Revisiting the European sovereign bonds with a permutation-information-theory approach

NASA Astrophysics Data System (ADS)

Fernández Bariviera, Aurelio; Zunino, Luciano; Guercio, María Belén; Martinez, Lisana B.; Rosso, Osvaldo A.

2013-12-01

In this paper we study the evolution of the informational efficiency in its weak form for seventeen European sovereign bonds time series. We aim to assess the impact of two specific economic situations in the hypothetical random behavior of these time series: the establishment of a common currency and a wide and deep financial crisis. In order to evaluate the informational efficiency we use permutation quantifiers derived from information theory. Specifically, time series are ranked according to two metrics that measure the intrinsic structure of their correlations: permutation entropy and permutation statistical complexity. These measures provide the rectangular coordinates of the complexity-entropy causality plane; the planar location of the time series in this representation space reveals the degree of informational efficiency. According to our results, the currency union contributed to homogenize the stochastic characteristics of the time series and produced synchronization in the random behavior of them. Additionally, the 2008 financial crisis uncovered differences within the apparently homogeneous European sovereign markets and revealed country-specific characteristics that were partially hidden during the monetary union heyday.

Predictive role of brain connectivity for resective surgery in Lennox-Gastaut syndrome.

PubMed

Hur, Yun Jung; Kim, Heung Dong

2016-08-01

Callosotomy can reveal hidden primary epileptogenic areas in Lennox-Gastaut syndrome (LGS). We studied the significance of causal connectivity for identifying hidden epileptogenic areas in preoperative electroencephalography (EEG) and for making a decision regarding resective surgery. We enrolled 18 LGS patients who underwent corpus callosotomy. Eight patients with unilateral epileptogenicity on post-callosotomy EEG underwent resective surgery (group A). Ten patients with independent bilateral epileptogenicity did not undergo resective surgery (group B). We analyzed generalized epileptiform discharges on pre-callosotomy EEG via direct directed transfer function (dDTF) and partial directed coherence (PDC). All regions exhibiting unilaterality in group A and bilaterality identified by dDTF or PDC in group B were concordant with the lateralization of the irritative zone on post-callosotomy EEG and with the localization of the resective areas, except for one patient in group A. The regions identified by dDTF exhibited high concordance rates with the resective areas in patients with good outcomes. Causal connectivity methods showed good concordance with hidden epileptogenic areas, and its concordance was associated with the prognosis of surgical outcome. This study provides evidence that causal connectivity methods can be helpful in deciding which type of surgery will be suitable for an LGS patient. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Discovering Hidden Connections among Diseases, Genes and Drugs Based on Microarray Expression Profiles with Negative-Term Filtering

PubMed Central

2014-01-01

Microarrays based on gene expression profiles (GEPs) can be tailored specifically for a variety of topics to provide a precise and efficient means with which to discover hidden information. This study proposes a novel means of employing existing GEPs to reveal hidden relationships among diseases, genes, and drugs within a rich biomedical database, PubMed. Unlike the co-occurrence method, which considers only the appearance of keywords, the proposed method also takes into account negative relationships and non-relationships among keywords, the importance of which has been demonstrated in previous studies. Three scenarios were conducted to verify the efficacy of the proposed method. In Scenario 1, disease and drug GEPs (disease: lymphoma cancer, lymph node cancer, and drug: cyclophosphamide) were used to obtain lists of disease- and drug-related genes. Fifteen hidden connections were identified between the diseases and the drug. In Scenario 2, we adopted different diseases and drug GEPs (disease: AML-ALL dataset and drug: Gefitinib) to obtain lists of important diseases and drug-related genes. In this case, ten hidden connections were identified. In Scenario 3, we obtained a list of disease-related genes from the disease-related GEP (liver cancer) and the drug (Capecitabine) on the PharmGKB website, resulting in twenty-two hidden connections. Experimental results demonstrate the efficacy of the proposed method in uncovering hidden connections among diseases, genes, and drugs. Following implementation of the weight function in the proposed method, a large number of the documents obtained in each of the scenarios were judged to be related: 834 of 4028 documents, 789 of 1216 documents, and 1928 of 3791 documents in Scenarios 1, 2, and 3, respectively. The negative-term filtering scheme also uncovered a large number of negative relationships as well as non-relationships among these connections: 97 of 834, 38 of 789, and 202 of 1928 in Scenarios 1, 2, and 3, respectively. PMID:24915461

Hidden long evolutionary memory in a model biochemical network

NASA Astrophysics Data System (ADS)

Ali, Md. Zulfikar; Wingreen, Ned S.; Mukhopadhyay, Ranjan

2018-04-01

We introduce a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. Starting with a functional core module, random evolutionary drift increases network complexity even in the absence of specific selective pressures. Surprisingly, we uncover a hidden order in sequence space that gives rise to long-term evolutionary memory, implying strong constraints on network evolution due to the topology of accessible sequence space.

DNA barcodes, species delimitation, and bioassessment: issues of diversity, analysis, and standardization

EPA Science Inventory

DNA barcoding has the capability to uncover cryptic diversity otherwise undetectable using morphology alone. For aquatic bioassessment, this opportunity to discover hidden biodiversity presents new data for incorporation into environmental monitoring programs. Unfortunately, the ...

Uncovering the "Hidden Dimension": Proxemic Research Techniques Applied to Teacher Preparation.

ERIC Educational Resources Information Center

Levis-Pilz, Gladys

1982-01-01

Classroom observation assignments for preservice teachers allow them to observe detailed relationships among classroom space and teacher student interaction. Through structured observation, preservice teachers become aware of classroom interactions in a vivid and instructive manner. (CJ)

Category transfer in sequential causal learning: the unbroken mechanism hypothesis.

PubMed

Hagmayer, York; Meder, Björn; von Sydow, Momme; Waldmann, Michael R

2011-07-01

The goal of the present set of studies is to explore the boundary conditions of category transfer in causal learning. Previous research has shown that people are capable of inducing categories based on causal learning input, and they often transfer these categories to new causal learning tasks. However, occasionally learners abandon the learned categories and induce new ones. Whereas previously it has been argued that transfer is only observed with essentialist categories in which the hidden properties are causally relevant for the target effect in the transfer relation, we here propose an alternative explanation, the unbroken mechanism hypothesis. This hypothesis claims that categories are transferred from a previously learned causal relation to a new causal relation when learners assume a causal mechanism linking the two relations that is continuous and unbroken. The findings of two causal learning experiments support the unbroken mechanism hypothesis. Copyright © 2011 Cognitive Science Society, Inc.

Unveiling causal activity of complex networks

NASA Astrophysics Data System (ADS)

Williams-García, Rashid V.; Beggs, John M.; Ortiz, Gerardo

2017-07-01

We introduce a novel tool for analyzing complex network dynamics, allowing for cascades of causally-related events, which we call causal webs (c-webs), to be separated from other non-causally-related events. This tool shows that traditionally-conceived avalanches may contain mixtures of spatially-distinct but temporally-overlapping cascades of events, and dynamical disorder or noise. In contrast, c-webs separate these components, unveiling previously hidden features of the network and dynamics. We apply our method to mouse cortical data with resulting statistics which demonstrate for the first time that neuronal avalanches are not merely composed of causally-related events. The original version of this article was uploaded to the arXiv on March 17th, 2016 [1].

Healing the Split Between the Gospel and the Media Culture.

ERIC Educational Resources Information Center

McDonnell, Jim

1998-01-01

Implores educators to help people discern between real and false paths to God as advertised in contemporary culture and mass media, and to communicate the Christian message in ways that uncover the transcendent meaning hidden in popular culture. (VWC)

Retrieving hydrological connectivity from empirical causality in karst systems

NASA Astrophysics Data System (ADS)

Delforge, Damien; Vanclooster, Marnik; Van Camp, Michel; Poulain, Amaël; Watlet, Arnaud; Hallet, Vincent; Kaufmann, Olivier; Francis, Olivier

2017-04-01

Because of their complexity, karst systems exhibit nonlinear dynamics. Moreover, if one attempts to model a karst, the hidden behavior complicates the choice of the most suitable model. Therefore, both intense investigation methods and nonlinear data analysis are needed to reveal the underlying hydrological connectivity as a prior for a consistent physically based modelling approach. Convergent Cross Mapping (CCM), a recent method, promises to identify causal relationships between time series belonging to the same dynamical systems. The method is based on phase space reconstruction and is suitable for nonlinear dynamics. As an empirical causation detection method, it could be used to highlight the hidden complexity of a karst system by revealing its inner hydrological and dynamical connectivity. Hence, if one can link causal relationships to physical processes, the method should show great potential to support physically based model structure selection. We present the results of numerical experiments using karst model blocks combined in different structures to generate time series from actual rainfall series. CCM is applied between the time series to investigate if the empirical causation detection is consistent with the hydrological connectivity suggested by the karst model.

Analysis of complex neural circuits with nonlinear multidimensional hidden state models

PubMed Central

Friedman, Alexander; Slocum, Joshua F.; Tyulmankov, Danil; Gibb, Leif G.; Altshuler, Alex; Ruangwises, Suthee; Shi, Qinru; Toro Arana, Sebastian E.; Beck, Dirk W.; Sholes, Jacquelyn E. C.; Graybiel, Ann M.

2016-01-01

A universal need in understanding complex networks is the identification of individual information channels and their mutual interactions under different conditions. In neuroscience, our premier example, networks made up of billions of nodes dynamically interact to bring about thought and action. Granger causality is a powerful tool for identifying linear interactions, but handling nonlinear interactions remains an unmet challenge. We present a nonlinear multidimensional hidden state (NMHS) approach that achieves interaction strength analysis and decoding of networks with nonlinear interactions by including latent state variables for each node in the network. We compare NMHS to Granger causality in analyzing neural circuit recordings and simulations, improvised music, and sociodemographic data. We conclude that NMHS significantly extends the scope of analyses of multidimensional, nonlinear networks, notably in coping with the complexity of the brain. PMID:27222584

What is the nature of causality in the brain? - Inherently probabilistic. Comment on "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

NASA Astrophysics Data System (ADS)

Dhamala, Mukesh

2015-12-01

Understanding cause-and-effect (causal) relations from observations concerns all sciences including neuroscience. Appropriately defining causality and its nature, though, has been a topic of active discussion for philosophers and scientists for centuries. Although brain research, particularly functional neuroimaging research, is now moving rapidly beyond identification of brain regional activations towards uncovering causal relations between regions, the nature of causality has not be been thoroughly described and resolved. In the current review article [1], Mannino and Bressler take us on a beautiful journey into the history of the work on causality and make a well-reasoned argument that the causality in the brain is inherently probabilistic. This notion is consistent with brain anatomy and functions, and is also inclusive of deterministic cases of inputs leading to outputs in the brain.

The Hidden Curriculum: What Are We Actually Teaching about the Fundamentals of Care?

PubMed

MacMillan, Kathleen

2016-01-01

The issues of missed or inadequately provided basic nursing care and related complications are being identified as worldwide phenomena of interest. Without being aware of it, educators and practicing nurses may be teaching nursing students that fundamental nursing care is unimportant, uncomplicated and not really nursing's responsibility. This paper explores the concept of the "hidden curriculum" in nursing education, as it relates to fundamental nursing care and calls for greater partnerships between education and service to uncover the hidden curriculum; to effectively shape it to achieve alignment between classroom and practice; and, ultimately, to improve care processes and patient outcomes through collaboration. A renewed focus on the vital importance of what is considered "basics" to patient outcomes is required in nursing education. Copyright © 2016 Longwoods Publishing.

Uncovering the "Hidden" Multilingualism of Europe: An Italian Case Study

ERIC Educational Resources Information Center

Tamburelli, Marco

2014-01-01

Dominant notions of what constitutes a "language" and what a "dialect" within a continuum are entirely based on sociopolitical factors (i.e. the "languages by 'Ausbau'" of Kloss), totally disregarding structural and communicative aspects. This paper argues that such stance is no longer tenable in view of the modern…

Sitting on a Gold Mine.

ERIC Educational Resources Information Center

Zanic, Tom; Kirchenstein, Joel

1998-01-01

Many districts are holding property that could be put to better use. With a creative strategy for planning, analyzing, and implementing a plan for these public properties, local boards and administrators can uncover hidden value in their real estate assets. California's Santa Monica-Malibu Unified School District now receives $500,000 a year in…

Making the Case for Demographic Data in Extension Programming

ERIC Educational Resources Information Center

Curtis, Katherine J.; Verdoff, Daniel; Rizzo, Bill; Beaudoin, James

2012-01-01

Understanding one's community is essential for effective Extension programming across all program areas. The use of current and reliable demographic data is crucial for Extension to develop effective education and programming to track change and to uncover hidden community characteristics. We discuss what demographic data are, present…

Uncovering the hidden: complexity and strategies for diagnosing latent tuberculosis.

PubMed

Flores-Valdez, Mario Alberto

2017-10-24

Tuberculosis produces two clinical manifestations: active and latent (non-apparent) disease. The latter is estimated to affect one-third of the world population and constitutes a source of continued transmission should the disease emerge from its hidden state (reactivation). Methods to diagnose latent TB have been evolving and aim to detect the disease in people who are truly infected with M. tuberculosis , versus those where other mycobacteria, or even other pathologies not related to TB, are present. The current use of proteomic and transcriptomic approaches may lead to improved detection methods in the coming years.

Anisotropic scene geometry resampling with occlusion filling for 3DTV applications

NASA Astrophysics Data System (ADS)

Kim, Jangheon; Sikora, Thomas

2006-02-01

Image and video-based rendering technologies are receiving growing attention due to their photo-realistic rendering capability in free-viewpoint. However, two major limitations are ghosting and blurring due to their sampling-based mechanism. The scene geometry which supports to select accurate sampling positions is proposed using global method (i.e. approximate depth plane) and local method (i.e. disparity estimation). This paper focuses on the local method since it can yield more accurate rendering quality without large number of cameras. The local scene geometry has two difficulties which are the geometrical density and the uncovered area including hidden information. They are the serious drawback to reconstruct an arbitrary viewpoint without aliasing artifacts. To solve the problems, we propose anisotropic diffusive resampling method based on tensor theory. Isotropic low-pass filtering accomplishes anti-aliasing in scene geometry and anisotropic diffusion prevents filtering from blurring the visual structures. Apertures in coarse samples are estimated following diffusion on the pre-filtered space, the nonlinear weighting of gradient directions suppresses the amount of diffusion. Aliasing artifacts from low density are efficiently removed by isotropic filtering and the edge blurring can be solved by the anisotropic method at one process. Due to difference size of sampling gap, the resampling condition is defined considering causality between filter-scale and edge. Using partial differential equation (PDE) employing Gaussian scale-space, we iteratively achieve the coarse-to-fine resampling. In a large scale, apertures and uncovered holes can be overcoming because only strong and meaningful boundaries are selected on the resolution. The coarse-level resampling with a large scale is iteratively refined to get detail scene structure. Simulation results show the marked improvements of rendering quality.

Great apes (Pan paniscus, Pan troglodytes, Gorilla gorilla, Pongo abelii) follow visual trails to locate hidden food.

PubMed

Völter, Christoph J; Call, Josep

2014-05-01

Whether nonhuman primates understand causal relations beyond mere associations is still a matter of debate. We presented all four species of nonhuman great apes (N = 36) with a choice between 2 opaque, upside down cups after displacing them out of sight from their starting positions. Crucially, 1 of them had left a yogurt trail behind it. Great apes spontaneously used the trail to select the yogurt baited cup. Follow-up experiments demonstrated that chimpanzees distinguished trails based on the temporal order of cause and effect by ignoring trails that were already present before the reward was hidden. Additionally, chimpanzees did not select cups based on the amount of yogurt near them but instead preferred cups that signaled the endpoint of the trail. We conclude that apes' choices reveal sensitivity to a causal relation between cause (reward) and effect (trail) including their temporal order. ©2014 APA, all rights reserved.

Quantum Steering Beyond Instrumental Causal Networks

NASA Astrophysics Data System (ADS)

Nery, R. V.; Taddei, M. M.; Chaves, R.; Aolita, L.

2018-04-01

We theoretically predict, and experimentally verify with entangled photons, that outcome communication is not enough for hidden-state models to reproduce quantum steering. Hidden-state models with outcome communication correspond, in turn, to the well-known instrumental processes of causal inference but in the one-sided device-independent scenario of one black-box measurement device and one well-characterized quantum apparatus. We introduce one-sided device-independent instrumental inequalities to test against these models, with the appealing feature of detecting entanglement even when communication of the black box's measurement outcome is allowed. We find that, remarkably, these inequalities can also be violated solely with steering, i.e., without outcome communication. In fact, an efficiently computable formal quantifier—the robustness of noninstrumentality—naturally arises, and we prove that steering alone is enough to maximize it. Our findings imply that quantum theory admits a stronger form of steering than known until now, with fundamental as well as practical potential implications.

Uncovering the Hidden Meaning of Cross-Curriculum Comparison Results on the Force Concept Inventory

ERIC Educational Resources Information Center

Ding, Lin; Caballero, Marcos D.

2014-01-01

In a recent study, Caballero and colleagues conducted a large-scale evaluation using the Force Concept Inventory (FCI) to compare student learning outcomes between two introductory physics curricula: the Matter and Interactions (M&I) mechanics course and a pedagogically-reformed-traditional-content (PRTC) mechanics course. Using a conventional…

Context, Complexity and Contestation: Birmingham's Agreed Syllabuses for Religious Education since the 1970s

ERIC Educational Resources Information Center

Parker, Stephen G.; Freathy, Rob J. K.

2011-01-01

The present article offers an historical perspective on the 1975, 1995 and 2007 Birmingham Agreed Syllabuses for Religious Education. It draws upon historical evidence uncovered as part of "The hidden history of curriculum change in religious education in English schools, 1969-1979" project, and curriculum history theories, especially…

How to Show One-Fourth? Uncovering Hidden Context through Reciprocal Learning

ERIC Educational Resources Information Center

Abramovich, S.; Brouwer, P.

2007-01-01

This paper suggests that mathematics teacher educators should listen carefully to what their students are saying. More specifically, it demonstrates how from one pre-teacher's non-traditional geometric representation of a unit fraction, a variety of learning environments that lead to the enrichment of mathematics for teaching can be developed. The…

In the Minds of OSCE Examiners: Uncovering Hidden Assumptions

ERIC Educational Resources Information Center

Chahine, Saad; Holmes, Bruce; Kowalewski, Zbigniew

2016-01-01

The Objective Structured Clinical Exam (OSCE) is a widely used method of assessment in medical education. Rater cognition has become an important area of inquiry in the medical education assessment literature generally, and in the OSCE literature specifically, because of concerns about potential compromises of validity. In this study, a novel…

Sexual Harassment and Abuse of Adolescent Schoolgirls in South India

ERIC Educational Resources Information Center

Leach, Fiona; Sitaram, Shashikala

2007-01-01

This article reports on a small exploratory study of adolescent girls' experiences of sexual harassment and abuse while attending secondary school in Karnataka State, South India. In South Asia, public discussion of sexual matters, especially relating to children, is largely taboo, and the study uncovers a hidden aspect of schooling, which…

Reporting on Race, Education & No Child Left Behind: A Guide for Journalists.

ERIC Educational Resources Information Center

Johnson, Tammy, Ed.

This handbook is a tool that reporters can use to uncover the hidden dimensions of race in public education and ask the right questions about the No Child Left Behind Act of 2001. Section 1, "Race Revealed", includes "Special Education" (Daniel J. Losen); "Dropout and Graduation Rates" (Daniel J. Losen);…

Novel Insights into the Transcriptome of Dirofilaria immitis

PubMed Central

Zhang, Zhihe; Hou, Rong; Wu, Xuhang; Yang, Deying; Zhang, Runhui; Zheng, Wanpeng; Nie, Huaming; Xie, Yue; Yan, Ning; Yang, Zhi; Wang, Chengdong; Luo, Li; Liu, Li; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

2012-01-01

Background The heartworm Dirofilaria immitis is the causal agent of cardiopulmonary dirofilariosis in dogs and cats, and also infects a wide range of wild mammals as well as humans. One bottleneck for the design of fundamentally new intervention and management strategies against D. immitis may be the currently limited knowledge of fundamental molecular aspects of D. immitis. Methodology/Principal Findings A next-generation sequencing platform combining computational approaches was employed to assess a global view of the heartworm transcriptome. A total of 20,810 unigenes (mean length  = 1,270 bp) were assembled from 22.3 million clean reads. From these, 15,698 coding sequences (CDS) were inferred, and about 85% of the unigenes had orthologs/homologs in public databases. Comparative transcriptomic study uncovered 4,157 filarial-specific genes as well as 3,795 genes potentially involved in filarial-Wolbachia symbiosis. In addition, the potential intestine transcriptome of D. immitis (1,101 genes) was mined for the first time, which might help to discover ‘hidden antigens’. Conclusions/Significance This study provides novel insights into the transcriptome of D. immitis and sheds light on its molecular processes and survival mechanisms. Furthermore, it provides a platform to discover new vaccine candidates and potential targets for new drugs against dirofilariosis. PMID:22911833

[Further Distinctions between Magic, Reality, Religion, and Fiction. Commentaries.

ERIC Educational Resources Information Center

Boyer, Pascal; Taylor, Marjorie; Harris, Paul L.; Chandler, Michael; Johnson, Carl N.

1997-01-01

Contains the following commentaries: "Further Distinctions between Magic, Reality, Religion, and Fiction"; "The Role of Creative Control and Culture in Children's Fantasy/Reality Judgments"; "The Last of the Magicians? Children, Scientists, and the Invocation of Hidden Causal Powers"; "Rescuing Magical Thinking…

Uncovering the wisdom hidden between the lines: the Collaborative Reflexive Deliberative Approach.

PubMed

Crabtree, Benjamin F; Miller, William L; Gunn, Jane M; Hogg, William E; Scott, Cathie M; Levesque, Jean-Frederic; Harris, Mark F; Chase, Sabrina M; Advocat, Jenny R; Halma, Lisa M; Russell, Grant M

2018-05-23

Meta-analysis and meta-synthesis have been developed to synthesize results across published studies; however, they are still largely grounded in what is already published, missing the tacit 'between the lines' knowledge generated during many research projects that are not intrinsic to the main objectives of studies. To develop a novel approach to expand and deepen meta-syntheses using researchers' experience, tacit knowledge and relevant unpublished materials. We established new collaborations among primary health care researchers from different contexts based on common interests in reforming primary care service delivery and a diversity of perspectives. Over 2 years, the team met face-to-face and via tele- and video-conferences to employ the Collaborative Reflexive Deliberative Approach (CRDA) to discuss and reflect on published and unpublished results from participants' studies to identify new patterns and insights. CRDA focuses on uncovering critical insights, interpretations hidden within multiple research contexts. For the process to work, careful attention must be paid to ensure sufficient diversity among participants while also having people who are able to collaborate effectively. Ensuring there are enough studies for contextual variation also matters. It is necessary to balance rigorous facilitation techniques with the creation of safe space for diverse contributions. The CRDA requires large commitments of investigator time, the expense of convening facilitated retreats, considerable coordination, and strong leadership. The process creates an environment where interactions among diverse participants can illuminate hidden information within the contexts of studies, effectively enhancing theory development and generating new research questions and strategies.

Hidden Stories: Uncovering the Visual Metaphor for Education and Communication

ERIC Educational Resources Information Center

Hube, Amy M.; Tremblay, Kenneth R., Jr.; Leigh, Katharine E.

2015-01-01

Design solutions have become increasingly complex and based on a rapidly growing body of knowledge. In order to articulate a design solution to a client, the graphic use of the design narrative can effectively communicate complex ideas. Two case study interventions were conducted in an interior design program in which students were introduced to…

Pragmatism and Progressivism in the Educational Thought and Practices of Booker T. Washington

ERIC Educational Resources Information Center

Chennault, Ronald E.

2013-01-01

The author of this article asserts that African-American author and educator Booker T. Washington's work situates him within the educational traditions of pragmatism and progressivism. The article uncovers some of Washington's hidden complexity by drawing upon and extending arguments for labeling him both an educational pragmatist and…

"Things Fall Apart so They Can Fall Together": Uncovering the Hidden Side of Writing a Teaching Award Application

ERIC Educational Resources Information Center

McCormack, Coralie; Vanags, Thea; Prior, Robyn

2014-01-01

Teaching awards are now common practice in higher education. However, few award applicants and their writing guides have investigated their experience of writing a teaching award application, a writing process recognised as different from that required in research publication. To systematically research and analyse their personal experiences two…

A Quantitative Analysis of Organizational Factors That Relate to Data Mining Success

ERIC Educational Resources Information Center

Huebner, Richard A.

