University of Utah25, University of Washington26, University of Pittsburgh27, University of California, Irvine28, Veterans Health Administration29, University of Rochester30, University of Toulouse31, German Cancer Research Center32, Goethe University Frankfurt33, National and Kapodistrian University of Athens34, University of Bologna35, Utrecht University36, Guy's Hospital37, King's College London38, University of Cambridge39, University of Manchester40, Newcastle University41, University of Oxford42, University of Illinois at Chicago43, University of Michigan44, Centre Hospitalier Universitaire de Toulouse45, McGill University46, Autism Speaks47
TL;DR: Linkage and copy number variation analyses implicate chromosome 11p12–p13 and neurexins, respectively, among other candidate loci, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
Abstract: Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.