2017-01-01

The ubiquity of data in various forms has fueled the need for advanced data-mining techniques within organizations. The advent of data mining methods used to uncover hidden nuggets of information buried within large data sets has also fueled the need for determining how these unique projects can be successful. There are many challenges associated…

Uncovering Hidden Dimensions of Australian Early Childhood Policy History: Insights from Interviews with Policy "Elites"

ERIC Educational Resources Information Center

Logan, Helen; Sumsion, Jennifer; Press, Frances

2014-01-01

This article considers the value of elite interviews as a frequently overlooked methodology in investigations of policymaking in early childhood education and care (ECEC). We contextualise the discussion within a study that examines constructions of quality in Australian ECEC policymaking between 1972 and 2009. We conclude that, despite their…

Smooth information flow in temperature climate network reflects mass transport

NASA Astrophysics Data System (ADS)

Hlinka, Jaroslav; Jajcay, Nikola; Hartman, David; Paluš, Milan

2017-03-01

A directed climate network is constructed by Granger causality analysis of air temperature time series from a regular grid covering the whole Earth. Using winner-takes-all network thresholding approach, a structure of a smooth information flow is revealed, hidden to previous studies. The relevance of this observation is confirmed by comparison with the air mass transfer defined by the wind field. Their close relation illustrates that although the information transferred due to the causal influence is not a physical quantity, the information transfer is tied to the transfer of mass and energy.

What Is Going on Inside the Arrows? Discovering the Hidden Springs in Causal Models

PubMed Central

Murray-Watters, Alexander; Glymour, Clark

2016-01-01

Using Gebharter's (2014) representation, we consider aspects of the problem of discovering the structure of unmeasured sub-mechanisms when the variables in those sub-mechanisms have not been measured. Exploiting an early insight of Sober's (1998), we provide a correct algorithm for identifying latent, endogenous structure—sub-mechanisms—for a restricted class of structures. The algorithm can be merged with other methods for discovering causal relations among unmeasured variables, and feedback relations between measured variables and unobserved causes can sometimes be learned. PMID:27313331

Causal beliefs about depression in different cultural groups—what do cognitive psychological theories of causal learning and reasoning predict?

PubMed Central

Hagmayer, York; Engelmann, Neele

2014-01-01

Cognitive psychological research focuses on causal learning and reasoning while cognitive anthropological and social science research tend to focus on systems of beliefs. Our aim was to explore how these two types of research can inform each other. Cognitive psychological theories (causal model theory and causal Bayes nets) were used to derive predictions for systems of causal beliefs. These predictions were then applied to lay theories of depression as a specific test case. A systematic literature review on causal beliefs about depression was conducted, including original, quantitative research. Thirty-six studies investigating 13 non-Western and 32 Western cultural groups were analyzed by classifying assumed causes and preferred forms of treatment into common categories. Relations between beliefs and treatment preferences were assessed. Substantial agreement between cultural groups was found with respect to the impact of observable causes. Stress was generally rated as most important. Less agreement resulted for hidden, especially supernatural causes. Causal beliefs were clearly related to treatment preferences in Western groups, while evidence was mostly lacking for non-Western groups. Overall predictions were supported, but there were considerable methodological limitations. Pointers to future research, which may combine studies on causal beliefs with experimental paradigms on causal reasoning, are given. PMID:25505432

Uncovering the density of nanowire surface trap states hidden in the transient photoconductance.

PubMed

Xu, Qiang; Dan, Yaping

2016-09-21

The gain of nanoscale photoconductors is closely correlated with surface trap states. Mapping out the density of surface trap states in the semiconductor bandgap is crucial for engineering the performance of nanoscale photoconductors. Traditional capacitive techniques for the measurement of surface trap states are not readily applicable to nanoscale devices. Here, we demonstrate a simple technique to extract the information on the density of surface trap states hidden in the transient photoconductance that is widely observed. With this method, we found that the density of surface trap states of a single silicon nanowire is ∼10(12) cm(-2) eV(-1) around the middle of the upper half bandgap.

Self-Efficacy Beliefs and Mental Time Travel Ability: Uncovering a Hidden Relationship in Educational Settings

ERIC Educational Resources Information Center

Eren, Altay

2009-01-01

The aim of this study was threefold: first, it was to explore the profiles of student teachers' mental time travel ability; second, it was to examine the relationship between student teachers' mental time travel ability and self-efficacy beliefs; and third, it was to investigate the role of self-efficacy beliefs in relationship between the past…

Contract Faculty in Canada: Using Access to Information Requests to Uncover Hidden Academics in Canadian Universities

ERIC Educational Resources Information Center

Brownlee, Jamie

2015-01-01

In Canada, universities are undergoing a process of corporatization where business interests, values and practices are assuming a more prominent place in higher education. A key feature of this process has been the changing composition of academic labor. While it is generally accepted that universities are relying more heavily on contract faculty,…

Uncovering a Hidden Professional Agenda for Teacher Educators: A Mixed Method Study on Flemish Teacher Educators and Their Professional Development

ERIC Educational Resources Information Center

Tack, Hanne; Valcke, Martin; Rots, Isabel; Struyven, Katrien; Vanderlinde, Ruben

2018-01-01

Taking into account the pressing need to understand more about what teacher educators' professional development characterises, this article adopts a mixed method approach to explore Flemish (Dutch-speaking part of Belgium) teacher educators' professional development needs and opportunities. Analysis results of a large-scale survey study with 611…

What Constitutes Science and Scientific Evidence: Roles of Null Hypothesis Testing

ERIC Educational Resources Information Center

Chang, Mark

2017-01-01

We briefly discuss the philosophical basis of science, causality, and scientific evidence, by introducing the hidden but most fundamental principle of science: the similarity principle. The principle's use in scientific discovery is illustrated with Simpson's paradox and other examples. In discussing the value of null hypothesis statistical…

Sniffing out the Secret Poison: Selection Bias in Educational Research

ERIC Educational Resources Information Center

Showalter, Daniel A.; Mullet, Luke B.

2017-01-01

Selection bias is a persistent, and often hidden, problem in educational research. It is the primary obstacle standing in between increasingly available large education datasets and the ability to make valid causal inferences to inform policymaking, research, and practice (Stuart, 2010). This article provides an accessible discussion on the…

Uncovering the wisdom hidden between the lines: the Collaborative Reflexive Deliberative Approach

PubMed Central

Crabtree, Benjamin F; Miller, William L; Gunn, Jane M; Hogg, William E; Scott, Cathie M; Levesque, Jean-Frederic; Harris, Mark F; Chase, Sabrina M; Advocat, Jenny R; Halma, Lisa M; Russell, Grant M

2018-01-01

Abstract Background Meta-analysis and meta-synthesis have been developed to synthesize results across published studies; however, they are still largely grounded in what is already published, missing the tacit ‘between the lines’ knowledge generated during many research projects that are not intrinsic to the main objectives of studies. Objective To develop a novel approach to expand and deepen meta-syntheses using researchers’ experience, tacit knowledge and relevant unpublished materials. Methods We established new collaborations among primary health care researchers from different contexts based on common interests in reforming primary care service delivery and a diversity of perspectives. Over 2 years, the team met face-to-face and via tele- and video-conferences to employ the Collaborative Reflexive Deliberative Approach (CRDA) to discuss and reflect on published and unpublished results from participants’ studies to identify new patterns and insights. Results CRDA focuses on uncovering critical insights, interpretations hidden within multiple research contexts. For the process to work, careful attention must be paid to ensure sufficient diversity among participants while also having people who are able to collaborate effectively. Ensuring there are enough studies for contextual variation also matters. It is necessary to balance rigorous facilitation techniques with the creation of safe space for diverse contributions. Conclusions The CRDA requires large commitments of investigator time, the expense of convening facilitated retreats, considerable coordination, and strong leadership. The process creates an environment where interactions among diverse participants can illuminate hidden information within the contexts of studies, effectively enhancing theory development and generating new research questions and strategies. PMID:29069335

John S. Bell's concept of local causality

NASA Astrophysics Data System (ADS)

Norsen, Travis

2011-12-01

John Stewart Bell's famous theorem is widely regarded as one of the most important developments in the foundations of physics. Yet even as we approach the 50th anniversary of Bell's discovery, its meaning and implications remain controversial. Many workers assert that Bell's theorem refutes the possibility suggested by Einstein, Podolsky, and Rosen (EPR) of supplementing ordinary quantum theory with ``hidden'' variables that might restore determinism and/or some notion of an observer-independent reality. But Bell himself interpreted the theorem very differently--as establishing an ``essential conflict'' between the well-tested empirical predictions of quantum theory and relativistic local causality. Our goal is to make Bell's own views more widely known and to explain Bell's little-known formulation of the concept of relativistic local causality on which his theorem rests. We also show precisely how Bell's formulation of local causality can be used to derive an empirically testable Bell-type inequality and to recapitulate the EPR argument.

John S. Bell's concept of local causality

NASA Astrophysics Data System (ADS)

Norsen, Travis

2011-12-01

John Stewart Bell's famous theorem is widely regarded as one of the most important developments in the foundations of physics. Yet even as we approach the 50th anniversary of Bell's discovery, its meaning and implications remain controversial. Many workers assert that Bell's theorem refutes the possibility suggested by Einstein, Podolsky, and Rosen (EPR) of supplementing ordinary quantum theory with "hidden" variables that might restore determinism and/or some notion of an observer-independent reality. But Bell himself interpreted the theorem very differently—as establishing an "essential conflict" between the well-tested empirical predictions of quantum theory and relativistic local causality. Our goal is to make Bell's own views more widely known and to explain Bell's little-known formulation of the concept of relativistic local causality on which his theorem rests. We also show precisely how Bell's formulation of local causality can be used to derive an empirically testable Bell-type inequality and to recapitulate the EPR argument.

Generalised filtering and stochastic DCM for fMRI.

PubMed

Li, Baojuan; Daunizeau, Jean; Stephan, Klaas E; Penny, Will; Hu, Dewen; Friston, Karl

2011-09-15

This paper is about the fitting or inversion of dynamic causal models (DCMs) of fMRI time series. It tries to establish the validity of stochastic DCMs that accommodate random fluctuations in hidden neuronal and physiological states. We compare and contrast deterministic and stochastic DCMs, which do and do not ignore random fluctuations or noise on hidden states. We then compare stochastic DCMs, which do and do not ignore conditional dependence between hidden states and model parameters (generalised filtering and dynamic expectation maximisation, respectively). We first characterise state-noise by comparing the log evidence of models with different a priori assumptions about its amplitude, form and smoothness. Face validity of the inversion scheme is then established using data simulated with and without state-noise to ensure that DCM can identify the parameters and model that generated the data. Finally, we address construct validity using real data from an fMRI study of internet addiction. Our analyses suggest the following. (i) The inversion of stochastic causal models is feasible, given typical fMRI data. (ii) State-noise has nontrivial amplitude and smoothness. (iii) Stochastic DCM has face validity, in the sense that Bayesian model comparison can distinguish between data that have been generated with high and low levels of physiological noise and model inversion provides veridical estimates of effective connectivity. (iv) Relaxing conditional independence assumptions can have greater construct validity, in terms of revealing group differences not disclosed by variational schemes. Finally, we note that the ability to model endogenous or random fluctuations on hidden neuronal (and physiological) states provides a new and possibly more plausible perspective on how regionally specific signals in fMRI are generated. Copyright © 2011. Published by Elsevier Inc.

Uncovering the Hidden Wage : Public Perceptions of Opportunities for Side Income in Various Occupations in the USSR

DTIC Science & Technology

1991-11-01

34 February 1991.31 pp. 26. Kevin Block. "Depoliticizing Ownership: An Examination of the Property Reform Debate and the New Law on Ownership in the USSR...RSFSR (Trud v SSSR, pp. 156-157). 18 Assuming librariam make the average of waer in "Cultme" (and they pulably made less), the official salary of a

Troublesome aspects of the Renyi-MaxEnt treatment.

PubMed

Plastino, A; Rocca, M C; Pennini, F

2016-07-01

We study in great detail the possible existence of a Renyi-associated thermodynamics, with negative results. In particular, we uncover a hidden relation in Renyi's variational problem (MaxEnt). This relation connects the two associated Lagrange multipliers (canonical ensemble) with the mean energy 〈U〉 and the Renyi parameter α. As a consequence of such relation, we obtain anomalous Renyi-MaxEnt thermodynamic results.

PPARα siRNA–Treated Expression Profiles Uncover the Causal Sufficiency Network for Compound-Induced Liver Hypertrophy

PubMed Central

Dai, Xudong; Souza, Angus T. De; Dai, Hongyue; Lewis, David L; Lee, Chang-kyu; Spencer, Andy G; Herweijer, Hans; Hagstrom, Jim E; Linsley, Peter S; Bassett, Douglas E; Ulrich, Roger G; He, Yudong D

2007-01-01

Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an effective tool in unveiling the genes essential for specific cellular functions and biological activities. However, eliciting the relative contribution of and sufficiency relationships among the genes identified remains challenging. In the rodent, the most widely used animal model in preclinical studies, it is unrealistic to exhaustively examine all potential interactions by RNAi screening. Application of existing computational approaches to infer regulatory networks with biological outcomes in the rodent is limited by the requirements for a large number of targeted permutations. Therefore, we developed a two-step relay method that requires only one targeted perturbation for genome-wide de novo pathway discovery. Using expression profiles in response to small interfering RNAs (siRNAs) against the gene for peroxisome proliferator-activated receptor α (Ppara), our method unveiled the potential causal sufficiency order network for liver hypertrophy in the rodent. The validity of the inferred 16 causal transcripts or 15 known genes for PPARα-induced liver hypertrophy is supported by their ability to predict non-PPARα–induced liver hypertrophy with 84% sensitivity and 76% specificity. Simulation shows that the probability of achieving such predictive accuracy without the inferred causal relationship is exceedingly small (p < 0.005). Five of the most sufficient causal genes have been previously disrupted in mouse models; the resulting phenotypic changes in the liver support the inferred causal roles in liver hypertrophy. Our results demonstrate the feasibility of defining pathways mediating drug-induced toxicity from siRNA-treated expression profiles. When combined with phenotypic evaluation, our approach should help to unleash the full potential of siRNAs in systematically unveiling the molecular mechanism of biological events. PMID:17335344

Uncovering hidden heterogeneity: Geo-statistical models illuminate the fine scale effects of boating infrastructure on sediment characteristics and contaminants.

PubMed

Hedge, L H; Dafforn, K A; Simpson, S L; Johnston, E L

2017-06-30

Infrastructure associated with coastal communities is likely to not only directly displace natural systems, but also leave environmental footprints' that stretch over multiple scales. Some coastal infrastructure will, there- fore, generate a hidden layer of habitat heterogeneity in sediment systems that is not immediately observable in classical impact assessment frameworks. We examine the hidden heterogeneity associated with one of the most ubiquitous coastal modifications; dense swing moorings fields. Using a model based geo-statistical framework we highlight the variation in sedimentology throughout mooring fields and reference locations. Moorings were correlated with patches of sediment with larger particle sizes, and associated metal(loid) concentrations in these patches were depressed. Our work highlights two important ideas i) mooring fields create a mosaic of habitat in which contamination decreases and grain sizes increase close to moorings, and ii) model- based frameworks provide an information rich, easy-to-interpret way to communicate complex analyses to stakeholders. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Data-based reconstruction of complex geospatial networks, nodal positioning and detection of hidden nodes

PubMed Central

Su, Ri-Qi; Wang, Wen-Xu; Wang, Xiao; Lai, Ying-Cheng

2016-01-01

Given a complex geospatial network with nodes distributed in a two-dimensional region of physical space, can the locations of the nodes be determined and their connection patterns be uncovered based solely on data? We consider the realistic situation where time series/signals can be collected from a single location. A key challenge is that the signals collected are necessarily time delayed, due to the varying physical distances from the nodes to the data collection centre. To meet this challenge, we develop a compressive-sensing-based approach enabling reconstruction of the full topology of the underlying geospatial network and more importantly, accurate estimate of the time delays. A standard triangularization algorithm can then be employed to find the physical locations of the nodes in the network. We further demonstrate successful detection of a hidden node (or a hidden source or threat), from which no signal can be obtained, through accurate detection of all its neighbouring nodes. As a geospatial network has the feature that a node tends to connect with geophysically nearby nodes, the localized region that contains the hidden node can be identified. PMID:26909187

Variables in psychology: a critique of quantitative psychology.

PubMed

Toomela, Aaro

2008-09-01

Mind is hidden from direct observation; it can be studied only by observing behavior. Variables encode information about behaviors. There is no one-to-one correspondence between behaviors and mental events underlying the behaviors, however. In order to understand mind it would be necessary to understand exactly what information is represented in variables. This aim cannot be reached after variables are already encoded. Therefore, statistical data analysis can be very misleading in studies aimed at understanding mind that underlies behavior. In this article different kinds of information that can be represented in variables are described. It is shown how informational ambiguity of variables leads to problems of theoretically meaningful interpretation of the results of statistical data analysis procedures in terms of hidden mental processes. Reasons are provided why presence of dependence between variables does not imply causal relationship between events represented by variables and absence of dependence between variables cannot rule out the causal dependence of events represented by variables. It is concluded that variable-psychology has a very limited range of application for the development of a theory of mind-psychology.

Uncovering the Hidden Molecular Signatures of Breast Cancer

DTIC Science & Technology

2013-05-01

that! synergy! between! the! oncogene!MET!and!loss!of!p53!(tumor! protein !p53)!lead!to!a!tumor!phenotype!that! reflects! the! human! claudinDlow...membrane! protein ! levels! increase! continuously! in! accordance.! This! increase! has! been! directly! linked! to! a! corresponding! change! in...the!ESR! protein ! (Figure!1).!Alternatively,!a!signature!may! order!patients!in!such!a!way!that!associations!can!be!made!with!a!variety!of!other

Uncovering the Hidden Histories: Black and Asian People in the Two World Wars

ERIC Educational Resources Information Center

Gaze, Rupert

2005-01-01

The stories we tell in history are often stories about ourselves. This can lead to tremendous distortion. Rupert Gaze was shocked when a young black student told him that there was no point in his studying the Second World War because it had nothing to do with him or his family. While Gaze has worked for the Imperial War Museum (IWM) North, it has…

"I Don't Know What Literacy Is": Uncovering Hidden Literacies in a Community Library Using Ecological and Participatory Research Methodologies with Children

ERIC Educational Resources Information Center

Pahl, Kate; Allan, Chloe

2011-01-01

This article describes an ecological study in Eastside, a particular area of Rotherham, a town in the north of England, UK. The purpose of the study was to collect information about literacy practices in a community setting, focusing on a library. The researchers used an ecological approach to data collection. The methodology included approaches…

The War on Schools: NCLB, Nation Creation and the Educational Construction of Whiteness

ERIC Educational Resources Information Center

Leonardo, Zeus

2007-01-01

The study of whiteness in education is receiving increased attention. This essay argues that the No Child Left Behind Act is an example of color-blindness "par excellence." NCLB's hidden referent of whiteness makes a casual pass at racial explanation that sidesteps race as a causal explanation for educational disparities. In this sense,…

Model Selection Approach Suggests Causal Association between 25-Hydroxyvitamin D and Colorectal Cancer

PubMed Central

Theodoratou, Evropi; Farrington, Susan M.; Tenesa, Albert; Dunlop, Malcolm G.; McKeigue, Paul; Campbell, Harry

2013-01-01

Introduction Vitamin D deficiency has been associated with increased risk of colorectal cancer (CRC), but causal relationship has not yet been confirmed. We investigate the direction of causation between vitamin D and CRC by extending the conventional approaches to allow pleiotropic relationships and by explicitly modelling unmeasured confounders. Methods Plasma 25-hydroxyvitamin D (25-OHD), genetic variants associated with 25-OHD and CRC, and other relevant information was available for 2645 individuals (1057 CRC cases and 1588 controls) and included in the model. We investigate whether 25-OHD is likely to be causally associated with CRC, or vice versa, by selecting the best modelling hypothesis according to Bayesian predictive scores. We examine consistency for a range of prior assumptions. Results Model comparison showed preference for the causal association between low 25-OHD and CRC over the reverse causal hypothesis. This was confirmed for posterior mean deviances obtained for both models (11.5 natural log units in favour of the causal model), and also for deviance information criteria (DIC) computed for a range of prior distributions. Overall, models ignoring hidden confounding or pleiotropy had significantly poorer DIC scores. Conclusion Results suggest causal association between 25-OHD and colorectal cancer, and support the need for randomised clinical trials for further confirmations. PMID:23717431

Causal tapestries for psychology and physics.

PubMed

Sulis, William H

2012-04-01

Archetypal dynamics is a formal approach to the modeling of information flow in complex systems used to study emergence. It is grounded in the Fundamental Triad of realisation (system), interpretation (archetype) and representation (formal model). Tapestries play a fundamental role in the framework of archetypal dynamics as a formal representational system. They represent information flow by means of multi layered, recursive, interlinked graphical structures that express both geometry (form or sign) and logic (semantics). This paper presents a detailed mathematical description of a specific tapestry model, the causal tapestry, selected for use in describing behaving systems such as appear in psychology and physics from the standpoint of Process Theory. Causal tapestries express an explicit Lorentz invariant transient now generated by means of a reality game. Observables are represented by tapestry informons while subjective or hidden components (for example intellectual and emotional processes) are incorporated into the reality game that determines the tapestry dynamics. As a specific example, we formulate a random graphical dynamical system using causal tapestries.

Folksonomies and clustering in the collaborative system CiteULike

NASA Astrophysics Data System (ADS)

Capocci, Andrea; Caldarelli, Guido

2008-06-01

We analyze CiteULike, an online collaborative tagging system where users bookmark and annotate scientific papers. Such a system can be naturally represented as a tri-partite graph whose nodes represent papers, users and tags connected by individual tag assignments. The semantics of tags is studied here, in order to uncover the hidden relationships between tags. We find that the clustering coefficient can be used to analyze the semantical patterns among tags.

Bacillus thuringiensis toxin resistance mechanisms among Lepidoptera: progress on genomic approaches to uncover causal mutations in the European corn borer, Ostrinia nubilalis

USDA-ARS?s Scientific Manuscript database

Transgenic plants that expressed Bacillus thuringiensis (Bt) crystalline (Cry) protein toxins can suffer feeding damage from a small number of lepidopteran insect species under field conditions, which has heightened concerns about the durability of pest control tactics. Genomics research has provid...

You've got to know the rules to play the game: how medical students negotiate the hidden curriculum of surgical careers.

PubMed

Hill, Elspeth; Bowman, Katherine; Stalmeijer, Renée; Hart, Jo

2014-09-01

The hidden curriculum may be framed as the culture, beliefs and behaviours of a community that are passed to students outside formal course offerings. Medical careers involve diverse specialties, each with a different culture, yet how medical students negotiate these cultures has not been fully explored. Using surgery as a case study, we aimed to establish, first, whether a specialty-specific hidden curriculum existed for students, and second, how students encountered and negotiated surgical career options. Using a constructivist grounded theory approach, we explored students' thoughts, beliefs and experiences regarding career decisions and surgery. An exploratory questionnaire informed the discussion schedule for semi-structured individual interviews. Medical students were purposively sampled by year group, gender and career intentions in surgery. Data collection and analysis were iterative: analysis followed each interview and guided the adaptation of our discussion schedule to further our evolving model. Students held a clear sense of a hidden curriculum in surgery. To successfully negotiate a surgical career, students perceived that they must first build networks because careers information flows through relationships. They subsequently enacted what they learned by accruing the accolades ('ticking the boxes') and appropriating the dispositions ('walking the talk') of 'future surgeons'. This allowed them to identify themselves and to be identified by others as 'future surgeons' and to gain access to participation in the surgical world. Participation then enabled further network building and access to careers information in a positive feedback loop. For some, negotiating the hidden curriculum was more difficult, which, for them, rendered a surgical career unattractive or unattainable. Students perceive a clear surgery-specific hidden curriculum. Using a constructivist grounded theory approach, we have developed a model of how students encounter, uncover and enact this hidden curriculum to succeed. Drawing on concepts of Bourdieu, we discuss unequal access to the hidden curriculum, which was found to exclude many from the possibility of a surgical career. © 2014 John Wiley & Sons Ltd.

Empirical Benchmarks of Hidden Bias in Educational Research: Implication for Assessing How well Propensity Score Methods Approximate Experiments and Conducting Sensitivity Analysis

ERIC Educational Resources Information Center

Dong, Nianbo; Lipsey, Mark

2014-01-01

When randomized control trials (RCT) are not feasible, researchers seek other methods to make causal inference, e.g., propensity score methods. One of the underlined assumptions for the propensity score methods to obtain unbiased treatment effect estimates is the ignorability assumption, that is, conditional on the propensity score, treatment…

Conservative forgetful scholars: How people learn causal structure through sequences of interventions.

PubMed

Bramley, Neil R; Lagnado, David A; Speekenbrink, Maarten

2015-05-01

Interacting with a system is key to uncovering its causal structure. A computational framework for interventional causal learning has been developed over the last decade, but how real causal learners might achieve or approximate the computations entailed by this framework is still poorly understood. Here we describe an interactive computer task in which participants were incentivized to learn the structure of probabilistic causal systems through free selection of multiple interventions. We develop models of participants' intervention choices and online structure judgments, using expected utility gain, probability gain, and information gain and introducing plausible memory and processing constraints. We find that successful participants are best described by a model that acts to maximize information (rather than expected score or probability of being correct); that forgets much of the evidence received in earlier trials; but that mitigates this by being conservative, preferring structures consistent with earlier stated beliefs. We explore 2 heuristics that partly explain how participants might be approximating these models without explicitly representing or updating a hypothesis space. (c) 2015 APA, all rights reserved).

Uncovering hidden variation in polyploid wheat.

PubMed

Krasileva, Ksenia V; Vasquez-Gross, Hans A; Howell, Tyson; Bailey, Paul; Paraiso, Francine; Clissold, Leah; Simmonds, James; Ramirez-Gonzalez, Ricardo H; Wang, Xiaodong; Borrill, Philippa; Fosker, Christine; Ayling, Sarah; Phillips, Andrew L; Uauy, Cristobal; Dubcovsky, Jorge

2017-02-07

Comprehensive reverse genetic resources, which have been key to understanding gene function in diploid model organisms, are missing in many polyploid crops. Young polyploid species such as wheat, which was domesticated less than 10,000 y ago, have high levels of sequence identity among subgenomes that mask the effects of recessive alleles. Such redundancy reduces the probability of selection of favorable mutations during natural or human selection, but also allows wheat to tolerate high densities of induced mutations. Here we exploited this property to sequence and catalog more than 10 million mutations in the protein-coding regions of 2,735 mutant lines of tetraploid and hexaploid wheat. We detected, on average, 2,705 and 5,351 mutations per tetraploid and hexaploid line, respectively, which resulted in 35-40 mutations per kb in each population. With these mutation densities, we identified an average of 23-24 missense and truncation alleles per gene, with at least one truncation or deleterious missense mutation in more than 90% of the captured wheat genes per population. This public collection of mutant seed stocks and sequence data enables rapid identification of mutations in the different copies of the wheat genes, which can be combined to uncover previously hidden variation. Polyploidy is a central phenomenon in plant evolution, and many crop species have undergone recent genome duplication events. Therefore, the general strategy and methods developed herein can benefit other polyploid crops.

The metaphorical and mythical use of the kidney in antiquity.

PubMed

Maio, G

1999-01-01

While the Syrians and the Arabs viewed the liver as the center of life, the kidneys, in contrast, held a primary place of importance in Israel. In Hebrew tradition, they were considered to be the most important internal organs along with the heart. In the Old Testament most frequently the kidneys are associated with the most inner stirrings of emotional life. But they are also viewed as the seat of the secret thoughts of the human; they are used as an omen metaphor, as a metaphor for moral discernment, for reflection and inspiration. This field of tension in metaphoric usage is resolved under the conception of the kidneys as life center. In the Old Testament the kidneys thus are primarily used as metaphor for the core of the person, for the area of greatest vulnerability. For us today, this metaphorical use of the kidneys has lost its meaning. One reason for its disappearance is certainly the monopoly of causal-analytic rationality in science of today. The kidney has developed from myth to organ, and with this transition a variety of perspectives and ways of looking at knowledge inherent in imaginative thought have been lost. But the metaphor uncovers a deeper level of truth, it represents another form of reconstruction of reality which needs not necessarily be subordinate to the scientific rationality. Today as well, these imaginative ideas can provide an approach to an essential level of reality which may otherwise remain hidden.

Modeling emergent border-crossing behaviors during pandemics

NASA Astrophysics Data System (ADS)

Santos, Eunice E.; Santos, Eugene; Korah, John; Thompson, Jeremy E.; Gu, Qi; Kim, Keum Joo; Li, Deqing; Russell, Jacob; Subramanian, Suresh; Zhang, Yuxi; Zhao, Yan

2013-06-01

Modeling real-world scenarios is a challenge for traditional social science researchers, as it is often hard to capture the intricacies and dynamisms of real-world situations without making simplistic assumptions. This imposes severe limitations on the capabilities of such models and frameworks. Complex population dynamics during natural disasters such as pandemics is an area where computational social science can provide useful insights and explanations. In this paper, we employ a novel intent-driven modeling paradigm for such real-world scenarios by causally mapping beliefs, goals, and actions of individuals and groups to overall behavior using a probabilistic representation called Bayesian Knowledge Bases (BKBs). To validate our framework we examine emergent behavior occurring near a national border during pandemics, specifically the 2009 H1N1 pandemic in Mexico. The novelty of the work in this paper lies in representing the dynamism at multiple scales by including both coarse-grained (events at the national level) and finegrained (events at two separate border locations) information. This is especially useful for analysts in disaster management and first responder organizations who need to be able to understand both macro-level behavior and changes in the immediate vicinity, to help with planning, prevention, and mitigation. We demonstrate the capabilities of our framework in uncovering previously hidden connections and explanations by comparing independent models of the border locations with their fused model to identify emergent behaviors not found in either independent location models nor in a simple linear combination of those models.

Transcriptome analysis of a Ustilago maydis ust1 deletion mutant uncovers involvement of laccase and polyketide synthase genes in spore development

USDA-ARS?s Scientific Manuscript database

Ustilago maydis, causal agent of corn smut disease, is a dimorphic fungus alternating between a saprobic budding haploid, and an obligate pathogenic filamentous dikaryon. Maize responds to U. maydis colonization by producing tumorous structures, and only within these does the fungus sporulate, produ...

Development of Young Children's Understanding that the Recent Past Is Causally Bound to the Present.

ERIC Educational Resources Information Center

Povinelli, Daniel J.; Landry, Anita M.; Theall, Laura A.; Clark, Britten R.; Castille, Conni M.

1999-01-01

Six experiments examined young children's understanding that very recent past events determine the present. Found that 4-year-olds, but not 3-year-olds, could locate a puppet they had observed being hidden either through a videotape or using a verbal analog of the task. When children observed 2 events in which they participated, only 5-year-olds…

Spatial-temporal causal modeling: a data centric approach to climate change attribution (Invited)

NASA Astrophysics Data System (ADS)

Lozano, A. C.

2010-12-01

Attribution of climate change has been predominantly based on simulations using physical climate models. These approaches rely heavily on the employed models and are thus subject to their shortcomings. Given the physical models’ limitations in describing the complex system of climate, we propose an alternative approach to climate change attribution that is data centric in the sense that it relies on actual measurements of climate variables and human and natural forcing factors. We present a novel class of methods to infer causality from spatial-temporal data, as well as a procedure to incorporate extreme value modeling into our methodology in order to address the attribution of extreme climate events. We develop a collection of causal modeling methods using spatio-temporal data that combine graphical modeling techniques with the notion of Granger causality. “Granger causality” is an operational definition of causality from econometrics, which is based on the premise that if a variable causally affects another, then the past values of the former should be helpful in predicting the future values of the latter. In its basic version, our methodology makes use of the spatial relationship between the various data points, but treats each location as being identically distributed and builds a unique causal graph that is common to all locations. A more flexible framework is then proposed that is less restrictive than having a single causal graph common to all locations, while avoiding the brittleness due to data scarcity that might arise if one were to independently learn a different graph for each location. The solution we propose can be viewed as finding a middle ground by partitioning the locations into subsets that share the same causal structures and pooling the observations from all the time series belonging to the same subset in order to learn more robust causal graphs. More precisely, we make use of relationships between locations (e.g. neighboring relationship) by defining a relational graph in which related locations are connected (note that this relational graph, which represents relationships among the different locations, is distinct from the causal graph, which represents causal relationships among the individual variables - e.g. temperature, pressure- within a multivariate time series). We then define a hidden Markov Random Field (hMRF), assigning a hidden state to each node (location), with the state assignment guided by the prior information encoded in the relational graph. Nodes that share the same state in the hMRF model will have the same causal graph. State assignment can thus shed light on unknown relations among locations (e.g. teleconnection). While the model has been described in terms of hard location partitioning to facilitate its exposition, in fact a soft partitioning is maintained throughout learning. This leads to a form of transfer learning, which makes our model applicable even in situations where partitioning the locations might not seem appropriate. We first validate the effectiveness of our methodology on synthetic datasets, and then apply it to actual climate measurement data. The experimental results show that our approach offers a useful alternative to the simulation-based approach for climate modeling and attribution, and has the capability to provide valuable scientific insights from a new perspective.

Causal attributions in Brazilian children's reasoning about health and illness.

PubMed

Boruchovitch, E; Mednick, B R

2000-10-01

At a time when a great number of diseases can be prevented by changing one's habits and life style, investigations have focused on understanding what adults and children believe to be desirable health practices and uncovering the factors associated with successful adherence to such practices. For these, causal attributions for health and illness were investigated among 96 Brazilian elementary school students. Ninety six subjects, aged 6 to 14, were interviewed individually and their causal attributions were assessed through 14 true-false items (e.g. people stay well [healthy] because they are lucky). The relationship between the children's causal attributions and demographic characteristics were also examined. Overall, the results were consistent with previous researches. "Taking care of oneself" was considered the most important cause of good health. "Viruses and germs" and "lack of self-care" were the most selected causes of illness. Analyses revealed significant relationship between subjects' causal attribution and their age, school grade level, socioeconomic status and gender. The study findings suggest that there may be more cross-cultural similarities than differences in children's causal attributions for health and illness. Finding ways to help individuals engage in appropriate preventive-maintenance health practices without developing an exaggerated notion that the individuals can control their own health and illness is a challenge which remains to be addressed by further research.

The way to uncover community structure with core and diversity

NASA Astrophysics Data System (ADS)

Chang, Y. F.; Han, S. K.; Wang, X. D.

2018-07-01

Communities are ubiquitous in nature and society. Individuals that share common properties often self-organize to form communities. Avoiding the shortages of computation complexity, pre-given information and unstable results in different run, in this paper, we propose a simple and efficient method to deepen our understanding of the emergence and diversity of communities in complex systems. By introducing the rational random selection, our method reveals the hidden deterministic and normal diverse community states of community structure. To demonstrate this method, we test it with real-world systems. The results show that our method could not only detect community structure with high sensitivity and reliability, but also provide instructional information about the hidden deterministic community world and the real normal diverse community world by giving out the core-community, the real-community, the tide and the diversity. Thizs is of paramount importance in understanding, predicting, and controlling a variety of collective behaviors in complex systems.

Labeling Actors and Uncovering Causal Accounts of Their States in Social Networks and Social Media

ERIC Educational Resources Information Center

Bui, Ngot P.

2016-01-01

The emergence of social networks and social media has resulted in exponential increase in the amount of data that link diverse types of richly structured digital objects e.g., individuals, articles, images, videos, music, etc. Such data are naturally represented as heterogeneous networks with multiple types of objects e.g., actors, video,…

Learning about causes from people and about people as causes: probabilistic models and social causal reasoning.

PubMed

Buchsbaum, Daphna; Seiver, Elizabeth; Bridgers, Sophie; Gopnik, Alison

2012-01-01

A major challenge children face is uncovering the causal structure of the world around them. Previous research on children's causal inference has demonstrated their ability to learn about causal relationships in the physical environment using probabilistic evidence. However, children must also learn about causal relationships in the social environment, including discovering the causes of other people's behavior, and understanding the causal relationships between others' goal-directed actions and the outcomes of those actions. In this chapter, we argue that social reasoning and causal reasoning are deeply linked, both in the real world and in children's minds. Children use both types of information together and in fact reason about both physical and social causation in fundamentally similar ways. We suggest that children jointly construct and update causal theories about their social and physical environment and that this process is best captured by probabilistic models of cognition. We first present studies showing that adults are able to jointly infer causal structure and human action structure from videos of unsegmented human motion. Next, we describe how children use social information to make inferences about physical causes. We show that the pedagogical nature of a demonstrator influences children's choices of which actions to imitate from within a causal sequence and that this social information interacts with statistical causal evidence. We then discuss how children combine evidence from an informant's testimony and expressed confidence with evidence from their own causal observations to infer the efficacy of different potential causes. We also discuss how children use these same causal observations to make inferences about the knowledge state of the social informant. Finally, we suggest that psychological causation and attribution are part of the same causal system as physical causation. We present evidence that just as children use covariation between physical causes and their effects to learn physical causal relationships, they also use covaration between people's actions and the environment to make inferences about the causes of human behavior.

Entrepreneurial Regions: Do Macro-Psychological Cultural Characteristics of Regions Help Solve the "Knowledge Paradox" of Economics?

PubMed

Obschonka, Martin; Stuetzer, Michael; Gosling, Samuel D; Rentfrow, Peter J; Lamb, Michael E; Potter, Jeff; Audretsch, David B

2015-01-01

In recent years, modern economies have shifted away from being based on physical capital and towards being based on new knowledge (e.g., new ideas and inventions). Consequently, contemporary economic theorizing and key public policies have been based on the assumption that resources for generating knowledge (e.g., education, diversity of industries) are essential for regional economic vitality. However, policy makers and scholars have discovered that, contrary to expectations, the mere presence of, and investments in, new knowledge does not guarantee a high level of regional economic performance (e.g., high entrepreneurship rates). To date, this "knowledge paradox" has resisted resolution. We take an interdisciplinary perspective to offer a new explanation, hypothesizing that "hidden" regional culture differences serve as a crucial factor that is missing from conventional economic analyses and public policy strategies. Focusing on entrepreneurial activity, we hypothesize that the statistical relation between knowledge resources and entrepreneurial vitality (i.e., high entrepreneurship rates) in a region will depend on "hidden" regional differences in entrepreneurial culture. To capture such "hidden" regional differences, we derive measures of entrepreneurship-prone culture from two large personality datasets from the United States (N = 935,858) and Great Britain (N = 417,217). In both countries, the findings were consistent with the knowledge-culture-interaction hypothesis. A series of nine additional robustness checks underscored the robustness of these results. Naturally, these purely correlational findings cannot provide direct evidence for causal processes, but the results nonetheless yield a remarkably consistent and robust picture in the two countries. In doing so, the findings raise the idea of regional culture serving as a new causal candidate, potentially driving the knowledge paradox; such an explanation would be consistent with research on the psychological characteristics of entrepreneurs.

Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage.

PubMed

Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E Sander; Kleinberg, Samantha

2016-01-01

High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology.

Identification and Sensitivity Analysis for Average Causal Mediation Effects with Time-Varying Treatments and Mediators: Investigating the Underlying Mechanisms of Kindergarten Retention Policy.

PubMed

Park, Soojin; Steiner, Peter M; Kaplan, David

2018-06-01

Considering that causal mechanisms unfold over time, it is important to investigate the mechanisms over time, taking into account the time-varying features of treatments and mediators. However, identification of the average causal mediation effect in the presence of time-varying treatments and mediators is often complicated by time-varying confounding. This article aims to provide a novel approach to uncovering causal mechanisms in time-varying treatments and mediators in the presence of time-varying confounding. We provide different strategies for identification and sensitivity analysis under homogeneous and heterogeneous effects. Homogeneous effects are those in which each individual experiences the same effect, and heterogeneous effects are those in which the effects vary over individuals. Most importantly, we provide an alternative definition of average causal mediation effects that evaluates a partial mediation effect; the effect that is mediated by paths other than through an intermediate confounding variable. We argue that this alternative definition allows us to better assess at least a part of the mediated effect and provides meaningful and unique interpretations. A case study using ECLS-K data that evaluates kindergarten retention policy is offered to illustrate our proposed approach.

A Game of Hide and Seek: Expectations of Clumpy Resources Influence Hiding and Searching Patterns

PubMed Central

Wilke, Andreas; Minich, Steven; Panis, Megane; Langen, Tom A.; Skufca, Joseph D.; Todd, Peter M.

2015-01-01

Resources are often distributed in clumps or patches in space, unless an agent is trying to protect them from discovery and theft using a dispersed distribution. We uncover human expectations of such spatial resource patterns in collaborative and competitive settings via a sequential multi-person game in which participants hid resources for the next participant to seek. When collaborating, resources were mostly hidden in clumpy distributions, but when competing, resources were hidden in more dispersed (random or hyperdispersed) patterns to increase the searching difficulty for the other player. More dispersed resource distributions came at the cost of higher overall hiding (as well as searching) times, decreased payoffs, and an increased difficulty when the hider had to recall earlier hiding locations at the end of the experiment. Participants’ search strategies were also affected by their underlying expectations, using a win-stay lose-shift strategy appropriate for clumpy resources when searching for collaboratively-hidden items, but moving equally far after finding or not finding an item in competitive settings, as appropriate for dispersed resources. Thus participants showed expectations for clumpy versus dispersed spatial resources that matched the distributions commonly found in collaborative versus competitive foraging settings. PMID:26154661

A chemical family-based strategy for uncovering hidden bioactive molecules and multicomponent interactions in herbal medicines.

PubMed

Song, Hui-Peng; Wu, Si-Qi; Hao, Haiping; Chen, Jun; Lu, Jun; Xu, Xiaojun; Li, Ping; Yang, Hua

2016-03-30

Two concepts involving natural products were proposed and demonstrated in this paper. (1) Natural product libraries (e.g. herbal extract) are not perfect for bioactivity screening because of the vast complexity of compound compositions, and thus a library reconstruction procedure is necessary before screening. (2) The traditional mode of "screening single compound" could be improved to "screening single compound, drug combination and multicomponent interaction" due to the fact that herbal medicines work by integrative effects of multi-components rather than single effective constituents. Based on the two concepts, we established a novel strategy aiming to make screening easier and deeper. Using thrombin as the model enzyme, we firstly uncovered the minor lead compounds, potential drug combinations and multicomponent interactions in an herbal medicine of Dan-Qi pair, showing a significant advantage over previous methods. This strategy was expected to be a new and promising mode for investigation of herbal medicines.

Uncovering the hidden iceberg structure of the Galactic halo

NASA Astrophysics Data System (ADS)

Moss, Vanessa A.; Di Teodoro, Enrico M.; McClure-Griffiths, Naomi M.; Lockman, Felix; Pisano, D. J.; Price, Daniel; Rees, Glen

2018-01-01

How the Milky Way gets its gas and keeps its measured star formation rate going are both long-standing mysteries in Galactic studies, with important implications for galaxy evolution across the Universe. I will present our recent discovery of two populations of neutral hydrogen (HI) in the halo of the Milky Way: 1) a narrow line-width dense population typical of the majority of bright high velocity cloud (HVC) components, and 2) a fainter, broad line-width diffuse population that aligns well with the population found in very sensitive pointings such as in Lockman et al. (2002). From our existing data, we concluded that the diffuse population likely outweighs the dense HI by a factor of 3. This discovery of diffuse HI, which appears to be prevalent throughout the halo, takes us closer to solving the Galactic mystery of accretion and reveals a gaseous neutral halo hidden from the view of most large-scale surveys. We are currently carrying out deep Parkes observations to investigate these results further, in order to truly uncover the nature of the diffuse HI and determine whether our 3:1 ratio (based on the limited existing data) is consistent with what is seen when Parkes and the 140 ft Green Bank telescope are employed at comparable sensitivity. With these data, through a combination of both known and new sightline measurements, we aim to reveal the structure of the Galactic halo in more detail than ever before.

Hidden consequences of political efficacy: Testing an efficacy-apathy model of political mobilization.

PubMed

Osborne, Danny; Yogeeswaran, Kumar; Sibley, Chris G

2015-10-01

Political efficacy-the belief that one can influence politics-is a key predictor of people's involvement in social movements. Political institutions that are open to change should, however, be seen as just. Thus, political efficacy may ironically undermine minority group members' support for collective action by simultaneously increasing their belief in the fairness of the system. The current study aims to examine this possibility in a national sample of Māori-New Zealand's indigenous minority population. Participants (N = 399) were Māori (Mage = 44.22; SD = 13.30) women (n = 272) and men (n = 115; unreported = 12) who completed a survey assessing their levels of (a) political efficacy, (b) system justification, and (c) support for the political mobilization of their group, as well as relevant demographic covariates. Consistent with past research, political efficacy had a positive direct effect on participants' support for the political mobilization of Māori. Nevertheless, political efficacy also had a negative indirect effect on political mobilization support via increases in system justification. These results held after controlling for participants' ethnic identification, self-efficacy, and conservatism. Our findings uncover a hidden consequence of political efficacy and show that, while believing that the political system is receptive to change predicts political mobilization, it can also undermine minorities' support for the mobilization of their group. Thus, our results uncover a previously unknown process that maintains inequality between ethnic minority and majority group members. (c) 2015 APA, all rights reserved).

Identification of Causal Genes, Networks, and Transcriptional Regulators of REM Sleep and Wake

PubMed Central

Millstein, Joshua; Winrow, Christopher J.; Kasarskis, Andrew; Owens, Joseph R.; Zhou, Lili; Summa, Keith C.; Fitzpatrick, Karrie; Zhang, Bin; Vitaterna, Martha H.; Schadt, Eric E.; Renger, John J.; Turek, Fred W.

2011-01-01

Study Objective: Sleep-wake traits are well-known to be under substantial genetic control, but the specific genes and gene networks underlying primary sleep-wake traits have largely eluded identification using conventional approaches, especially in mammals. Thus, the aim of this study was to use systems genetics and statistical approaches to uncover the genetic networks underlying 2 primary sleep traits in the mouse: 24-h duration of REM sleep and wake. Design: Genome-wide RNA expression data from 3 tissues (anterior cortex, hypothalamus, thalamus/midbrain) were used in conjunction with high-density genotyping to identify candidate causal genes and networks mediating the effects of 2 QTL regulating the 24-h duration of REM sleep and one regulating the 24-h duration of wake. Setting: Basic sleep research laboratory. Patients or Participants: Male [C57BL/6J × (BALB/cByJ × C57BL/6J*) F1] N2 mice (n = 283). Interventions: None. Measurements and Results: The genetic variation of a mouse N2 mapping cross was leveraged against sleep-state phenotypic variation as well as quantitative gene expression measurement in key brain regions using integrative genomics approaches to uncover multiple causal sleep-state regulatory genes, including several surprising novel candidates, which interact as components of networks that modulate REM sleep and wake. In particular, it was discovered that a core network module, consisting of 20 genes, involved in the regulation of REM sleep duration is conserved across the cortex, hypothalamus, and thalamus. A novel application of a formal causal inference test was also used to identify those genes directly regulating sleep via control of expression. Conclusion: Systems genetics approaches reveal novel candidate genes, complex networks and specific transcriptional regulators of REM sleep and wake duration in mammals. Citation: Millstein J; Winrow CJ; Kasarskis A; Owens JR; Zhou L; Summa KC; Fitzpatrick K; Zhang B; Vitaterna MH; Schadt EE; Renger JJ; Turek FW. Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake. SLEEP 2011;34(11):1469-1477. PMID:22043117

Prediction versus aetiology: common pitfalls and how to avoid them.

PubMed

van Diepen, Merel; Ramspek, Chava L; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

2017-04-01

Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre-existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand.In both scientific and clinical practice, however, the two are often confused, resulting in poor-quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Optimal causal filtering for 1 /fα-type noise in single-electrode EEG signals.

PubMed

Paris, Alan; Atia, George; Vosoughi, Azadeh; Berman, Stephen A

2016-08-01

Understanding the mode of generation and the statistical structure of neurological noise is one of the central problems of biomedical signal processing. We have developed a broad class of abstract biological noise sources we call hidden simplicial tissues. In the simplest cases, such tissue emits what we have named generalized van der Ziel-McWhorter (GVZM) noise which has a roughly 1/fα spectral roll-off. Our previous work focused on the statistical structure of GVZM frequency spectra. However, causality of processing operations (i.e., dependence only on the past) is an essential requirement for real-time applications to seizure detection and brain-computer interfacing. In this paper we outline the theoretical background for optimal causal time-domain filtering of deterministic signals embedded in GVZM noise. We present some of our early findings concerning the optimal filtering of EEG signals for the detection of steady-state visual evoked potential (SSVEP) responses and indicate the next steps in our ongoing research.

Causal Modeling the Delayed-Choice Experiment

NASA Astrophysics Data System (ADS)

Chaves, Rafael; Lemos, Gabriela Barreto; Pienaar, Jacques

2018-05-01

Wave-particle duality has become one of the flagships of quantum mechanics. This counterintuitive concept is highlighted in a delayed-choice experiment, where the experimental setup that reveals either the particle or wave nature of a quantum system is decided after the system has entered the apparatus. Here we consider delayed-choice experiments from the perspective of device-independent causal models and show their equivalence to a prepare-and-measure scenario. Within this framework, we consider Wheeler's original proposal and its variant using a quantum control and show that a simple classical causal model is capable of reproducing the quantum mechanical predictions. Nonetheless, among other results, we show that, in a slight variant of Wheeler's gedanken experiment, a photon in an interferometer can indeed generate statistics incompatible with any nonretrocausal hidden variable model, whose dimensionality is the same as that of the quantum system it is supposed to mimic. Our proposal tolerates arbitrary losses and inefficiencies, making it specially suited to loophole-free experimental implementations.

The Brachypodium-Puccinia graminis system: Solving a puzzle to uncover the underlying mechanisms of non-host resistance and plant immunity

USDA-ARS?s Scientific Manuscript database

Brachypodium distachyon is regarded as non-host to the causal agent of stem rust in wheat and barley, P. graminis f. sp. tritici (Pgt), and a near-host to the pathogens of forage grasses, P. graminis f. sp. lolii (Pgl) and P. graminis f. sp. phlei-pratensis (Pgp). Given the devastating effect of ste...

Uncovering cyanobacteria ecological networks from long-term monitoring data using Granger causality analysis

NASA Astrophysics Data System (ADS)

Nelson, N.; Munoz-Carpena, R.; Kaplan, D. A.; Phlips, E. J.

2016-12-01

In many aquatic systems, cyanobacteria form harmful blooms capable of producing toxins, prompting hypoxia, and/or introducing internal nitrogen loads via N2-fixation, among other impacts. Traditionally, system-specific cyanobacteria drivers are determined by performing controlled experiments and bioassays, but these approaches may neglect the influences of confounding factors and over assign importance to only those variables considered within experimental designs. For example, a bioassay may conclude that the cyanobacteria in a particular system are limited by phosphorus, but will not explicitly take into account the role of flow as a control on phosphorus delivery. This study aims to address this analytical gap by identifying environmental controls on cyanobacteria while removing the effects of potentially confounding variables. In the present work, we evaluate a unique long-term (17 year) dataset composed of monthly observations of phytoplankton and zooplankton species abundances, water quality constituents, and hydrologic variables from Lake George, a flow-through lake of the St. Johns River (FL) impacted by cyanobacterial blooms. Using conditional Granger causality analysis, a time series approach that infers causality while removing the effects of confounding variables, data were evaluated to identify biological and physicochemical drivers of cyanobacteria. The analysis was performed for three response variable sets: total cyanobacteria, N2-fixers and non-fixers, and cyanobacteria genera. Results depicted increasing levels of ecological complexity as subdivisions of cyanobacteria became more detailed; whereas causal networks produced from analyses of cyanobacteria genera provided novel insights relevant for management (i.e. nutrients, flow), the total cyanobacteria network only included water temperature as a significant driver. Additionally, the more detailed cyanobacteria subdivisions uncovered that N2-fixation was only evident with the earliest season bloomer, thus indicating that early season bloomers may be facilitating later-season growth. These findings highlight the importance of detailed monitoring efforts, and indicate that greater emphasis needs to be placed on the role of early bloomers in phytoplankton dynamics, as it relates to management efforts.

Spatial-Temporal Synchrophasor Data Characterization and Analytics in Smart Grid Fault Detection, Identification, and Impact Causal Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Huaiguang; Dai, Xiaoxiao; Gao, David Wenzhong

An approach of big data characterization for smart grids (SGs) and its applications in fault detection, identification, and causal impact analysis is proposed in this paper, which aims to provide substantial data volume reduction while keeping comprehensive information from synchrophasor measurements in spatial and temporal domains. Especially, based on secondary voltage control (SVC) and local SG observation algorithm, a two-layer dynamic optimal synchrophasor measurement devices selection algorithm (OSMDSA) is proposed to determine SVC zones, their corresponding pilot buses, and the optimal synchrophasor measurement devices. Combining the two-layer dynamic OSMDSA and matching pursuit decomposition, the synchrophasor data is completely characterized inmore » the spatial-temporal domain. To demonstrate the effectiveness of the proposed characterization approach, SG situational awareness is investigated based on hidden Markov model based fault detection and identification using the spatial-temporal characteristics generated from the reduced data. To identify the major impact buses, the weighted Granger causality for SGs is proposed to investigate the causal relationship of buses during system disturbance. The IEEE 39-bus system and IEEE 118-bus system are employed to validate and evaluate the proposed approach.« less

ACCELERATORS: Preliminary application of turn-by-turn data analysis to the SSRF storage ring

NASA Astrophysics Data System (ADS)

Chen, Jian-Hui; Zhao, Zhen-Tang

2009-07-01

There is growing interest in utilizing the beam position monitor turn-by-turn (TBT) data to debug accelerators. TBT data can be used to determine the linear optics, coupled optics and nonlinear behaviors of the storage ring lattice. This is not only a useful complement to other methods of determining the linear optics such as LOCO, but also provides a possibility to uncover more hidden phenomena. In this paper, a preliminary application of a β function measurement to the SSRF storage ring is presented.

Uncovering the Hidden Structure of Platoons: Formal and Emergent Leaders’ Perceptions of Organizational Networks

DTIC Science & Technology

2008-12-01

perceptions of formal and emergent leaders differ from those of non-leaders, and if so, how. We approach this topic through the lens of social network...analysis. 1.1 Social Networks The term “ social network” refers to a set of actors who are connected by a set of ties. Actors, often referred to as...the structure of any social system can be defined as a set of relations between all pairs of individuals who are members of the network (Krackhardt

Results of a Formal Methods Demonstration Project

NASA Technical Reports Server (NTRS)

Kelly, J.; Covington, R.; Hamilton, D.

1994-01-01

This paper describes the results of a cooperative study conducted by a team of researchers in formal methods at three NASA Centers to demonstrate FM techniques and to tailor them to critical NASA software systems. This pilot project applied FM to an existing critical software subsystem, the Shuttle's Jet Select subsystem (Phase I of an ongoing study). The present study shows that FM can be used successfully to uncover hidden issues in a highly critical and mature Functional Subsystem Software Requirements (FSSR) specification which are very difficult to discover by traditional means.

Estimating Temporal Causal Interaction between Spike Trains with Permutation and Transfer Entropy

PubMed Central

Li, Zhaohui; Li, Xiaoli

2013-01-01

Estimating the causal interaction between neurons is very important for better understanding the functional connectivity in neuronal networks. We propose a method called normalized permutation transfer entropy (NPTE) to evaluate the temporal causal interaction between spike trains, which quantifies the fraction of ordinal information in a neuron that has presented in another one. The performance of this method is evaluated with the spike trains generated by an Izhikevich’s neuronal model. Results show that the NPTE method can effectively estimate the causal interaction between two neurons without influence of data length. Considering both the precision of time delay estimated and the robustness of information flow estimated against neuronal firing rate, the NPTE method is superior to other information theoretic method including normalized transfer entropy, symbolic transfer entropy and permutation conditional mutual information. To test the performance of NPTE on analyzing simulated biophysically realistic synapses, an Izhikevich’s cortical network that based on the neuronal model is employed. It is found that the NPTE method is able to characterize mutual interactions and identify spurious causality in a network of three neurons exactly. We conclude that the proposed method can obtain more reliable comparison of interactions between different pairs of neurons and is a promising tool to uncover more details on the neural coding. PMID:23940662

Discovering Coherent Structures Using Local Causal States

NASA Astrophysics Data System (ADS)

Rupe, Adam; Crutchfield, James P.; Kashinath, Karthik; Prabhat, Mr.

2017-11-01

Coherent structures were introduced in the study of fluid dynamics and were initially defined as regions characterized by high levels of coherent vorticity, i.e. regions where instantaneously space and phase correlated vorticity are high. In a more general spatiotemporal setting, coherent structures can be seen as localized broken symmetries which persist in time. Building off the computational mechanics framework, which integrates tools from computation and information theory to capture pattern and structure in nonlinear dynamical systems, we introduce a theory of coherent structures, in the more general sense. Central to computational mechanics is the causal equivalence relation, and a local spatiotemporal generalization of it is used to construct the local causal states, which are utilized to uncover a system's spatiotemporal symmetries. Coherent structures are then identified as persistent, localized deviations from these symmetries. We illustrate how novel patterns and structures can be discovered in cellular automata and outline the path from them to laminar, transitional and turbulent flows. Funded by Intel through the Big Data Center at LBNL and the IPCC at UC Davis.

Bibliographic Resources for the Historian of Astronomy

NASA Astrophysics Data System (ADS)

Corbin, B. G.

1999-12-01

Many large library collections now have online bibliographic catalogs on the web. These provide many hidden resources for the historian of astronomy. Special searching techniques will allow the historian to scan bibliographic records of hundreds of entries relating to biographies of astronomers, collected works of astronomers, ancient and medieval astronomy and many other historical subjects. Abstract databases such as the Astrophysics Data System and ARIBIB are also adding much historical bibliographic information. ARIBIB will eventually contain scanned images of the Astronomischer Jahresbericht containing bibliographic entries for all literature of astronomy from 1899 to 1968 and Astronomy and Astrophysics Abstracts from 1969 to present. Commercial services such as UnCover and FirstSearch provide a means of reaching bibliographic entries for journal and book literature in the history of astronomy which were not easily located in the past. A broad overview of these collections and services will be given, and searching techniques for finding ``hidden" bibliographic data will be presented. Web page addresses will be given for all sources covered.

Hidden phase in a two-dimensional Sn layer stabilized by modulation hole doping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ming, Fangfei; Mulugeta Amare, Daniel; Tu, Weisong

Semiconductor surfaces and ultrathin interfaces exhibit an interesting variety of two-dimensional quantum matter phases, such as charge density waves, spin density waves and superconducting condensates. Yet, the electronic properties of these broken symmetry phases are extremely difficult to control due to the inherent difficulty of doping a strictly two-dimensional material without introducing chemical disorder. Here we successfully exploit a modulation doping scheme to uncover, in conjunction with a scanning tunnelling microscope tip-assist, a hidden equilibrium phase in a hole-doped bilayer of Sn on Si(111). This new phase is intrinsically phase separated into insulating domains with polar and nonpolar symmetries. Itsmore » formation involves a spontaneous symmetry breaking process that appears to be electronically driven, notwithstanding the lack of metallicity in this system. This modulation doping approach allows access to novel phases of matter, promising new avenues for exploring competing quantum matter phases on a silicon platform.« less

Implications for research and practice of the biographic approach for storytelling.

PubMed

Ewens, Beverley; Hendricks, Joyce; Sundin, Deb

2017-01-23

Background Intensive care unit survivors face many physical and psychological difficulties during their recovery following discharge from hospital. These difficulties can significantly affect their quality of life. Healthcare providers and survivors' families often do not understand what recovery means in this population, which may affect the support provided. Aim To consider the potential of the biographical method in helping to create stories that illustrate recovery in intensive care survivors and other populations. Discussion This paper identifies how the biographical approach has provided survivors with a way to uncover the hidden parts of their lives through diaries and interviews, and reveal the hidden stories of intensive care survivorship and recovery. Conclusion The application of the biographical method enabled stories to be created that identified the disruption survivors encounter as they struggle to appear recovered. Implications for practice The biographical method can illuminate experiences uncaptured by other methods. This insight into recovery journeys can help healthcare practitioners and family members to understand and recognise the need for support during recovery.

Factors Affecting Infants’ Manual Search for Occluded Objects and the Genesis of Object Permanence

PubMed Central

Moore, M. Keith; Meltzoff, Andrew N.

2009-01-01

Two experiments systematically examined factors that influence infants’ manual search for hidden objects (N = 96). Experiment 1 used a new procedure to assess infants’ search for partially versus totally occluded objects. Results showed that 8.75-month-old infants solved partial occlusions by removing the occluder and uncovering the object, but these same infants failed to use this skill on total occlusions. Experiment 2 used sound-producing objects to provide a perceptual clue to the objects’ hidden location. Sound clues significantly increased the success rate on total occlusions for 10-month-olds, but not for 8.75-month-olds. An identity development account is offered for why infants succeed on partial occlusions earlier than total occlusions and why sound helps only the older infants. We propose a mechanism for how infants use object identity as a basis for developing a notion of permanence. Implications are drawn for understanding the dissociation between looking-time and search assessments of object permanence. PMID:18036668

Factors affecting infants' manual search for occluded objects and the genesis of object permanence.

PubMed

Moore, M Keith; Meltzoff, Andrew N

2008-04-01

Two experiments systematically examined factors that influence infants' manual search for hidden objects (N=96). Experiment 1 used a new procedure to assess infants' search for partially versus totally occluded objects. Results showed that 8.75-month-old infants solved partial occlusions by removing the occluder and uncovering the object, but these same infants failed to use this skill on total occlusions. Experiment 2 used sound-producing objects to provide a perceptual clue to the objects' hidden location. Sound clues significantly increased the success rate on total occlusions for 10-month-olds, but not for 8.75-month-olds. An identity development account is offered for why infants succeed on partial occlusions earlier than total occlusions and why sound helps only the older infants. We propose a mechanism for how infants use object identity as a basis for developing a notion of permanence. Implications are drawn for understanding the dissociation between looking time and search assessments of object permanence.

Hidden phase in a two-dimensional Sn layer stabilized by modulation hole doping

DOE PAGES

Ming, Fangfei; Mulugeta Amare, Daniel; Tu, Weisong; ...

2017-03-07

Semiconductor surfaces and ultrathin interfaces exhibit an interesting variety of two-dimensional quantum matter phases, such as charge density waves, spin density waves and superconducting condensates. Yet, the electronic properties of these broken symmetry phases are extremely difficult to control due to the inherent difficulty of doping a strictly two-dimensional material without introducing chemical disorder. Here we successfully exploit a modulation doping scheme to uncover, in conjunction with a scanning tunnelling microscope tip-assist, a hidden equilibrium phase in a hole-doped bilayer of Sn on Si(111). This new phase is intrinsically phase separated into insulating domains with polar and nonpolar symmetries. Itsmore » formation involves a spontaneous symmetry breaking process that appears to be electronically driven, notwithstanding the lack of metallicity in this system. This modulation doping approach allows access to novel phases of matter, promising new avenues for exploring competing quantum matter phases on a silicon platform.« less

The missing history of Bohm's hidden variables theory: The Ninth Symposium of the Colston Research Society, Bristol, 1957

NASA Astrophysics Data System (ADS)

Kožnjak, Boris

2018-05-01

In this paper, I analyze the historical context, scientific and philosophical content, and the implications of the thus far historically largely neglected Ninth Symposium of the Colston Research Society held in Bristol at the beginning of April 1957, the first major international event after World War II gathering eminent physicists and philosophers to discuss the foundational questions of quantum mechanics, in respect to the early reception of the causal quantum theory program mapped and defended by David Bohm during the five years preceding the Symposium. As will be demonstrated, contrary to the almost unanimously negative and even hostile reception of Bohm's ideas on hidden variables in the early 1950s, in the close aftermath of the 1957 Colston Research Symposium Bohm's ideas received a more open-minded and ideologically relaxed critical rehabilitation, in which the Symposium itself played a vital and essential part.

Identification of Variant-Specific Functions of PIK3CA by Rapid Phenotyping of Rare Mutations | Office of Cancer Genomics

Cancer.gov

Large-scale sequencing efforts are uncovering the complexity of cancer genomes, which are composed of causal "driver" mutations that promote tumor progression along with many more pathologically neutral "passenger" events. The majority of mutations, both in known cancer drivers and uncharacterized genes, are generally of low occurrence, highlighting the need to functionally annotate the long tail of infrequent mutations present in heterogeneous cancers.

Reading Hidden Messages Through Deciphered Manual Alphabets on Classic Artwork

NASA Astrophysics Data System (ADS)

Castronovo, Joseph Anthony, Jr.

1998-10-01

Decipherment is the tool used to uncover several types of hand signs that played vital roles in the creation of hidden messages in classic artwork. A 3,100 B.C. bas-relief of The 'Kaph' Telescope, formerly named The Narmer Palette, and Michaelangelo Buonarrotte's Battle of Cascina of 1506 were two key works of art that show certain similarities even though separated by 4,500 years. It is evident that Renaissance humanists provided artists with certain knowledge of the ancients. Results of incorporating a number of minor works of art showed that the competence of ancient Egyptians, Cretans and Australian Aboriginals, to name a few, as astronomers, was underestimated. Some deciphered Indus seals attested to a global understanding of the universe, with Gemini and the star of Thuban at the center of their attention. Certain forms of secrecy had to be undertaken for various reasons throughout the millennia. Three examples are: (1) In Italy, to keep controversial and truthful teachings discreet and hidden, artists embedded them in artwork long before the plight of Galileo Galilei and his discoveries. (2) Among Jewish Kabbalists, a well-known design was obscured in The Arnolfini Wedding painting for fear it would be lost due to persecution. (3) Michaelangelo Buonarrotte indicated several meanings through the hands of The Statue of Moses. They were overlooked by several societies, including the gesticulating culture of Italy, because they oppressed the value of signed languages. Spatial decipherment may testify to a need for the restoration of a spatial writing system for expanded linguistic accessibility. A 21st century model community for sign language residents and employees will benefit visual learners, particularly visual artists and non-phonetic decipherers, to better uncover, understand and perhaps use ancient hand forms to restore ancient knowledge. Moreover, the National Association of Teaching English (NATE) has recently endorsed the addition of two skills, viewing and visual representing, to the traditional list of reading, writing, speaking and listening. Students will master these two new skills far more effectively when they are exposed to such a signing community.

Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

PubMed

Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

2018-06-05

Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

Uncovering the inertia of dislocation motion and negative mechanical response in crystals.

PubMed

Tang, Yizhe

2018-01-09

Dislocations are linear defects in crystals and their motion controls crystals' mechanical behavior. The dissipative nature of dislocation propagation is generally accepted although the specific mechanisms are still not fully understood. The inertia, which is undoubtedly the nature of motion for particles with mass, seems much less convincing for configuration propagation. We utilize atomistic simulations in conditions that minimize dissipative effects to enable uncovering of the hidden nature of dislocation motion, in three typical model metals Mg, Cu and Ta. We find that, with less/no dissipation, dislocation motion is under-damped and explicitly inertial at both low and high velocities. The inertia of dislocation motion is intrinsic, and more fundamental than the dissipative nature. The inertia originates from the kinetic energy imparted from strain energy and stored in the moving core. Peculiar negative mechanical response associated with the inertia is also discovered. These findings shed light on the fundamental nature of dislocation motion, reveal the underlying physics, and provide a new physical explanation for phenomena relevant to high-velocity dislocations.

Dynamics and causalities of atmospheric and oceanic data identified by complex networks and Granger causality analysis

NASA Astrophysics Data System (ADS)

Charakopoulos, A. K.; Katsouli, G. A.; Karakasidis, T. E.

2018-04-01

Understanding the underlying processes and extracting detailed characteristics of spatiotemporal dynamics of ocean and atmosphere as well as their interaction is of significant interest and has not been well thoroughly established. The purpose of this study was to examine the performance of two main additional methodologies for the identification of spatiotemporal underlying dynamic characteristics and patterns among atmospheric and oceanic variables from Seawatch buoys from Aegean and Ionian Sea, provided by the Hellenic Center for Marine Research (HCMR). The first approach involves the estimation of cross correlation analysis in an attempt to investigate time-lagged relationships, and further in order to identify the direction of interactions between the variables we performed the Granger causality method. According to the second approach the time series are converted into complex networks and then the main topological network properties such as degree distribution, average path length, diameter, modularity and clustering coefficient are evaluated. Our results show that the proposed analysis of complex network analysis of time series can lead to the extraction of hidden spatiotemporal characteristics. Also our findings indicate high level of positive and negative correlations and causalities among variables, both from the same buoy and also between buoys from different stations, which cannot be determined from the use of simple statistical measures.

Cultural boundary surfing in mental health nursing: a creative narration.

PubMed

Kidd, Jacquie

2010-01-01

In the mental health context, nurses navigate multifaceted boundaries every day in an effort to develop and maintain the therapeutic relationship; an endeavour that is breathtaking in its complexity. In this paper, I adopt an unconventional form of writing to explore the individual nature of cultural boundaries, and uncover hidden messages that impact on our efforts to build connections across cultures and ethnicities in mental health settings. Presented as a play, the conversation between protagonists explores cultural competence alongside the notion of 'discovery', and the potential of the Tidal Model to provide a vehicle for successful cultural boundary surfing.

Uncovering the Hidden Molecular Signatures of Breast Cancer

DTIC Science & Technology

2011-05-01

0389$&0>!1&! :79).3$$7! ,3D&! 0/8&! )56/%83:)/5! %&=3%*)5=! 93:)&5:! .$)5).3$! 3::%)4(:&0! )5.$(*)5=! :(8/%! =%3*&>! 0:3=&>! HFI ! 0:3:(0>! N&%A! 0:3:(0...5! :,&! 93%:).($3%! ’(&0:)/5! 4&)5=! 302&*! /6! :,&! 93:)&5:! *3:30&:;! P/%! &G389$&>! =)D&5! 3! :%350.%)9:)/53$! 0)=53:(%&! /6! HFI ! 3.:)D3:)/5! B:,3...0>! :,&!=&5&!0&:!./%%&09/5*)5=!:/! :%350.%)9:0! :,3:!3%&!*)66&%&5:)3$$7!&G9%&00&*! 1,&5! HFI ! )0! /D&%R&G9%&00&*E>! 93:)&5:0! 3%&! /%*&%&*! 3

DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework

PubMed Central

Richmond, Rebecca C.; Ward, Mary E.; Fraser, Abigail; Lyttleton, Oliver; McArdle, Wendy L.; Ring, Susan M.; Gaunt, Tom R.; Lawlor, Debbie A.; Davey Smith, George; Relton, Caroline L.

2016-01-01

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. PMID:26861784

New insights on emergence from the perspective of weak values and dynamical non-locality

NASA Astrophysics Data System (ADS)

Tollaksen, Jeff

2014-04-01

In this article, we will examine new fundamental aspects of "emergence" and "information" using novel approaches to quantum mechanics which originated from the group around Aharonov. The two-state vector formalism provides a complete description of pre- and post-selected quantum systems and has uncovered a host of new quantum phenomena which were previously hidden. The most important feature is that any weak coupling to a pre- and post-selected system is effectively a coupling to a "weak value" which is given by a simple expression depending on the two-state vector. In particular, weak values, are the outcomes of so called "weak measurements" which have recently become a very powerful tool for ultra-sensitive measurements. Using weak values, we will show how to separate a particle from its properties, not unlike the Cheshire cat story: "Well! I've often seen a cat without a grin," thought Alice; "but a grin without a cat! It's the most curious thing I ever saw in all my life!" Next, we address the question whether the physics on different scales "emerges" from quantum mechanics or whether the laws of physics at those scales are fundamental. We show that the classical limit of quantum mechanics is a far more complicated issue; it is in fact dramatically more involved and it requires a complete revision of all our intuitions. The revised intuitions can then serve as a guide to finding novel quantum effects. Next we show that novel experimental aspects of contextuality can be demonstrated with weak measurements and these suggest new restrictions on hidden variable approaches. Next we emphasize that the most important implication of the Aharonov-Bohm effect is the existence of non-local interactions which do not violate causality. Finally, we review some generalizations of quantum mechanics and their implications for "emergence" and "information." First, we review an alternative approach to quantum evolution in which each moment of time is viewed as a new "universe" and time evolution is given by correlations between different moments. Next, we present a new solution to the measurement problem involving future boundary conditions placed on the universe as a whole. Finally, we introduce another fundamental approach to quantum evolution which allows for tremendous richness in the types of allowable Hamiltonians.

Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

PubMed Central

Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K.; Thomas, Venetta; Ambrosone, Christine B.; Bandera, Elisa V.; Berndt, Sonja I.; Bernstein, Leslie; Blot, William J.; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J.; Cheng, Iona; Chu, Lisa; Deming, Sandra L.; Driver, W. Ryan; Goodman, Phyllis; Hayes, Richard B.; Hennis, Anselm J. M.; Hsing, Ann W.; Hu, Jennifer J.; Ingles, Sue A.; John, Esther M.; Kittles, Rick A.; Kolb, Suzanne; Leske, M. Cristina; Monroe, Kristine R.; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F.; Rodriguez-Gil, Jorge L.; Rybicki, Ben A.; Schumacher, Fredrick; Stanford, Janet L.; Signorello, Lisa B.; Strom, Sara S.; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S.; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G.; Stram, Alexander H.; Kolonel, Laurence N.; Marchand, Loïc Le; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

2015-01-01

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious. PMID:26125186

Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults.

PubMed

Chen, Fang; He, Jing; Zhang, Jianqi; Chen, Gary K; Thomas, Venetta; Ambrosone, Christine B; Bandera, Elisa V; Berndt, Sonja I; Bernstein, Leslie; Blot, William J; Cai, Qiuyin; Carpten, John; Casey, Graham; Chanock, Stephen J; Cheng, Iona; Chu, Lisa; Deming, Sandra L; Driver, W Ryan; Goodman, Phyllis; Hayes, Richard B; Hennis, Anselm J M; Hsing, Ann W; Hu, Jennifer J; Ingles, Sue A; John, Esther M; Kittles, Rick A; Kolb, Suzanne; Leske, M Cristina; Millikan, Robert C; Monroe, Kristine R; Murphy, Adam; Nemesure, Barbara; Neslund-Dudas, Christine; Nyante, Sarah; Ostrander, Elaine A; Press, Michael F; Rodriguez-Gil, Jorge L; Rybicki, Ben A; Schumacher, Fredrick; Stanford, Janet L; Signorello, Lisa B; Strom, Sara S; Stevens, Victoria; Van Den Berg, David; Wang, Zhaoming; Witte, John S; Wu, Suh-Yuh; Yamamura, Yuko; Zheng, Wei; Ziegler, Regina G; Stram, Alexander H; Kolonel, Laurence N; Le Marchand, Loïc; Henderson, Brian E; Haiman, Christopher A; Stram, Daniel O

2015-01-01

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large number of SNPs are used in the analysis; and (2) whether estimation of heritability may be biased, in real studies, by low levels of residual hidden relatedness. We addressed the first question in a semi-analytic fashion by directly simulating the distribution of the score statistic for a test of zero heritability with and without low levels of relatedness. The second question was addressed by a very careful comparison of the behavior of estimated heritability for both observed (self-reported) height and simulated phenotypes compared to imputation R2 as a function of the number of SNPs used in the analysis. These simulations help to address the important question about whether today's GWAS SNPs will remain useful for imputing causal variants that are discovered using very large sample sizes in future studies of height, or whether the causal variants themselves will need to be genotyped de novo in order to build a prediction model that ultimately captures a large fraction of the variability of height, and by implication other complex phenotypes. Our overall conclusions are that when study sizes are quite large (5,000 or so) the additive heritability estimate for height is not apparently biased upwards using the linear mixed model; however there is evidence in our simulation that a very large number of causal variants (many thousands) each with very small effect on phenotypic variance will need to be discovered to fill the gap between the heritability explained by known versus unknown causal variants. We conclude that today's GWAS data will remain useful in the future for causal variant prediction, but that finding the causal variants that need to be predicted may be extremely laborious.

Foundational perspectives on causality in large-scale brain networks

NASA Astrophysics Data System (ADS)

Mannino, Michael; Bressler, Steven L.

2015-12-01

A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical likelihood that a change in the activity of one neuronal population affects the activity in another. We argue that these measures access the inherently probabilistic nature of causal influences in the brain, and are thus better suited for large-scale brain network analysis than are DC-based measures. Our work is consistent with recent advances in the philosophical study of probabilistic causality, which originated from inherent conceptual problems with deterministic regularity theories. It also resonates with concepts of stochasticity that were involved in establishing modern physics. In summary, we argue that probabilistic causality is a conceptually appropriate foundation for describing neural causality in the brain.

Foundational perspectives on causality in large-scale brain networks.

PubMed

Mannino, Michael; Bressler, Steven L

2015-12-01

A profusion of recent work in cognitive neuroscience has been concerned with the endeavor to uncover causal influences in large-scale brain networks. However, despite the fact that many papers give a nod to the important theoretical challenges posed by the concept of causality, this explosion of research has generally not been accompanied by a rigorous conceptual analysis of the nature of causality in the brain. This review provides both a descriptive and prescriptive account of the nature of causality as found within and between large-scale brain networks. In short, it seeks to clarify the concept of causality in large-scale brain networks both philosophically and scientifically. This is accomplished by briefly reviewing the rich philosophical history of work on causality, especially focusing on contributions by David Hume, Immanuel Kant, Bertrand Russell, and Christopher Hitchcock. We go on to discuss the impact that various interpretations of modern physics have had on our understanding of causality. Throughout all this, a central focus is the distinction between theories of deterministic causality (DC), whereby causes uniquely determine their effects, and probabilistic causality (PC), whereby causes change the probability of occurrence of their effects. We argue that, given the topological complexity of its large-scale connectivity, the brain should be considered as a complex system and its causal influences treated as probabilistic in nature. We conclude that PC is well suited for explaining causality in the brain for three reasons: (1) brain causality is often mutual; (2) connectional convergence dictates that only rarely is the activity of one neuronal population uniquely determined by another one; and (3) the causal influences exerted between neuronal populations may not have observable effects. A number of different techniques are currently available to characterize causal influence in the brain. Typically, these techniques quantify the statistical likelihood that a change in the activity of one neuronal population affects the activity in another. We argue that these measures access the inherently probabilistic nature of causal influences in the brain, and are thus better suited for large-scale brain network analysis than are DC-based measures. Our work is consistent with recent advances in the philosophical study of probabilistic causality, which originated from inherent conceptual problems with deterministic regularity theories. It also resonates with concepts of stochasticity that were involved in establishing modern physics. In summary, we argue that probabilistic causality is a conceptually appropriate foundation for describing neural causality in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimation of effective connectivity using multi-layer perceptron artificial neural network.

PubMed

Talebi, Nasibeh; Nasrabadi, Ali Motie; Mohammad-Rezazadeh, Iman

2018-02-01

Studies on interactions between brain regions estimate effective connectivity, (usually) based on the causality inferences made on the basis of temporal precedence. In this study, the causal relationship is modeled by a multi-layer perceptron feed-forward artificial neural network, because of the ANN's ability to generate appropriate input-output mapping and to learn from training examples without the need of detailed knowledge of the underlying system. At any time instant, the past samples of data are placed in the network input, and the subsequent values are predicted at its output. To estimate the strength of interactions, the measure of " Causality coefficient " is defined based on the network structure, the connecting weights and the parameters of hidden layer activation function. Simulation analysis demonstrates that the method, called "CREANN" (Causal Relationship Estimation by Artificial Neural Network), can estimate time-invariant and time-varying effective connectivity in terms of MVAR coefficients. The method shows robustness with respect to noise level of data. Furthermore, the estimations are not significantly influenced by the model order (considered time-lag), and the different initial conditions (initial random weights and parameters of the network). CREANN is also applied to EEG data collected during a memory recognition task. The results implicate that it can show changes in the information flow between brain regions, involving in the episodic memory retrieval process. These convincing results emphasize that CREANN can be used as an appropriate method to estimate the causal relationship among brain signals.

Out of the white hole: a holographic origin for the Big Bang

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pourhasan, Razieh; Afshordi, Niayesh; Mann, Robert B., E-mail: rpourhasan@perimeterinstitute.ca, E-mail: nafshordi@pitp.ca, E-mail: rbmann@uwaterloo.ca

While most of the singularities of General Relativity are expected to be safely hidden behind event horizons by the cosmic censorship conjecture, we happen to live in the causal future of the classical Big Bang singularity, whose resolution constitutes the active field of early universe cosmology. Could the Big Bang be also hidden behind a causal horizon, making us immune to the decadent impacts of a naked singularity? We describe a braneworld description of cosmology with both 4d induced and 5D bulk gravity (otherwise known as Dvali-Gabadadze-Porati, or DGP model), which exhibits this feature: the universe emerges as a sphericalmore » 3-brane out of the formation of a 5D Schwarzschild black hole. In particular, we show that a pressure singularity of the holographic fluid, discovered earlier, happens inside the white hole horizon, and thus need not be real or imply any pathology. Furthermore, we outline a novel mechanism through which any thermal atmosphere for the brane, with comoving temperature of ∼20% of the 5D Planck mass can induce scale-invariant primordial curvature perturbations on the brane, circumventing the need for a separate process (such as cosmic inflation) to explain current cosmological observations. Finally, we note that 5D space-time is asymptotically flat, and thus potentially allows an S-matrix or (after minor modifications) an AdS/CFT description of the cosmological Big Bang.« less

Bohr, Heisenberg and the divergent views of complementarity

NASA Astrophysics Data System (ADS)

Camilleri, Kristian

The fractious discussions between Bohr and Heisenberg in Copenhagen in 1927 have been the subject of much historical scholarship. However, little attention has been given to Heisenberg's understanding of the notion of complementary space-time and causal descriptions, which was presented for the first time in Bohr's lecture at the 1927 Como conference. In this paper, I argue that Heisenberg's own interpretation of this notion differed substantially from Bohr's. Whereas Bohr had intended this form of complementarity to entail a choice between a space-time description of the electron in an atom, and defining the energy of a stationary state, Heisenberg interpreted the 'causal' description in terms of ψ -function in configuration space. In disentangling the two views of complementarity, this paper sheds new light on the hidden philosophical disagreements between the proponents of these two founders of the so-called 'Copenhagen interpretation' of quantum mechanics.

The growth crisis--and how to escape it.

PubMed

Slywotzky, Adrian J; Wise, Richard

2002-07-01

At a time when companies are poised to seize the growth opportunities of a rebounding economy, many of them, whether they know it or not, face a growth crisis. Even during the boom years of the past decade, only a small fraction of companies enjoyed consistent double-digit revenue growth. And those that did often achieved it through short-term measures--such as mergers and inflated price increases--that don't provide the foundation for growth over the long term. But there is a way out of this predicament. The authors claim that companies can achieve sustained growth by leveraging their "hidden assets," a wide array of underused, intangible capabilities and advantages that most established companies already hold. To date, much of the research on intangible assets has centered on intellectual property and brand recognition. But in this article, the authors uncover a host of other assets that can help spark growth. They identify four major categories of hidden assets: customer relationships, strategic real estate, networks, and information. And they illustrate each with an example of a company that has creatively used its hidden assets to produce new sources of revenue. Executives have spent years learning to create growth using products, facilities, and working capital. But they should really focus on mobilizing their hidden assets to serve their customers' higher-order needs--in other words, create offerings that make customers' lives easier, better, or less expensive. Making that shift in mind-set isn't easy, admit the authors, but companies that do it may not only create meaningful new value for their customers but also produce double-digit revenue and earnings growth for investors.

The Challenge of Stress-Related Non-Communicable Diseases.

PubMed

Fricchione, Gregory L

2018-06-15

The greatest challenge facing medicine today involves the so-called non-communicable diseases (NCDs). This is true regardless of whether one's location is considered high-income, middle-income, or low-income. Basic research at all "OMICs" system levels will be significant in uncovering causal links that create NCD vulnerabilities in mind, brain, body, and society. Therefore, meeting this 21st century challenge by improving NCD management and prevention around the world will rely on advancement in this type of basic research.

A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3

PubMed Central

Yu, Eun Young; Wang, Feng; Lei, Ming; Lue, Neal F

2008-01-01

Ever shorter telomeres 3 (Est3) is an essential telomerase regulatory subunit thought to be unique to budding yeasts. Here we use multiple sequence alignment and hidden Markov model–hidden Markov model (HMM-HMM) comparison to uncover potential similarities between Est3 and the mammalian telomeric protein Tpp1. Analysis of site-specific mutants of Candida albicans Est3 revealed functional distinctions between residues that are conserved between Est3 and Tpp1 and those that are unique to Est3. Although both types of residues are important for telomere maintenance in vivo, only the former contributes to telomerase activity in vitro and facilitates the association of Est3 with telomerase core components. Consistent with a function in protein-protein interaction, the residues common to Est3 and Tpp1 map to one face of an OB-fold model structure, away from the canonical nucleic acid binding surface. We propose that Est3 and the OB-fold domain of Tpp1 mediate a conserved function in telomerase regulation. PMID:19172753

Childhood temperament: passive gene-environment correlation, gene-environment interaction, and the hidden importance of the family environment.

PubMed

Lemery-Chalfant, Kathryn; Kao, Karen; Swann, Gregory; Goldsmith, H Hill

2013-02-01

Biological parents pass on genotypes to their children, as well as provide home environments that correlate with their genotypes; thus, the association between the home environment and children's temperament can be genetically (i.e., passive gene-environment correlation) or environmentally mediated. Furthermore, family environments may suppress or facilitate the heritability of children's temperament (i.e., gene-environment interaction). The sample comprised 807 twin pairs (mean age = 7.93 years) from the longitudinal Wisconsin Twin Project. Important passive gene-environment correlations emerged, such that home environments were less chaotic for children with high effortful control, and this association was genetically mediated. Children with high extraversion/surgency experienced more chaotic home environments, and this correlation was also genetically mediated. In addition, heritability of children's temperament was moderated by home environments, such that effortful control and extraversion/surgency were more heritable in chaotic homes, and negative affectivity was more heritable under crowded or unsafe home conditions. Modeling multiple types of gene-environment interplay uncovered the complex role of genetic factors and the hidden importance of the family environment for children's temperament and development more generally.

"Dark matter" worlds of unstable RNA and protein.

PubMed

Baboo, Sabyasachi; Cook, Peter R

2014-01-01

Astrophysicists use the term "dark matter" to describe the majority of the matter and/or energy in the universe that is hidden from view, and biologists now apply it to the new families of RNA they are uncovering. We review evidence for an analogous hidden world containing peptides. The critical experiments involved pulse-labeling human cells with tagged amino acids for periods as short as five seconds. Results are extraordinary in two respects: both nucleus and cytoplasm become labeled, and most signals disappear with a half-life of less than one minute. Just as the synthesis of each mature mRNA is regulated by the abortive production of hundreds of shorter transcripts that are quickly degraded, it seems that the synthesis of each full-length protein in the stable proteome is regulated by an apparently wasteful production and degradation of shorter peptides. Some of the nuclear synthesis is probably a byproduct of nuclear ribosomes proofreading newly-made RNA for inappropriately-placed termination codons (a process that triggers "nonsense-mediated decay"). We speculate that some "dark-matter" peptides will play other important roles in the cell.

“Dark matter” worlds of unstable RNA and protein

PubMed Central

Baboo, Sabyasachi; Cook, Peter R

2014-01-01

Astrophysicists use the term “dark matter” to describe the majority of the matter and/or energy in the universe that is hidden from view, and biologists now apply it to the new families of RNA they are uncovering. We review evidence for an analogous hidden world containing peptides. The critical experiments involved pulse-labeling human cells with tagged amino acids for periods as short as five seconds. Results are extraordinary in two respects: both nucleus and cytoplasm become labeled, and most signals disappear with a half-life of less than one minute. Just as the synthesis of each mature mRNA is regulated by the abortive production of hundreds of shorter transcripts that are quickly degraded, it seems that the synthesis of each full-length protein in the stable proteome is regulated by an apparently wasteful production and degradation of shorter peptides. Some of the nuclear synthesis is probably a byproduct of nuclear ribosomes proofreading newly-made RNA for inappropriately-placed termination codons (a process that triggers “nonsense-mediated decay”). We speculate that some “dark-matter” peptides will play other important roles in the cell. PMID:25482115

Quantitative EEG analysis using error reduction ratio-causality test; validation on simulated and real EEG data.

PubMed

Sarrigiannis, Ptolemaios G; Zhao, Yifan; Wei, Hua-Liang; Billings, Stephen A; Fotheringham, Jayne; Hadjivassiliou, Marios

2014-01-01

To introduce a new method of quantitative EEG analysis in the time domain, the error reduction ratio (ERR)-causality test. To compare performance against cross-correlation and coherence with phase measures. A simulation example was used as a gold standard to assess the performance of ERR-causality, against cross-correlation and coherence. The methods were then applied to real EEG data. Analysis of both simulated and real EEG data demonstrates that ERR-causality successfully detects dynamically evolving changes between two signals, with very high time resolution, dependent on the sampling rate of the data. Our method can properly detect both linear and non-linear effects, encountered during analysis of focal and generalised seizures. We introduce a new quantitative EEG method of analysis. It detects real time levels of synchronisation in the linear and non-linear domains. It computes directionality of information flow with corresponding time lags. This novel dynamic real time EEG signal analysis unveils hidden neural network interactions with a very high time resolution. These interactions cannot be adequately resolved by the traditional methods of coherence and cross-correlation, which provide limited results in the presence of non-linear effects and lack fidelity for changes appearing over small periods of time. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Enactive account of pretend play and its application to therapy

PubMed Central

Rucinska, Zuzanna; Reijmers, Ellen

2015-01-01

This paper informs therapeutic practices that use play, by providing a non-standard philosophical account of pretense: the enactive account of pretend play (EAPP). The EAPP holds that pretend play activity need not invoke mental representational mechanisms; instead, it focuses on interaction and the role of affordances in shaping pretend play activity. One advantage of this re-characterization of pretense is that it may help us better understand the role of shared meanings and interacting in systemic therapies, which use playing to enhance dialog in therapy rather than to uncover hidden meanings. We conclude with bringing together findings from therapeutic practice and philosophical considerations. PMID:25784884

Lesbian health and the assumption of heterosexuality: an organizational perspective.

PubMed

Daley, Andrea

2003-01-01

This study used a qualitative research design to explore hospital policies and practices and the assumption of female heterosexuality. The assumption of heterosexuality is a product of discursive practices that normalize heterosexuality and individualize lesbian sexual identities. Literature indicates that the assumption of female heterosexuality is implicated in both the invisibility and marked visibility of lesbians as service users. This research adds to existing literature by shifting the focus of study from individual to organizational practices and, in so doing, seeks to uncover hidden truths, explore the functional power of language, and allow for the discovery of what we know and--equally as important--how we know.

Fingerprint image enhancement by differential hysteresis processing.

PubMed

Blotta, Eduardo; Moler, Emilce

2004-05-10

A new method to enhance defective fingerprints images through image digital processing tools is presented in this work. When the fingerprints have been taken without any care, blurred and in some cases mostly illegible, as in the case presented here, their classification and comparison becomes nearly impossible. A combination of spatial domain filters, including a technique called differential hysteresis processing (DHP), is applied to improve these kind of images. This set of filtering methods proved to be satisfactory in a wide range of cases by uncovering hidden details that helped to identify persons. Dactyloscopy experts from Policia Federal Argentina and the EAAF have validated these results.

Uncovering Information Hidden in Web Archives: Glimpse at Web Analysis Building on Data Warehouses; Towards Continuous Web Archiving: First Results and an Agenda for the Future; The Open Video Digital Library; After Migration to an Electronic Journal Collection: Impact on Faculty and Doctoral Students; Who Is Reading On-Line Education Journals? Why? And What Are They Reading?; Report on eLibrary@UBC4: Research, Collaboration and the Digital Library - Visions for 2010.

ERIC Educational Resources Information Center

Rauber, Andreas; Bruckner, Robert M.; Aschenbrenner, Andreas; Witvoet, Oliver; Kaiser, Max; Masanes, Julien; Marchionini, Gary; Geisler, Gary; King, Donald W.; Montgomery, Carol Hansen; Rudner, Lawrence M.; Gellmann, Jennifer S.; Miller-Whitehead, Marie; Iverson, Lee

2002-01-01

These six articles discuss Web archives and Web analysis building on data warehouses; international efforts at continuous Web archiving; the Open Video Digital Library; electronic journal collections in academic libraries; online education journals; and an electronic library symposium at the University of British Columbia. (LRW)

On the zigzagging causality EPR model: Answer to Vigier and coworkers and to Sutherland

NASA Astrophysics Data System (ADS)

Costa de Beauregard, O.

1987-08-01

The concept of “propagation in time” of Vigier and co-workers (V et al.) implies the idea of a supertime; it is thus alien to most Minkowskian pictures and certainly to mine. From this stems much of V et al.'s misunderstandings of my position. In steady motion of a classical fluid nobody thinks that “momentum conservation is violated,” or that “momentum is shot upstream without cause” because of the suction from the sinks! Similarly with momentum-energy in space-time and the acceptance of an advanced causality. As for the CT invariance of the Feynman propagator, the causality asymmetry it entails is factlike, not lawlike. The geometrical counterpart of the symmetry between prediction and retrodiction and between retarded and advanced waves, as expressed in the alternative expressions == for a transition amplitude between a preparation |A> and a measurement |B>, is CPT-invariant, not PT-invariant. These three expressions respectively illustrate the collapse, the retrocollapse, and the symmetric collapse-and-retrocollapse concepts. As for Sutherland's argument, what it “falsifies” is not my retrocausation concept but the hidden-variables assumption he has unwittingly made.

Zigzagging causality EPR model: answer to Vigier and coworkers and to Sutherland

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Beauregard, O.C.

1987-08-01

The concept of propagation in time of Vigier and co-workers (V et al.) implies the ideal of a supertime; it is thus alien to most Minkowskian pictures and certainly to the authors. From this stems much of V et al.'s misunderstandings of his position. In steady motion of a classical fluid nobody thinks that momentum conservation is violated, or that momentum is shot upstream without cause because of the suction from the sinks. Similarly with momentum-energy in spacetime and the acceptance of an advanced causality. As for the CT invariance of the Feynman propagator, the causality asymmetry it entails ismore » factlike, not lawlike. The geometrical counterpart of the symmetry between prediction and retrodiction and between retarded and advanced waves, as expressed in the alternative expressions = = for a transition amplitude between a preparation lt. slashA> and a measurement lt. slashB>, is CPT-invariant, not PT-invariant. These three expressions respectively illustrate the collapse, the retrocollapse, and the symmetric collapse-and-retrocollapse concepts. As for Sutherland's argument, what it falsifies is not the authors retrocausation concept but the hidden-variables assumption he has unwittingly made.« less

Backward transfer entropy: Informational measure for detecting hidden Markov models and its interpretations in thermodynamics, gambling and causality

PubMed Central

Ito, Sosuke

2016-01-01

The transfer entropy is a well-established measure of information flow, which quantifies directed influence between two stochastic time series and has been shown to be useful in a variety fields of science. Here we introduce the transfer entropy of the backward time series called the backward transfer entropy, and show that the backward transfer entropy quantifies how far it is from dynamics to a hidden Markov model. Furthermore, we discuss physical interpretations of the backward transfer entropy in completely different settings of thermodynamics for information processing and the gambling with side information. In both settings of thermodynamics and the gambling, the backward transfer entropy characterizes a possible loss of some benefit, where the conventional transfer entropy characterizes a possible benefit. Our result implies the deep connection between thermodynamics and the gambling in the presence of information flow, and that the backward transfer entropy would be useful as a novel measure of information flow in nonequilibrium thermodynamics, biochemical sciences, economics and statistics. PMID:27833120

Backward transfer entropy: Informational measure for detecting hidden Markov models and its interpretations in thermodynamics, gambling and causality

NASA Astrophysics Data System (ADS)

Ito, Sosuke

2016-11-01

The transfer entropy is a well-established measure of information flow, which quantifies directed influence between two stochastic time series and has been shown to be useful in a variety fields of science. Here we introduce the transfer entropy of the backward time series called the backward transfer entropy, and show that the backward transfer entropy quantifies how far it is from dynamics to a hidden Markov model. Furthermore, we discuss physical interpretations of the backward transfer entropy in completely different settings of thermodynamics for information processing and the gambling with side information. In both settings of thermodynamics and the gambling, the backward transfer entropy characterizes a possible loss of some benefit, where the conventional transfer entropy characterizes a possible benefit. Our result implies the deep connection between thermodynamics and the gambling in the presence of information flow, and that the backward transfer entropy would be useful as a novel measure of information flow in nonequilibrium thermodynamics, biochemical sciences, economics and statistics.

Leveraging lung tissue transcriptome to uncover candidate causal genes in COPD genetic associations.

PubMed

Lamontagne, Maxime; Bérubé, Jean-Christophe; Obeidat, Ma'en; Cho, Michael H; Hobbs, Brian D; Sakornsakolpat, Phuwanat; de Jong, Kim; Boezen, H Marike; Nickle, David; Hao, Ke; Timens, Wim; van den Berge, Maarten; Joubert, Philippe; Laviolette, Michel; Sin, Don D; Paré, Peter D; Bossé, Yohan

2018-05-15

Causal genes of chronic obstructive pulmonary disease (COPD) remain elusive. The current study aims at integrating genome-wide association studies (GWAS) and lung expression quantitative trait loci (eQTL) data to map COPD candidate causal genes and gain biological insights into the recently discovered COPD susceptibility loci. Two complementary genomic datasets on COPD were studied. First, the lung eQTL dataset which included whole-genome gene expression and genotyping data from 1038 individuals. Second, the largest COPD GWAS to date from the International COPD Genetics Consortium (ICGC) with 13 710 cases and 38 062 controls. Methods that integrated GWAS with eQTL signals including transcriptome-wide association study (TWAS), colocalization and Mendelian randomization-based (SMR) approaches were used to map causality genes, i.e. genes with the strongest evidence of being the functional effector at specific loci. These methods were applied at the genome-wide level and at COPD risk loci derived from the GWAS literature. Replication was performed using lung data from GTEx. We collated 129 non-overlapping risk loci for COPD from the GWAS literature. At the genome-wide scale, 12 new COPD candidate genes/loci were revealed and six replicated in GTEx including CAMK2A, DMPK, MYO15A, TNFRSF10A, BTN3A2 and TRBV30. In addition, we mapped candidate causal genes for 60 out of the 129 GWAS-nominated loci and 23 of them were replicated in GTEx. Mapping candidate causal genes in lung tissue represents an important contribution to the genetics of COPD, enriches our biological interpretation of GWAS findings, and brings us closer to clinical translation of genetic associations.

Hidden Genetic Variation in LCA9-Associated Congenital Blindness Explained by 5'UTR Mutations and Copy-Number Variations of NMNAT1.

PubMed

Coppieters, Frauke; Todeschini, Anne Laure; Fujimaki, Takuro; Baert, Annelot; De Bruyne, Marieke; Van Cauwenbergh, Caroline; Verdin, Hannah; Bauwens, Miriam; Ongenaert, Maté; Kondo, Mineo; Meire, Françoise; Murakami, Akira; Veitia, Reiner A; Leroy, Bart P; De Baere, Elfride

2015-12-01

Leber congenital amaurosis (LCA) is a severe autosomal-recessive retinal dystrophy leading to congenital blindness. A recently identified LCA gene is NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are coding variations, there is accumulating evidence for hidden noncoding defects or structural variations (SVs). The starting point of this study was an LCA9-associated consanguineous family in which no coding mutations were found in the LCA9 region. Exploring the untranslated regions of NMNAT1 revealed a novel homozygous 5'UTR variant, c.-70A>T. Moreover, an adjacent 5'UTR variant, c.-69C>T, was identified in a second consanguineous family displaying a similar phenotype. Both 5'UTR variants resulted in decreased NMNAT1 mRNA abundance in patients' lymphocytes, and caused decreased luciferase activity in human retinal pigment epithelial RPE-1 cells. Second, we unraveled pseudohomozygosity of a coding NMNAT1 mutation in two unrelated LCA patients by the identification of two distinct heterozygous partial NMNAT1 deletions. Molecular characterization of the breakpoint junctions revealed a complex Alu-rich genomic architecture. Our study uncovered hidden genetic variation in NMNAT1-associated LCA and emphasized a shift from coding to noncoding regulatory mutations and repeat-mediated SVs in the molecular pathogenesis of heterogeneous recessive disorders such as hereditary blindness. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

Students Mental Representation of Biology Diagrams/Pictures Conventions Based on Formation of Causal Network

NASA Astrophysics Data System (ADS)

Sampurno, A. W.; Rahmat, A.; Diana, S.

2017-09-01

Diagrams/pictures conventions is one form of visual media that often used to assist students in understanding the biological concepts. The effectiveness of use diagrams/pictures in biology learning at school level has also been mostly reported. This study examines the ability of high school students in reading diagrams/pictures biological convention which is described by Mental Representation based on formation of causal networks. The study involved 30 students 11th grade MIA senior high school Banten Indonesia who are studying the excretory system. MR data obtained by Instrument worksheet, developed based on CNET-protocol, in which there are diagrams/drawings of nephron structure and urinary mechanism. Three patterns formed MR, namely Markov chain, feedback control with a single measurement, and repeated feedback control with multiple measurement. The third pattern is the most dominating pattern, differences in the pattern of MR reveal the difference in how and from which point the students begin to uncover important information contained in the diagram to establish a causal networks. Further analysis shows that a difference in the pattern of MR relate to how complex the students process the information contained in the diagrams/pictures.

Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms

PubMed Central

Gallo, Eduardo F; Posner, Jonathan

2016-01-01

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by developmentally inappropriate levels of inattention and hyperactivity or impulsivity. The heterogeneity of its clinical manifestations and the differential responses to treatment and varied prognoses have long suggested myriad underlying causes. Over the past decade, clinical and basic research efforts have uncovered many behavioural and neurobiological alterations associated with ADHD, from genes to higher order neural networks. Here, we review the neurobiology of ADHD by focusing on neural circuits implicated in the disorder and discuss how abnormalities in circuitry relate to symptom presentation and treatment. We summarise the literature on genetic variants that are potentially related to the development of ADHD, and how these, in turn, might affect circuit function and relevant behaviours. Whether these underlying neurobiological factors are causally related to symptom presentation remains unresolved. Therefore, we assess efforts aimed at disentangling issues of causality, and showcase the shifting research landscape towards endophenotype refinement in clinical and preclinical settings. Furthermore, we review approaches being developed to understand the neurobiological underpinnings of this complex disorder including the use of animal models, neuromodulation, and pharmaco-imaging studies. PMID:27183902

DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework.

PubMed

Richmond, Rebecca C; Sharp, Gemma C; Ward, Mary E; Fraser, Abigail; Lyttleton, Oliver; McArdle, Wendy L; Ring, Susan M; Gaunt, Tom R; Lawlor, Debbie A; Davey Smith, George; Relton, Caroline L

2016-05-01

Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ∼1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Unethical conduct by the nurse: a critical discourse analysis of Nurses Tribunal inquiries.

PubMed

Dixon, Kathleen A

2013-08-01

The aim of this study was to uncover and critically examine hidden assumptions that underpin the findings of nurses' unethical conduct arising from inquiries conducted by the Nurses Tribunal in New South Wales. This was a qualitative study located within a post-structural theoretical framework. Transcripts of five inquiries conducted between 1998 and 2003 were analysed using critical discourse analysis. The findings revealed two dominant discourses that were drawn upon in the inquiries to construct nurses' conduct as unethical. These were discourses of trust and accountability. The way the nurses were spoken about during the inquiries was shaped by normalising judgements that were used to discursively position the nurse through narrative.

Redesigning the exploitation of wheat genetic resources.

PubMed

Longin, C Friedrich H; Reif, Jochen C

2014-10-01

More than half a million wheat genetic resources are resting in gene banks worldwide. Unlocking their hidden favorable genetic diversity for breeding is pivotal for enhancing grain yield potential, and averting future food shortages. Here, we propose exploiting recent advances in hybrid wheat technology to uncover the masked breeding values of wheat genetic resources. The gathered phenotypic information will enable a targeted choice of accessions with high value for pre-breeding among this plethora of genetic resources. We intend to provoke a paradigm shift in pre-breeding strategies for grain yield, moving away from allele mining toward genome-wide selection to bridge the yield gap between genetic resources and elite breeding pools. Copyright © 2014 Elsevier Ltd. All rights reserved.

Childhood Temperament: Passive Gene-Environment Correlation, Gene-Environment Interaction, and the Hidden Importance of the Family Environment

PubMed Central

Lemery-Chalfant, Kathryn; Kao, Karen; Swann, Gregory; Goldsmith, H. Hill

2013-01-01

Biological parents pass on genotypes to their children, as well as provide home environments that correlate with their genotypes; thus, the association between the home environment and children's temperament can be genetically (i.e. passive gene-environment correlation) or environmentally mediated. Furthermore, family environments may suppress or facilitate the heritability of children's temperament (i.e. gene-environment interaction). The sample comprised 807 twin pairs (M age = 7.93 years) from the longitudinal Wisconsin Twin Project. Important passive gene-environment correlations emerged, such that home environments were less chaotic for children with high Effortful Control, and this association was genetically mediated. Children with high Extraversion/Surgency experienced more chaotic home environments, and this correlation was also genetically mediated. In addition, heritability of children's temperament was moderated by home environments, such that Effortful Control and Extraversion/Surgency were more heritable in chaotic homes, and Negative Affectivity was more heritable under crowded or unsafe home conditions. Modeling multiple types of gene-environment interplay uncovered the complex role of genetic factors and the hidden importance of the family environment for children's temperament and development more generally. PMID:23398752

Hidden Structural Codes in Protein Intrinsic Disorder.

PubMed

Borkosky, Silvia S; Camporeale, Gabriela; Chemes, Lucía B; Risso, Marikena; Noval, María Gabriela; Sánchez, Ignacio E; Alonso, Leonardo G; de Prat Gay, Gonzalo

2017-10-17

Intrinsic disorder is a major structural category in biology, accounting for more than 30% of coding regions across the domains of life, yet consists of conformational ensembles in equilibrium, a major challenge in protein chemistry. Anciently evolved papillomavirus genomes constitute an unparalleled case for sequence to structure-function correlation in cases in which there are no folded structures. E7, the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of a handful of residues with absolute conservation, scattered along the sequence of its N-terminal intrinsically disordered domain, which intriguingly are mostly leucine residues. Mutation of these led to a pronounced increase in both α-helix and β-sheet structural content, reflected by drastic effects on equilibrium propensities and oligomerization kinetics, and uncovers the existence of local structural elements that oppose canonical folding. These folding relays suggest the existence of yet undefined hidden structural codes behind intrinsic disorder in this model protein. Thus, evolution pinpoints conformational hot spots that could have not been identified by direct experimental methods for analyzing or perturbing the equilibrium of an intrinsically disordered protein ensemble.

Endophytic actinobacteria: Diversity, secondary metabolism and mechanisms to unsilence biosynthetic gene clusters.

PubMed

Dinesh, Raghavan; Srinivasan, Veeraraghavan; T E, Sheeja; Anandaraj, Muthuswamy; Srambikkal, Hamza

2017-09-01

Endophytic actinobacteria, which reside in the inner tissues of host plants, are gaining serious attention due to their capacity to produce a plethora of secondary metabolites (e.g. antibiotics) possessing a wide variety of biological activity with diverse functions. This review encompasses the recent reports on endophytic actinobacterial species diversity, in planta habitats and mechanisms underlying their mode of entry into plants. Besides, their metabolic potential, novel bioactive compounds they produce and mechanisms to unravel their hidden metabolic repertoire by activation of cryptic or silent biosynthetic gene clusters (BGCs) for eliciting novel secondary metabolite production are discussed. The study also reviews the classical conservative techniques (chemical/biological/physical elicitation, co-culturing) as well as modern microbiology tools (e.g. next generation sequencing) that are being gainfully employed to uncover the vast hidden scaffolds for novel secondary metabolites produced by these endophytes, which would subsequently herald a revolution in drug engineering. The potential role of these endophytes in the agro-environment as promising biological candidates for inhibition of phytopathogens and the way forward to thoroughly exploit this unique microbial community by inducing expression of cryptic BGCs for encoding unseen products with novel therapeutic properties are also discussed.

Bacterial symbionts and natural products

PubMed Central

Crawford, Jason M.; Clardy, Jon

2011-01-01

The study of bacterial symbionts of eukaryotic hosts has become a powerful discovery engine for chemistry. This highlight looks at four case studies that exemplify the range of chemistry and biology involved in these symbioses: a bacterial symbiont of a fungus and a marine invertebrate that produce compounds with significant anticancer activity, and bacterial symbionts of insects and nematodes that produce compounds that regulate multilateral symbioses. In the last ten years, a series of shocking revelations – the molecular equivalents of a reality TV show’s uncovering the true parents of a well known individual or a deeply hidden family secret – altered the study of genetically encoded small molecules, natural products for short. These revelations all involved natural products produced by bacterial symbionts, and while details differed, two main plot lines emerged: parentage, in which the real producers of well known natural products with medical potential were not the organisms from which they were originally discovered, and hidden relationships, in which bacterially produced small molecules turned out to be the unsuspected regulators of complex interactions. For chemists, these studies led to new molecules, new biosynthetic pathways, and an understanding of the biological functions these molecules fulfill. PMID:21594283

The necessity of DNA taxonomy to reveal cryptic diversity and spatial distribution of meiofauna, with a focus on Nemertea.

PubMed

Leasi, Francesca; Norenburg, Jon L

2014-01-01

Meiofauna represent one of the most abundant and diverse communities in marine benthic ecosystems. However, an accurate assessment of diversity at the level of species has been and remains challenging for these microscopic organisms. Therefore, for many taxa, especially the soft body forms such as nemerteans, which often lack clear diagnostic morphological traits, DNA taxonomy is an effective means to assess species diversity. Morphological taxonomy of Nemertea is well documented as complicated by scarcity of unambiguous character states and compromised by diagnoses of a majority of species (and higher clades) being inadequate or based on ambiguous characters and character states. Therefore, recent studies have advocated for the primacy of molecular tools to solve the taxonomy of this group. DNA taxonomy uncovers possible hidden cryptic species, provides a coherent means to systematize taxa in definite clades, and also reveals possible biogeographic patterns. Here, we analyze diversity of nemertean species by considering the barcode region of the mitochondrial gene Cytochrome Oxidase subunit I (COI) and different species delineation approaches in order to infer evolutionarily significant units. In the aim to uncover actual diversity of meiofaunal nemerteans across different sites in Central America, COI sequences were obtained for specimens assigned here to the genera Cephalothrix, Ototyphlonemertes, and Tetrastemma-like worms, each commonly encountered in our sampling. Additional genetic, taxonomic, and geographic data of other specimens belonging to these genera were added from GenBank. Results are consistent across different DNA taxonomy approaches, and revealed (i) the presence of several hidden cryptic species and (ii) numerous potential misidentifications due to traditional taxonomy. (iii) We additionally test a possible biogeographic pattern of taxonomic units revealed by this study, and, except for a few cases, the putative species seem not to be widely distributed, in contrast to what traditional taxonomy would suggest for the recognized morphotypes.

Detecting Hidden Diversification Shifts in Models of Trait-Dependent Speciation and Extinction.

PubMed

Beaulieu, Jeremy M; O'Meara, Brian C

2016-07-01

The distribution of diversity can vary considerably from clade to clade. Attempts to understand these patterns often employ state-dependent speciation and extinction models to determine whether the evolution of a particular novel trait has increased speciation rates and/or decreased extinction rates. It is still unclear, however, whether these models are uncovering important drivers of diversification, or whether they are simply pointing to more complex patterns involving many unmeasured and co-distributed factors. Here we describe an extension to the popular state-dependent speciation and extinction models that specifically accounts for the presence of unmeasured factors that could impact diversification rates estimated for the states of any observed trait, addressing at least one major criticism of BiSSE (Binary State Speciation and Extinction) methods. Specifically, our model, which we refer to as HiSSE (Hidden State Speciation and Extinction), assumes that related to each observed state in the model are "hidden" states that exhibit potentially distinct diversification dynamics and transition rates than the observed states in isolation. We also demonstrate how our model can be used as character-independent diversification models that allow for a complex diversification process that is independent of the evolution of a character. Under rigorous simulation tests and when applied to empirical data, we find that HiSSE performs reasonably well, and can at least detect net diversification rate differences between observed and hidden states and detect when diversification rate differences do not correlate with the observed states. We discuss the remaining issues with state-dependent speciation and extinction models in general, and the important ways in which HiSSE provides a more nuanced understanding of trait-dependent diversification. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Speakable and Unspeakable in Quantum Mechanics

NASA Astrophysics Data System (ADS)

Bell, J. S.; Aspect, Introduction by Alain

2004-06-01

List of papers on quantum philosophy by J. S. Bell; Preface; Acknowledgements; Introduction by Alain Aspect; 1. On the problem of hidden variables in quantum mechanics; 2. On the Einstein-Rosen-Podolsky paradox; 3. The moral aspects of quantum mechanics; 4. Introduction to the hidden-variable question; 5. Subject and object; 6. On wave packet reduction in the Coleman-Hepp model; 7. The theory of local beables; 8. Locality in quantum mechanics: reply to critics; 9. How to teach special relativity; 10. Einstein-Podolsky-Rosen experiments; 11. The measurement theory of Everett and de Broglie's pilot wave; 12. Free variables and local causality; 13. Atomic-cascade photons and quantum-mechanical nonlocality; 14. de Broglie-Bohm delayed choice double-slit experiments and density matrix; 15. Quantum mechanics for cosmologists; 16. Bertlmann's socks and the nature of reality; 17. On the impossible pilot wave; 18. Speakable and unspeakable in quantum mechanics; 19. Beables for quantum field theory; 20. Six possible worlds of quantum mechanics; 21. EPR correlations and EPR distributions; 22. Are there quantum jumps?; 23. Against 'measurement'; 24. La Nouvelle cuisine.

Emergence of Space-Time Localization and Cosmic Decoherence:. More on Irreversible Time, Dark Energy, Anti-Matter and Black-Holes

NASA Astrophysics Data System (ADS)

Magnon, Anne

2005-04-01

A non geometric cosmology is presented, based on logic of observability, where logical categories of our perception set frontiers to comprehensibility. The Big-Bang singularity finds here a substitute (comparable to a "quantum jump"): a logical process (tied to self-referent and divisible totality) by which information emerges, focalizes on events and recycles, providing a transition from incoherence to causal coherence. This jump manufactures causal order and space-time localization, as exact solutions to Einstein's equation, where the last step of the process disentangles complex Riemann spheres into real null-cones (a geometric overturning imposed by self-reference, reminding us of our ability to project the cosmos within our mental sphere). Concepts such as antimatter and dark energy (dual entities tied to bifurcations or broken symmetries, and their compensation), are presented as hidden in the virtual potentialities, while irreversible time appears with the recycling of information and related flow. Logical bifurcations (such as the "part-totality" category, a quantum of information which owes its recycling to non localizable logical separations, as anticipated by unstability or horizon dependence of the quantum vacuum) induce broken symmetries, at the (complex or real) geometric level [eg. the antiselfdual complex non linear graviton solutions, which break duality symmetry, provide a model for (hidden) anti-matter, itself compensated with dark-energy, and providing, with space-time localization, the radiative gravitational energy (Bondi flux and related bifurcations of the peeling off type), as well as mass of isolated bodies]. These bifurcations are compensated by inertial effects (non geometric precursors of the Coriolis forces) able to explain (on logical grounds) the cosmic expansion (a repulsion?) and critical equilibrium of the cosmic tissue. Space-time environment, itself, emerges through the jump, as a censor to totality, a screen to incoherence (as anticipated by black-hole event horizons, cosmic censors able to shelter causal geometry). In analogy with black-hole singularities, the Big-Bang can be viewed as a geometric hint that a transition from incoherence to (causal space-time) localization and related coherence (comprehensibility), is taking place (space-time demolition, a reverse process towards incoherence or information recycling, is expected in the vicinity of singularities, as hinted by black-holes and related "time-machines"). A theory of the emergence of perception (and life?), in connection with observability and the function of partition (able to screen totality), is on its way [interface incoherence-coherence, sleeping and awaking states of localization, horizons of perception etc, are anticipated by black-hole event horizons, beyond which a non causal, dimensionless incoherent regime or memorization process, presents itself with the loss of localization, suggesting a unifying regime (ultimate energies?) hidden in cosmic potentialities]. The decoherence process presented here, suggests an ultimate interaction, expression of the logical relation of subsystems to totality, and to be identified to the flow of information or its recycling through cosmic jump (this is anticipated by the dissipation of distance or hierarchies on null-cones, themselves recycled with information and events). The geometric projection of this unified irreversible dynamics is expressed by unified Yang-Mills field equations (coupled to Einsteinian gravity). An ultimate form of action ("set"-volumes of information) presents itself, whose extrema can be achieved through extremal transfer of information and related partition of cells of information (thus anticipating the mitosis of living cells, possibly triggered at the non localizable level, as imposed by the logical regime of cosmic decoherence: participating subsystems ?). The matching of the objective and subjective facets of (information and) decoherences is perceived as contact with a reality.

Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height.

PubMed

Guo, Michael; Liu, Zun; Willen, Jessie; Shaw, Cameron P; Richard, Daniel; Jagoda, Evelyn; Doxey, Andrew C; Hirschhorn, Joel; Capellini, Terence D

2017-12-05

GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. To uncover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology, are enriched at height GWAS loci, particularly near differentially expressed growth plate genes, and enriched for binding motifs of transcription factors with roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at CHSY1 , we identified a candidate causal variant (rs9920291) overlapping an open chromatin region. Reporter assays demonstrated that rs9920291 shows allelic regulatory activity, and CRISPR/Cas9 targeting of human chondrocytes demonstrates that the region regulates CHSY1 expression. Thus, integrating biologically relevant epigenetic information (here, from growth plates) with genetic association results can identify biological mechanisms important for human growth.

Optogenetics in a transparent animal: circuit function in the larval zebrafish.

PubMed

Portugues, Ruben; Severi, Kristen E; Wyart, Claire; Ahrens, Misha B

2013-02-01

Optogenetic tools can be used to manipulate neuronal activity in a reversible and specific manner. In recent years, such methods have been applied to uncover causal relationships between activity in specified neuronal circuits and behavior in the larval zebrafish. In this small, transparent, genetic model organism, noninvasive manipulation and monitoring of neuronal activity with light is possible throughout the nervous system. Here we review recent work in which these new tools have been applied to zebrafish, and discuss some of the existing challenges of these approaches. Copyright © 2012. Published by Elsevier Ltd.

New and emerging pathogens in canine infectious respiratory disease.

PubMed

Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

2014-03-01

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Testing Bell's inequality with cosmic photons: closing the setting-independence loophole.

PubMed

Gallicchio, Jason; Friedman, Andrew S; Kaiser, David I

2014-03-21

We propose a practical scheme to use photons from causally disconnected cosmic sources to set the detectors in an experimental test of Bell's inequality. In current experiments, with settings determined by quantum random number generators, only a small amount of correlation between detector settings and local hidden variables, established less than a millisecond before each experiment, would suffice to mimic the predictions of quantum mechanics. By setting the detectors using pairs of quasars or patches of the cosmic microwave background, observed violations of Bell's inequality would require any such coordination to have existed for billions of years-an improvement of 20 orders of magnitude.

Nurse faculty experiences in problem-based learning: an interpretive phenomenologic analysis.

PubMed

Paige, Jane B; Smith, Regina O

2013-01-01

This study explored the nurse faculty experience of participating in a problem-based learning (PBL) faculty development program. Utilizing PBL as a pedagogical method requires a paradigm shift in the way faculty think about teaching, learning, and the teacher-student relationship. An interpretive phenomenological analysis approach was used to explore the faculty experience in a PBL development program. Four themes emerged: change in perception of the teacher-student relationship, struggle in letting go, uncertainty, and valuing PBL as a developmental process. Epistemic doubt happens when action and intent toward the PBL teaching perspective do not match underlying beliefs. Findings from this study call for ongoing administrative support for education on PBL while faculty take time to uncover hidden epistemological beliefs.

Competing magnetostructural phases in a semiclassical system

NASA Astrophysics Data System (ADS)

O'Neal, Kenneth R.; Lee, Jun Hee; Kim, Maeng-Suk; Manson, Jamie L.; Liu, Zhenxian; Fishman, Randy S.; Musfeldt, Janice L.

2017-11-01

The interplay between charge, structure, and magnetism gives rise to rich phase diagrams in complex materials with exotic properties emerging when phases compete. Molecule-based materials are particularly advantageous in this regard due to their low energy scales, flexible lattices, and chemical tunability. Here, we bring together high pressure Raman scattering, modeling, and first principles calculations to reveal the pressure-temperature-magnetic field phase diagram of Mn[N(CN)2]2. We uncover how hidden soft modes involving octahedral rotations drive two pressure-induced transitions triggering the low → high magnetic anisotropy crossover and a unique reorientation of exchange planes. These magnetostructural transitions and their mechanisms highlight the importance of spin-lattice interactions in establishing phases with novel magnetic properties in Mn(II)-containing systems.

Cultural Differences in Perceptual Reorganization in US and Pirahã Adults

PubMed Central

Yoon, Jennifer M. D.; Witthoft, Nathan; Winawer, Jonathan; Frank, Michael C.; Everett, Daniel L.; Gibson, Edward

2014-01-01

Visual illusions and other perceptual phenomena can be used as tools to uncover the otherwise hidden constructive processes that give rise to perception. Although many perceptual processes are assumed to be universal, variable susceptibility to certain illusions and perceptual effects across populations suggests a role for factors that vary culturally. One striking phenomenon is seen with two-tone images—photos reduced to two tones: black and white. Deficient recognition is observed in young children under conditions that trigger automatic recognition in adults. Here we show a similar lack of cue-triggered perceptual reorganization in the Pirahã, a hunter-gatherer tribe with limited exposure to modern visual media, suggesting such recognition is experience- and culture-specific. PMID:25411970

Topology versus Anderson localization: Nonperturbative solutions in one dimension

NASA Astrophysics Data System (ADS)

Altland, Alexander; Bagrets, Dmitry; Kamenev, Alex

2015-02-01

We present an analytic theory of quantum criticality in quasi-one-dimensional topological Anderson insulators. We describe these systems in terms of two parameters (g ,χ ) representing localization and topological properties, respectively. Certain critical values of χ (half-integer for Z classes, or zero for Z2 classes) define phase boundaries between distinct topological sectors. Upon increasing system size, the two parameters exhibit flow similar to the celebrated two-parameter flow of the integer quantum Hall insulator. However, unlike the quantum Hall system, an exact analytical description of the entire phase diagram can be given in terms of the transfer-matrix solution of corresponding supersymmetric nonlinear sigma models. In Z2 classes we uncover a hidden supersymmetry, present at the quantum critical point.

Temporal Expression Profiling Identifies Pathways Mediating Effect of Causal Variant on Phenotype

PubMed Central

Gupta, Saumya; Radhakrishnan, Aparna; Raharja-Liu, Pandu; Lin, Gen; Steinmetz, Lars M.; Gagneur, Julien; Sinha, Himanshu

2015-01-01

Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants’ effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage of analyzing allele-specific transcriptional dynamics of mediating genes. Applications in higher eukaryotes can be valuable for inferring causal molecular pathways underlying complex dynamic processes, such as development, physiology and disease progression. PMID:26039065

Sex allocation theory reveals a hidden cost of neonicotinoid exposure in a parasitoid wasp

PubMed Central

Whitehorn, Penelope R.; Cook, Nicola; Blackburn, Charlotte V.; Gill, Sophie M.; Green, Jade; Shuker, David M.

2015-01-01

Sex allocation theory has proved to be one the most successful theories in evolutionary ecology. However, its role in more applied aspects of ecology has been limited. Here we show how sex allocation theory helps uncover an otherwise hidden cost of neonicotinoid exposure in the parasitoid wasp Nasonia vitripennis. Female N. vitripennis allocate the sex of their offspring in line with Local Mate Competition (LMC) theory. Neonicotinoids are an economically important class of insecticides, but their deployment remains controversial, with evidence linking them to the decline of beneficial species. We demonstrate for the first time to our knowledge, that neonicotinoids disrupt the crucial reproductive behaviour of facultative sex allocation at sub-lethal, field-relevant doses in N. vitripennis. The quantitative predictions we can make from LMC theory show that females exposed to neonicotinoids are less able to allocate sex optimally and that this failure imposes a significant fitness cost. Our work highlights that understanding the ecological consequences of neonicotinoid deployment requires not just measures of mortality or even fecundity reduction among non-target species, but also measures that capture broader fitness costs, in this case offspring sex allocation. Our work also highlights new avenues for exploring how females obtain information when allocating sex under LMC. PMID:25925105

Uncovering the cognitive processes underlying mental rotation: an eye-movement study.

PubMed

Xue, Jiguo; Li, Chunyong; Quan, Cheng; Lu, Yiming; Yue, Jingwei; Zhang, Chenggang

2017-08-30

Mental rotation is an important paradigm for spatial ability. Mental-rotation tasks are assumed to involve five or three sequential cognitive-processing states, though this has not been demonstrated experimentally. Here, we investigated how processing states alternate during mental-rotation tasks. Inference was carried out using an advanced statistical modelling and data-driven approach - a discriminative hidden Markov model (dHMM) trained using eye-movement data obtained from an experiment consisting of two different strategies: (I) mentally rotate the right-side figure to be aligned with the left-side figure and (II) mentally rotate the left-side figure to be aligned with the right-side figure. Eye movements were found to contain the necessary information for determining the processing strategy, and the dHMM that best fit our data segmented the mental-rotation process into three hidden states, which we termed encoding and searching, comparison, and searching on one-side pair. Additionally, we applied three classification methods, logistic regression, support vector model and dHMM, of which dHMM predicted the strategies with the highest accuracy (76.8%). Our study did confirm that there are differences in processing states between these two of mental-rotation strategies, and were consistent with the previous suggestion that mental rotation is discrete process that is accomplished in a piecemeal fashion.

High-resolution definition of the Vibrio cholerae essential gene set with hidden Markov model–based analyses of transposon-insertion sequencing data

PubMed Central

Chao, Michael C.; Pritchard, Justin R.; Zhang, Yanjia J.; Rubin, Eric J.; Livny, Jonathan; Davis, Brigid M.; Waldor, Matthew K.

2013-01-01

The coupling of high-density transposon mutagenesis to high-throughput DNA sequencing (transposon-insertion sequencing) enables simultaneous and genome-wide assessment of the contributions of individual loci to bacterial growth and survival. We have refined analysis of transposon-insertion sequencing data by normalizing for the effect of DNA replication on sequencing output and using a hidden Markov model (HMM)-based filter to exploit heretofore unappreciated information inherent in all transposon-insertion sequencing data sets. The HMM can smooth variations in read abundance and thereby reduce the effects of read noise, as well as permit fine scale mapping that is independent of genomic annotation and enable classification of loci into several functional categories (e.g. essential, domain essential or ‘sick’). We generated a high-resolution map of genomic loci (encompassing both intra- and intergenic sequences) that are required or beneficial for in vitro growth of the cholera pathogen, Vibrio cholerae. This work uncovered new metabolic and physiologic requirements for V. cholerae survival, and by combining transposon-insertion sequencing and transcriptomic data sets, we also identified several novel noncoding RNA species that contribute to V. cholerae growth. Our findings suggest that HMM-based approaches will enhance extraction of biological meaning from transposon-insertion sequencing genomic data. PMID:23901011

Dynamic Alignment Models for Neural Coding

PubMed Central

Kollmorgen, Sepp; Hahnloser, Richard H. R.

2014-01-01

Recently, there have been remarkable advances in modeling the relationships between the sensory environment, neuronal responses, and behavior. However, most models cannot encompass variable stimulus-response relationships such as varying response latencies and state or context dependence of the neural code. Here, we consider response modeling as a dynamic alignment problem and model stimulus and response jointly by a mixed pair hidden Markov model (MPH). In MPHs, multiple stimulus-response relationships (e.g., receptive fields) are represented by different states or groups of states in a Markov chain. Each stimulus-response relationship features temporal flexibility, allowing modeling of variable response latencies, including noisy ones. We derive algorithms for learning of MPH parameters and for inference of spike response probabilities. We show that some linear-nonlinear Poisson cascade (LNP) models are a special case of MPHs. We demonstrate the efficiency and usefulness of MPHs in simulations of both jittered and switching spike responses to white noise and natural stimuli. Furthermore, we apply MPHs to extracellular single and multi-unit data recorded in cortical brain areas of singing birds to showcase a novel method for estimating response lag distributions. MPHs allow simultaneous estimation of receptive fields, latency statistics, and hidden state dynamics and so can help to uncover complex stimulus response relationships that are subject to variable timing and involve diverse neural codes. PMID:24625448

Comparative Analysis of Proteomes and Functionomes Provides Insights into Origins of Cellular Diversification

PubMed Central

Caetano-Anollés, Gustavo

2013-01-01

Reconstructing the evolutionary history of modern species is a difficult problem complicated by the conceptual and technical limitations of phylogenetic tree building methods. Here, we propose a comparative proteomic and functionomic inferential framework for genome evolution that allows resolving the tripartite division of cells and sketching their history. Evolutionary inferences were derived from the spread of conserved molecular features, such as molecular structures and functions, in the proteomes and functionomes of contemporary organisms. Patterns of use and reuse of these traits yielded significant insights into the origins of cellular diversification. Results uncovered an unprecedented strong evolutionary association between Bacteria and Eukarya while revealing marked evolutionary reductive tendencies in the archaeal genomic repertoires. The effects of nonvertical evolutionary processes (e.g., HGT, convergent evolution) were found to be limited while reductive evolution and molecular innovation appeared to be prevalent during the evolution of cells. Our study revealed a strong vertical trace in the history of proteins and associated molecular functions, which was reliably recovered using the comparative genomics approach. The trace supported the existence of a stem line of descent and the very early appearance of Archaea as a diversified superkingdom, but failed to uncover a hidden canonical pattern in which Bacteria was the first superkingdom to deploy superkingdom-specific structures and functions. PMID:24492748

Uncovering the unknown: A grounded theory study exploring the impact of self-awareness on the culture of feedback in residency education.

PubMed

Ramani, Subha; Könings, Karen; Mann, Karen V; van der Vleuten, Cees

2017-10-01

Self-assessment and reflection are essential for meaningful feedback. We aimed to explore whether the well-known Johari window model of self-awareness could guide feedback conversations between faculty and residents and enhance the institutional feedback culture. We had previously explored perceptions of residents and faculty regarding sociocultural factors impacting feedback. We re-analyzed data targeting themes related to self-assessment, reflection, feedback seeking and acceptance, aiming to generate individual and institutional feedback strategies applicable to each quadrant of the window. We identified the following themes for each quadrant: (1) Behaviors known to self and others - Validating the known; (2) Behaviors unknown to self but known to others - Accepting the blind; (3) Behaviors known to self and unknown to others - Disclosure of hidden; and (4) Behaviors unknown to self and others - Uncovering the unknown. Normalizing self-disclosure of limitations, encouraging feedback seeking, training in nonjudgmental feedback and providing opportunities for longitudinal relationships could promote self-awareness, ultimately expanding the "open" quadrant of the Johari window. The Johari window, a model of self-awareness in interpersonal communications, could provide a robust framework for individuals to improve their feedback conversations and institutions to design feedback initiatives that enhance its quality and impact.

Machine learning for neuroimaging with scikit-learn.

PubMed

Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael; Gervais, Philippe; Mueller, Andreas; Kossaifi, Jean; Gramfort, Alexandre; Thirion, Bertrand; Varoquaux, Gaël

2014-01-01

Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g., multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g., resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain.

Machine learning for neuroimaging with scikit-learn

PubMed Central

Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael; Gervais, Philippe; Mueller, Andreas; Kossaifi, Jean; Gramfort, Alexandre; Thirion, Bertrand; Varoquaux, Gaël

2014-01-01

Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g., multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g., resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain. PMID:24600388

Uncovering Metaethical Assumptions in Bioethical Discourse across Cultures.

PubMed

Sullivan, Laura Specker

2016-03-01

Much of bioethical discourse now takes place across cultures. This does not mean that cross-cultural understanding has increased. Many cross-cultural bioethical discussions are marked by entrenched disagreement about whether and why local practices are justified. In this paper, I argue that a major reason for these entrenched disagreements is that problematic metaethical commitments are hidden in these cross-cultural discourses. Using the issue of informed consent in East Asia as an example of one such discourse, I analyze two representative positions in the discussion and identify their metaethical commitments. I suggest that the metaethical assumptions of these positions result from their shared method of ethical justification: moral principlism. I then show why moral principlism is problematic in cross-cultural analyses and propose a more useful method for pursuing ethical justification across cultures.

Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.

PubMed

Díaz-Muñoz, Manuel D; Turner, Martin

2018-01-01

Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome.

The multifaceted interplay between lipids and epigenetics.

PubMed

Dekkers, Koen F; Slagboom, P Eline; Jukema, J Wouter; Heijmans, Bastiaan T

2016-06-01

The interplay between lipids and epigenetic mechanisms has recently gained increased interest because of its relevance for common diseases and most notably atherosclerosis. This review discusses recent advances in unravelling this interplay with a particular focus on promising approaches and methods that will be able to establish causal relationships. Complementary approaches uncovered close links between circulating lipids and epigenetic mechanisms at multiple levels. A characterization of lipid-associated genetic variants suggests that these variants exert their influence on lipid levels through epigenetic changes in the liver. Moreover, exposure of monocytes to lipids persistently alters their epigenetic makeup resulting in more proinflammatory cells. Hence, epigenetic changes can both impact on and be induced by lipids. It is the combined application of technological advances to probe epigenetic modifications at a genome-wide scale and methodological advances aimed at causal inference (including Mendelian randomization and integrative genomics) that will elucidate the interplay between circulating lipids and epigenetics. Understanding its role in the development of atherosclerosis holds the promise of identifying a new category of therapeutic targets, since epigenetic changes are amenable to reversal.

Higher Education and Health Investments: Does More Schooling Affect Preventive Health Care Use?◆

PubMed Central

Fletcher, Jason M.; Frisvold, David E.

2012-01-01

While it is well-known that individuals with higher levels of education consume more preventive medical care, there are several potential explanations for this stylized fact. These explanations include causal and non-causal mechanisms, and distinguishing among explanations is relevant for accessing the importance of educational spillovers on lifetime health outcomes as well as uncovering the determinants of preventive care. In this paper, we use regression analysis, sibling fixed effects, and matching estimators to examine the impact of education on preventive care. In particular, we use a cohort of 10,000 Wisconsin high school graduates that has been followed for nearly 50 years and find evidence that attending college is associated with an increase in the likelihood of using several types of preventive care by approximately five to fifteen percent for college attendees in the early 1960s. We also find that greater education may influence preventive care partly through occupational channels and access to care. These findings suggest that increases in education have the potential to spillover on long-term health choices. PMID:22368727

Electronic Tuning In The Hidden Order Compound URu2Si 2 Through Si → P substitution

NASA Astrophysics Data System (ADS)

Gallagher, Andrew

Crystalline materials that include 4f- and 5 f-electron elements frequently exhibit a variety of intriguing phenomena including spin and charge orderings, spin and valence fluctuations, heavy fermion behavior, breakdown of Fermi liquid behavior, and unconventional superconductivity. [5, 6, 7, 8, 9, 10, 11, 12, 13] Amongst such materials, the Kondo lattice system URu2Si2 stands out as being particularly unusual. [14, 15, 16] While at high temperature it exhibits behavior that is typical for an f-electron lattice immersed in a sea of conduction electrons, at T0 = 17:5 K there is a second order phase transition that is followed by unconventional superconductivity near Tc ≈ 1:5 K. [15] Despite three decades of work, the order parameter for the transition at T0 remains unknown and hence, it has been named "hidden order". There have been a multitude of experimental attempts to unravel hidden order, mainly through tuning of the electronic state via pressure, applied magnetic field, and chemical substitution. [17, 18] While these strategies reveal interesting phase diagrams, a longstanding challenge is that any such approach explores the phase space along an unknown vector: i.e., many different factors are affected. To address this issue, we developed a new organizational map for the U-based ThCr2Si2-type compounds that are related to URu2Si2 and thus guided, we explored a new chemical tuning axis: Si -> P. Our studies were enabled by the development of a new molten metal crystal growth method for URu2Si2 which produces high quality single crystals and allows us to introduce high vapor pressure elements, such as phosphorous. [19, 20] Si → P tuning reveals that while the high temperature Kondo lattice behavior is robust, the low temperature phenomena are remarkably sensitive to electronic tuning. [21, 22] In the URu2Si2-xPx phase diagram we find that while hidden order is monotonically suppressed and destroyed for x < 0.035, the superconducting strength evolves non-monotonically with a maximum near x = 0.01 and that superconductivity is destroyed near x ≈ 0.028. For 0.03 < x < 0.26 there is a region with Kondo coherence but no ordered state. Antiferromagnetism abruptly appears for x = 0.26. This phase diagram differs significantly from those produced by most other tuning strategies in URu2Si2, including applied pressure, and isoelectronic chemical substitution (i.e. Ru→Fe and Os), where hidden order and magnetism share a common phase boundary. [2, 23, 24] We discuss implications for understanding hidden order, its relationship to magnetism, and prospects for uncovering novel sibling electronic states.

Improved methods for multi-trait fine mapping of pleiotropic risk loci.

PubMed

Kichaev, Gleb; Roytman, Megan; Johnson, Ruth; Eskin, Eleazar; Lindström, Sara; Kraft, Peter; Pasaniuc, Bogdan

2017-01-15

Genome-wide association studies (GWAS) have identified thousands of regions in the genome that contain genetic variants that increase risk for complex traits and diseases. However, the variants uncovered in GWAS are typically not biologically causal, but rather, correlated to the true causal variant through linkage disequilibrium (LD). To discern the true causal variant(s), a variety of statistical fine-mapping methods have been proposed to prioritize variants for functional validation. In this work we introduce a new approach, fastPAINTOR, that leverages evidence across correlated traits, as well as functional annotation data, to improve fine-mapping accuracy at pleiotropic risk loci. To improve computational efficiency, we describe an new importance sampling scheme to perform model inference. First, we demonstrate in simulations that by leveraging functional annotation data, fastPAINTOR increases fine-mapping resolution relative to existing methods. Next, we show that jointly modeling pleiotropic risk regions improves fine-mapping resolution compared to standard single trait and pleiotropic fine mapping strategies. We report a reduction in the number of SNPs required for follow-up in order to capture 90% of the causal variants from 23 SNPs per locus using a single trait to 12 SNPs when fine-mapping two traits simultaneously. Finally, we analyze summary association data from a large-scale GWAS of lipids and show that these improvements are largely sustained in real data. The fastPAINTOR framework is implemented in the PAINTOR v3.0 package which is publicly available to the research community http://bogdan.bioinformatics.ucla.edu/software/paintor CONTACT: gkichaev@ucla.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System

PubMed Central

Díaz-Muñoz, Manuel D.; Turner, Martin

2018-01-01

Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome. PMID:29875770

Domestic science: making chemistry your cup of tea.

PubMed

Keene, Melanie

2008-03-01

In the early Victorian home, there were plenty of scientific lessons to be uncovered. With the appropriate interrogation, everyday objects could transform seemingly mundane activities such as eating breakfast, washing clothes or reading by candle-light into household lectures that gave children a familiar base from which to explore the hidden properties and marvellous histories of common commodities. Responding to an unprecedented hunger for scientific knowledge, a profusion of introductory texts appeared in the mid-nineteenth century that directed lessons into homes across Britain and beyond. In particular, the science of chemistry found its way into this domestic setting, as writers promoted its practice and practitioners as a source of authoritative expertise on everyday life. One of the most compelling illustrations of this encounter between the public and chemistry took place over a simple cup of tea.

Suppression bias at the Journal of Occupational and Environmental Medicine.

PubMed

Egilman, David S

2005-01-01

When the Journal of Occupational and Environmental Medicine rejected an article on corporate suppression of science on the grounds that the topic "was not a high priority" for journal readers, the author bought advertising space in JOEM to present his findings. The JOEM editor regretted he had not seen the ad to prevent its publication, and subsequently allowed the corporate-sponsored authors of a criticized study to respond to the advertisement. The editor then refused to allow the ad's author to respond in turn, suppressing scientific information with the apparent intent of protecting the interests and profits of the corporate sponsor. A reputable journal has a responsibility to eschew corporate interests and work to uncover science hidden by interests that do not prioritize the pursuit of truth. JOEM needs to re-examine its priorities.

Observer-Pattern Modeling and Slow-Scale Bifurcation Analysis of Two-Stage Boost Inverters

NASA Astrophysics Data System (ADS)

Zhang, Hao; Wan, Xiaojin; Li, Weijie; Ding, Honghui; Yi, Chuanzhi

2017-06-01

This paper deals with modeling and bifurcation analysis of two-stage Boost inverters. Since the effect of the nonlinear interactions between source-stage converter and load-stage inverter causes the “hidden” second-harmonic current at the input of the downstream H-bridge inverter, an observer-pattern modeling method is proposed by removing time variance originating from both fundamental frequency and hidden second harmonics in the derived averaged equations. Based on the proposed observer-pattern model, the underlying mechanism of slow-scale instability behavior is uncovered with the help of eigenvalue analysis method. Then eigenvalue sensitivity analysis is used to select some key system parameters of two-stage Boost inverter, and some behavior boundaries are given to provide some design-oriented information for optimizing the circuit. Finally, these theoretical results are verified by numerical simulations and circuit experiment.

Automation and adaptation: Nurses' problem-solving behavior following the implementation of bar coded medication administration technology.

PubMed

Holden, Richard J; Rivera-Rodriguez, A Joy; Faye, Héléne; Scanlon, Matthew C; Karsh, Ben-Tzion

2013-08-01

The most common change facing nurses today is new technology, particularly bar coded medication administration technology (BCMA). However, there is a dearth of knowledge on how BCMA alters nursing work. This study investigated how BCMA technology affected nursing work, particularly nurses' operational problem-solving behavior. Cognitive systems engineering observations and interviews were conducted after the implementation of BCMA in three nursing units of a freestanding pediatric hospital. Problem-solving behavior, associated problems, and goals, were specifically defined and extracted from observed episodes of care. Three broad themes regarding BCMA's impact on problem solving were identified. First, BCMA allowed nurses to invent new problem-solving behavior to deal with pre-existing problems. Second, BCMA made it difficult or impossible to apply some problem-solving behaviors that were commonly used pre-BCMA, often requiring nurses to use potentially risky workarounds to achieve their goals. Third, BCMA created new problems that nurses were either able to solve using familiar or novel problem-solving behaviors, or unable to solve effectively. Results from this study shed light on hidden hazards and suggest three critical design needs: (1) ecologically valid design; (2) anticipatory control; and (3) basic usability. Principled studies of the actual nature of clinicians' work, including problem solving, are necessary to uncover hidden hazards and to inform health information technology design and redesign.

Sex allocation theory reveals a hidden cost of neonicotinoid exposure in a parasitoid wasp.

PubMed

Whitehorn, Penelope R; Cook, Nicola; Blackburn, Charlotte V; Gill, Sophie M; Green, Jade; Shuker, David M

2015-05-22

Sex allocation theory has proved to be one the most successful theories in evolutionary ecology. However, its role in more applied aspects of ecology has been limited. Here we show how sex allocation theory helps uncover an otherwise hidden cost of neonicotinoid exposure in the parasitoid wasp Nasonia vitripennis. Female N. vitripennis allocate the sex of their offspring in line with Local Mate Competition (LMC) theory. Neonicotinoids are an economically important class of insecticides, but their deployment remains controversial, with evidence linking them to the decline of beneficial species. We demonstrate for the first time to our knowledge, that neonicotinoids disrupt the crucial reproductive behaviour of facultative sex allocation at sub-lethal, field-relevant doses in N. vitripennis. The quantitative predictions we can make from LMC theory show that females exposed to neonicotinoids are less able to allocate sex optimally and that this failure imposes a significant fitness cost. Our work highlights that understanding the ecological consequences of neonicotinoid deployment requires not just measures of mortality or even fecundity reduction among non-target species, but also measures that capture broader fitness costs, in this case offspring sex allocation. Our work also highlights new avenues for exploring how females obtain information when allocating sex under LMC. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Automation and adaptation: Nurses’ problem-solving behavior following the implementation of bar coded medication administration technology

PubMed Central

Holden, Richard J.; Rivera-Rodriguez, A. Joy; Faye, Héléne; Scanlon, Matthew C.; Karsh, Ben-Tzion

2012-01-01

The most common change facing nurses today is new technology, particularly bar coded medication administration technology (BCMA). However, there is a dearth of knowledge on how BCMA alters nursing work. This study investigated how BCMA technology affected nursing work, particularly nurses’ operational problem-solving behavior. Cognitive systems engineering observations and interviews were conducted after the implementation of BCMA in three nursing units of a freestanding pediatric hospital. Problem-solving behavior, associated problems, and goals, were specifically defined and extracted from observed episodes of care. Three broad themes regarding BCMA’s impact on problem solving were identified. First, BCMA allowed nurses to invent new problem-solving behavior to deal with pre-existing problems. Second, BCMA made it difficult or impossible to apply some problem-solving behaviors that were commonly used pre-BCMA, often requiring nurses to use potentially risky workarounds to achieve their goals. Third, BCMA created new problems that nurses were either able to solve using familiar or novel problem-solving behaviors, or unable to solve effectively. Results from this study shed light on hidden hazards and suggest three critical design needs: (1) ecologically valid design; (2) anticipatory control; and (3) basic usability. Principled studies of the actual nature of clinicians’ work, including problem solving, are necessary to uncover hidden hazards and to inform health information technology design and redesign. PMID:24443642

Schooling in adolescence raises IQ scores

PubMed Central

Brinch, Christian N.; Galloway, Taryn Ann

2012-01-01

Although some scholars maintain that education has little effect on intelligence quotient (IQ) scores, others claim that IQ scores are indeed malleable, primarily through intervention in early childhood. The causal effect of education on IQ at later ages is often difficult to uncover because analyses based on observational data are plagued by problems of reverse causation and self-selection into further education. We exploit a reform that increased compulsory schooling from 7 to 9 y in Norway in the 1960s to estimate the effect of education on IQ. We find that this schooling reform, which primarily affected education in the middle teenage years, had a substantial effect on IQ scores measured at the age of 19 y. PMID:22203952

Variation of BMP3 Contributes to Dog Breed Skull Diversity

PubMed Central

Schoenebeck, Jeffrey J.; Hutchinson, Sarah A.; Byers, Alexandra; Beale, Holly C.; Carrington, Blake; Faden, Daniel L.; Rimbault, Maud; Decker, Brennan; Kidd, Jeffrey M.; Sood, Raman; Boyko, Adam R.; Fondon, John W.; Wayne, Robert K.; Bustamante, Carlos D.; Ciruna, Brian; Ostrander, Elaine A.

2012-01-01

Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait. PMID:22876193

A Rule-Based Spatial Reasoning Approach for OpenStreetMap Data Quality Enrichment; Case Study of Routing and Navigation

PubMed Central

2017-01-01

Finding relevant geospatial information is increasingly critical because of the growing volume of geospatial data available within the emerging “Big Data” era. Users are expecting that the availability of massive datasets will create more opportunities to uncover hidden information and answer more complex queries. This is especially the case with routing and navigation services where the ability to retrieve points of interest and landmarks make the routing service personalized, precise, and relevant. In this paper, we propose a new geospatial information approach that enables the retrieval of implicit information, i.e., geospatial entities that do not exist explicitly in the available source. We present an information broker that uses a rule-based spatial reasoning algorithm to detect topological relations. The information broker is embedded into a framework where annotations and mappings between OpenStreetMap data attributes and external resources, such as taxonomies, support the enrichment of queries to improve the ability of the system to retrieve information. Our method is tested with two case studies that leads to enriching the completeness of OpenStreetMap data with footway crossing points-of-interests as well as building entrances for routing and navigation purposes. It is concluded that the proposed approach can uncover implicit entities and contribute to extract required information from the existing datasets. PMID:29088125

Application of Deep Learning and Supervised Learning Methods to Recognize Nonlinear Hidden Pattern in Water Stress Levels from Spatiotemporal Datasets across Rural and Urban US Counties

NASA Astrophysics Data System (ADS)

Eisenhart, T.; Josset, L.; Rising, J. A.; Devineni, N.; Lall, U.

2017-12-01

In the wake of recent water crises, the need to understand and predict the risk of water stress in urban and rural areas has grown. This understanding has the potential to improve decision making in public resource management, policy making, risk management and investment decisions. Assuming an underlying relationship between urban and rural water stress and observable features, we apply Deep Learning and Supervised Learning models to uncover hidden nonlinear patterns from spatiotemporal datasets. Results of interest includes prediction accuracy on extreme categories (i.e. urban areas highly prone to water stress) and not solely the average risk for urban or rural area, which adds complexity to the tuning of model parameters. We first label urban water stressed counties using annual water quality violations and compile a comprehensive spatiotemporal dataset that captures the yearly evolution of climatic, demographic and economic factors of more than 3,000 US counties over the 1980-2010 period. As county-level data reporting is not done on a yearly basis, we test multiple imputation methods to get around the issue of missing data. Using Python libraries, TensorFlow and scikit-learn, we apply and compare the ability of, amongst other methods, Recurrent Neural Networks (testing both LSTM and GRU cells), Convolutional Neural Networks and Support Vector Machines to predict urban water stress. We evaluate the performance of those models over multiple time spans and combine methods to diminish the risk of overfitting and increase prediction power on test sets. This methodology seeks to identify hidden nonlinear patterns to assess the predominant data features that influence urban and rural water stress. Results from this application at the national scale will assess the performance of deep learning models to predict water stress risk areas across all US counties and will highlight a predominant Machine Learning method for modeling water stress risk using spatiotemporal data.

Learning history and cholinergic modulation in the dorsal hippocampus are necessary for rats to infer the status of a hidden event.

PubMed

Fast, Cynthia D; Flesher, M Melissa; Nocera, Nathanial A; Fanselow, Michael S; Blaisdell, Aaron P

2016-06-01

Identifying statistical patterns between environmental stimuli enables organisms to respond adaptively when cues are later observed. However, stimuli are often obscured from detection, necessitating behavior under conditions of ambiguity. Considerable evidence indicates decisions under ambiguity rely on inference processes that draw on past experiences to generate predictions under novel conditions. Despite the high demand for this process and the observation that it deteriorates disproportionately with age, the underlying mechanisms remain unknown. We developed a rodent model of decision-making during ambiguity to examine features of experience that contribute to inference. Rats learned either a simple (positive patterning) or complex (negative patterning) instrumental discrimination between the illumination of one or two lights. During test, only one light was lit while the other relevant light was blocked from physical detection (covered by an opaque shield, rendering its status ambiguous). We found experience with the complex negative patterning discrimination was necessary for rats to behave sensitively to the ambiguous test situation. These rats behaved as if they inferred the presence of the hidden light, responding differently than when the light was explicitly absent (uncovered and unlit). Differential expression profiles of the immediate early gene cFos indicated hippocampal involvement in the inference process while localized microinfusions of the muscarinic antagonist, scopolamine, into the dorsal hippocampus caused rats to behave as if only one light was present. That is, blocking cholinergic modulation prevented the rat from inferring the presence of the hidden light. Collectively, these results suggest cholinergic modulation mediates recruitment of hippocampal processes related to past experiences and transfer of these processes to make decisions during ambiguous situations. Our results correspond with correlations observed between human brain function and inference abilities, suggesting our experiments may inform interventions to alleviate or prevent cognitive dysfunction. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Single dose testosterone administration modulates emotional reactivity and counterfactual choice in healthy males.

PubMed

Wu, Yin; Clark, Luke; Zilioli, Samuele; Eisenegger, Christoph; Gillan, Claire M; Deng, Huihua; Li, Hong

2018-04-01

Testosterone has been implicated in the regulation of emotional responses and risky decision-making. However, the causal effect of testosterone upon emotional decision-making, especially in non-social settings, is still unclear. The present study investigated the role of testosterone in counterfactual thinking: regret is an intense negative emotion that arises from comparison of an obtained outcome from a decision against a better, non-obtained (i.e. counterfactual) alternative. Healthy male participants (n = 64) received a single-dose of 150 mg testosterone Androgel in a double-blind, placebo-controlled, between-participants design. At 180 min post-administration, participants performed the counterfactual thinking task. We applied a computational model derived from behavioral economic principles to uncover latent decision-making mechanisms that may be invisible in simple choice analyses. Our data showed that testosterone increased the ability to use anticipated regret to guide choice behavior, while reducing choice based on expected value. On affective ratings, testosterone increased sensitivity to both obtained and counterfactual outcomes. These findings provide evidence that testosterone causally modulates emotional decision-making, and highlight the role of testosterone in affective sensitivity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Claiming space for an engaged anthropology: spatial inequality and social exclusion.

PubMed

Low, Setha M

2011-01-01

I use the concept of “engaged anthropology” to frame a discussion of how “spatializing culture” uncovers systems of exclusion that are hidden or naturalized and thus rendered invisible to other methodological approaches. “Claiming Space for an Engaged Anthropology” is doubly meant: to claim more intellectual and professional space for engagement and to propose that anthropology include the dimension of space as a theoretical construct. I draw on three fieldwork examples to illustrate the value of the approach: (1) a Spanish American plaza, reclaimed from a Eurocentric past, for indigenous groups and contemporary cultural interpretation; (2) Moore Street Market, an enclosed Latino food market in Brooklyn, New York, reclaimed for a translocal set of social relations rather than a gentrified redevelopment project; (3) gated communities in Texas and New York and cooperatives in New York, reclaiming public space and confronting race and class segregation created by neoliberal enclosure and securitization.

Network features of sector indexes spillover effects in China: A multi-scale view

NASA Astrophysics Data System (ADS)

Feng, Sida; Huang, Shupei; Qi, Yabin; Liu, Xueyong; Sun, Qingru; Wen, Shaobo

2018-04-01

The spillover effects among sectors are of concern for distinct market participants, who are in distinct investment horizons and concerned with the information in different time scales. In order to uncover the hidden spillover information in multi-time scales in the rapidly changing stock market and thereby offer guidance to different investors concerning distinct time scales from a system perspective, this paper constructed directional spillover effect networks for the economic sectors in distinct time scales. The results are as follows: (1) The "2-4 days" scale is the most risky scale, and the "8-16 days" scale is the least risky one. (2) The most influential and sensitive sectors are distinct in different time scales. (3) Although two sectors in the same community may not have direct spillover relations, the volatility of one sector will have a relatively strong influence on the other through indirect relations.

Cultures of choice: towards a sociology of choice as a cultural phenomenon.

PubMed

Schwarz, Ori

2017-09-07

The article explores different ways to conceptualize the relationship between choice and culture. These two notions are often constructed as opposites: while sociologies of modernization (such as Giddens') portray a shift from cultural traditions to culturally disembedded choice, dispositional sociologies (such as Bourdieu's) uncover cultural determination as the hidden truth behind apparent choice. However, choice may be real and cultural simultaneously. Culture moulds choice not only by inculcating dispositions or shaping repertoires of alternatives, but also by offering culturally specific choice practices, ways of choosing embedded in meaning, normativity, and materiality; and by shaping attributions of choice in everyday life. By bringing together insights from rival schools, I portray an outline for a comparative cultural sociology of choice, and demonstrate its purchase while discussing the digitalization of choice; and cultural logics that shape choice attribution in ways opposing neoliberal trends. © London School of Economics and Political Science 2017.

A Hybrid Computational Method for the Discovery of Novel Reproduction-Related Genes

PubMed Central

Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Guohua; Huang, Tao; Cai, Yu-Dong

2015-01-01

Uncovering the molecular mechanisms underlying reproduction is of great importance to infertility treatment and to the generation of healthy offspring. In this study, we discovered novel reproduction-related genes with a hybrid computational method, integrating three different types of method, which offered new clues for further reproduction research. This method was first executed on a weighted graph, constructed based on known protein-protein interactions, to search the shortest paths connecting any two known reproduction-related genes. Genes occurring in these paths were deemed to have a special relationship with reproduction. These newly discovered genes were filtered with a randomization test. Then, the remaining genes were further selected according to their associations with known reproduction-related genes measured by protein-protein interaction score and alignment score obtained by BLAST. The in-depth analysis of the high confidence novel reproduction genes revealed hidden mechanisms of reproduction and provided guidelines for further experimental validations. PMID:25768094

An investigation of social media data during a product recall scandal

NASA Astrophysics Data System (ADS)

Tse, Ying Kei; Loh, Hanlin; Ding, Juling; Zhang, Minhao

2018-07-01

As social media has become an important part of modern daily life, users often share product opinions online and these tend to spike when large companies undergo crises. This paper investigates customer online responses to a large company crisis by uncovering hidden insights in social media comments and presents a framework for handling social media data and crisis management. Analysis of textual Facebook data from users responding to the 2013 horsemeat scandal is presented. In this study, we used a novel comprehensive data analysis framework alongside a text-mining framework to objectively classify and understand customer perceptions during this horsemeat scandal. This framework provides an effective approach for investigating customer perception during a company crisis and measures the effectiveness of crisis management practices which the company has adopted. Our analyses show that social media can provide important insights into customer behaviour during crisis communications.

Reaction Mechanisms on Multiwell Potential Energy Surfaces in Combustion (and Atmospheric) Chemistry

DOE PAGES

Osborn, David L.

2017-03-15

Chemical reactions occurring on a potential energy surface with multiple wells are ubiquitous in low temperature combustion and the oxidation of volatile organic compounds in earth’s atmosphere. The rich variety of structural isomerizations that compete with collisional stabilization make characterizing such complex-forming reactions challenging. This review describes recent experimental and theoretical advances that deliver increasingly complete views of their reaction mechanisms. New methods for creating reactive intermediates coupled with multiplexed measurements provide many experimental observables simultaneously. Automated methods to explore potential energy surfaces can uncover hidden reactive pathways, while master equation methods enable a holistic treatment of both sequential andmore » well-skipping pathways. Our ability to probe and understand nonequilibrium effects and reaction sequences is increasing. These advances provide the fundamental science base for predictive models of combustion and the atmosphere that are crucial to address global challenges.« less

Revealing the hidden language of complex networks.

PubMed

Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Davis, Darren; Levnajic, Zoran; Janjic, Vuk; Karapandza, Rasa; Stojmirovic, Aleksandar; Pržulj, Nataša

2014-04-01

Sophisticated methods for analysing complex networks promise to be of great benefit to almost all scientific disciplines, yet they elude us. In this work, we make fundamental methodological advances to rectify this. We discover that the interaction between a small number of roles, played by nodes in a network, can characterize a network's structure and also provide a clear real-world interpretation. Given this insight, we develop a framework for analysing and comparing networks, which outperforms all existing ones. We demonstrate its strength by uncovering novel relationships between seemingly unrelated networks, such as Facebook, metabolic, and protein structure networks. We also use it to track the dynamics of the world trade network, showing that a country's role of a broker between non-trading countries indicates economic prosperity, whereas peripheral roles are associated with poverty. This result, though intuitive, has escaped all existing frameworks. Finally, our approach translates network topology into everyday language, bringing network analysis closer to domain scientists.

A hybrid computational method for the discovery of novel reproduction-related genes.

PubMed

Chen, Lei; Chu, Chen; Kong, Xiangyin; Huang, Guohua; Huang, Tao; Cai, Yu-Dong

2015-01-01

Uncovering the molecular mechanisms underlying reproduction is of great importance to infertility treatment and to the generation of healthy offspring. In this study, we discovered novel reproduction-related genes with a hybrid computational method, integrating three different types of method, which offered new clues for further reproduction research. This method was first executed on a weighted graph, constructed based on known protein-protein interactions, to search the shortest paths connecting any two known reproduction-related genes. Genes occurring in these paths were deemed to have a special relationship with reproduction. These newly discovered genes were filtered with a randomization test. Then, the remaining genes were further selected according to their associations with known reproduction-related genes measured by protein-protein interaction score and alignment score obtained by BLAST. The in-depth analysis of the high confidence novel reproduction genes revealed hidden mechanisms of reproduction and provided guidelines for further experimental validations.

Big Data Analytics for Genomic Medicine

PubMed Central

He, Karen Y.; Ge, Dongliang; He, Max M.

2017-01-01

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients’ genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs. PMID:28212287

Statistical significance of combinatorial regulations

PubMed Central

Terada, Aika; Okada-Hatakeyama, Mariko; Tsuda, Koji; Sese, Jun

2013-01-01

More than three transcription factors often work together to enable cells to respond to various signals. The detection of combinatorial regulation by multiple transcription factors, however, is not only computationally nontrivial but also extremely unlikely because of multiple testing correction. The exponential growth in the number of tests forces us to set a strict limit on the maximum arity. Here, we propose an efficient branch-and-bound algorithm called the “limitless arity multiple-testing procedure” (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists significant combinations without any limit, whereas the family-wise error rate is rigorously controlled under the threshold. In the human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in heterogeneous data. PMID:23882073

Reaction Mechanisms on Multiwell Potential Energy Surfaces in Combustion (and Atmospheric) Chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osborn, David L.

Chemical reactions occurring on a potential energy surface with multiple wells are ubiquitous in low temperature combustion and the oxidation of volatile organic compounds in earth’s atmosphere. The rich variety of structural isomerizations that compete with collisional stabilization make characterizing such complex-forming reactions challenging. This review describes recent experimental and theoretical advances that deliver increasingly complete views of their reaction mechanisms. New methods for creating reactive intermediates coupled with multiplexed measurements provide many experimental observables simultaneously. Automated methods to explore potential energy surfaces can uncover hidden reactive pathways, while master equation methods enable a holistic treatment of both sequential andmore » well-skipping pathways. Our ability to probe and understand nonequilibrium effects and reaction sequences is increasing. These advances provide the fundamental science base for predictive models of combustion and the atmosphere that are crucial to address global challenges.« less

Information Superiority via Formal Concept Analysis

NASA Astrophysics Data System (ADS)

Koester, Bjoern; Schmidt, Stefan E.

This chapter will show how to get more mileage out of information. To achieve that, we first start with an introduction to the fundamentals of Formal Concept Analysis (FCA). FCA is a highly versatile field of applied lattice theory, which allows hidden relationships to be uncovered in relational data. Moreover, FCA provides a distinguished supporting framework to subsequently find and fill information gaps in a systematic and rigorous way. In addition, we would like to build bridges via a universal approach to other communities which can be related to FCA in order for other research areas to benefit from a theory that has been elaborated for more than twenty years. Last but not least, the essential benefits of FCA will be presented algorithmically as well as theoretically by investigating a real data set from the MIPT Terrorism Knowledge Base and also by demonstrating an application in the field of Web Information Retrieval and Web Intelligence.

Coupling the Leidenfrost effect and elastic deformations to power sustained bouncing

NASA Astrophysics Data System (ADS)

Waitukaitis, Scott R.; Zuiderwijk, Antal; Souslov, Anton; Coulais, Corentin; van Hecke, Martin

2017-11-01

The Leidenfrost effect occurs when an object near a hot surface vaporizes rapidly enough to lift itself up and hover. Although well understood for liquids and stiff sublimable solids, nothing is known about the effect with materials whose stiffness lies between these extremes. Here we introduce a new phenomenon that occurs with vaporizable soft solids--the elastic Leidenfrost effect. By dropping hydrogel spheres onto hot surfaces we find that, rather than hovering, they energetically bounce several times their diameter for minutes at a time. With high-speed video during a single impact, we uncover high-frequency microscopic gap dynamics at the sphere/substrate interface. We show how these otherwise-hidden agitations constitute work cycles that harvest mechanical energy from the vapour and sustain the bouncing. Our findings suggest a new strategy for injecting mechanical energy into a widely used class of soft materials, with potential relevance to fields such as active matter, soft robotics and microfluidics.

Query-Based Outlier Detection in Heterogeneous Information Networks.

PubMed

Kuck, Jonathan; Zhuang, Honglei; Yan, Xifeng; Cam, Hasan; Han, Jiawei

2015-03-01

Outlier or anomaly detection in large data sets is a fundamental task in data science, with broad applications. However, in real data sets with high-dimensional space, most outliers are hidden in certain dimensional combinations and are relative to a user's search space and interest. It is often more effective to give power to users and allow them to specify outlier queries flexibly, and the system will then process such mining queries efficiently. In this study, we introduce the concept of query-based outlier in heterogeneous information networks, design a query language to facilitate users to specify such queries flexibly, define a good outlier measure in heterogeneous networks, and study how to process outlier queries efficiently in large data sets. Our experiments on real data sets show that following such a methodology, interesting outliers can be defined and uncovered flexibly and effectively in large heterogeneous networks.

Query-Based Outlier Detection in Heterogeneous Information Networks

PubMed Central

Kuck, Jonathan; Zhuang, Honglei; Yan, Xifeng; Cam, Hasan; Han, Jiawei

2015-01-01

Outlier or anomaly detection in large data sets is a fundamental task in data science, with broad applications. However, in real data sets with high-dimensional space, most outliers are hidden in certain dimensional combinations and are relative to a user’s search space and interest. It is often more effective to give power to users and allow them to specify outlier queries flexibly, and the system will then process such mining queries efficiently. In this study, we introduce the concept of query-based outlier in heterogeneous information networks, design a query language to facilitate users to specify such queries flexibly, define a good outlier measure in heterogeneous networks, and study how to process outlier queries efficiently in large data sets. Our experiments on real data sets show that following such a methodology, interesting outliers can be defined and uncovered flexibly and effectively in large heterogeneous networks. PMID:27064397

Uncovering temporal structure in hippocampal output patterns

PubMed Central

de Jong, Laurel Watkins; Pfeiffer, Brad E; Foster, David

2018-01-01

Place cell activity of hippocampal pyramidal cells has been described as the cognitive substrate of spatial memory. Replay is observed during hippocampal sharp-wave-ripple-associated population burst events (PBEs) and is critical for consolidation and recall-guided behaviors. PBE activity has historically been analyzed as a phenomenon subordinate to the place code. Here, we use hidden Markov models to study PBEs observed in rats during exploration of both linear mazes and open fields. We demonstrate that estimated models are consistent with a spatial map of the environment, and can even decode animals’ positions during behavior. Moreover, we demonstrate the model can be used to identify hippocampal replay without recourse to the place code, using only PBE model congruence. These results suggest that downstream regions may rely on PBEs to provide a substrate for memory. Additionally, by forming models independent of animal behavior, we lay the groundwork for studies of non-spatial memory. PMID:29869611

Uncovering temporal structure in hippocampal output patterns.

PubMed

Maboudi, Kourosh; Ackermann, Etienne; de Jong, Laurel Watkins; Pfeiffer, Brad E; Foster, David; Diba, Kamran; Kemere, Caleb

2018-06-05

Place cell activity of hippocampal pyramidal cells has been described as the cognitive substrate of spatial memory. Replay is observed during hippocampal sharp-wave-ripple-associated population burst events (PBEs) and is critical for consolidation and recall-guided behaviors. PBE activity has historically been analyzed as a phenomenon subordinate to the place code. Here, we use hidden Markov models to study PBEs observed in rats during exploration of both linear mazes and open fields. We demonstrate that estimated models are consistent with a spatial map of the environment, and can even decode animals' positions during behavior. Moreover, we demonstrate the model can be used to identify hippocampal replay without recourse to the place code, using only PBE model congruence. These results suggest that downstream regions may rely on PBEs to provide a substrate for memory. Additionally, by forming models independent of animal behavior, we lay the groundwork for studies of non-spatial memory. © 2018, Maboudi et al.

Improving Thin Bed Identification in Sarawak Basin Field using Short Time Fourier Transform Half Cepstrum (STFTHC) method

NASA Astrophysics Data System (ADS)

Nizarul, O.; Hermana, M.; Bashir, Y.; Ghosh, D. P.

2016-02-01

In delineating complex subsurface geological feature, broad band of frequencies are needed to unveil the often hidden features of hydrocarbon basin such as thin bedding. The ability to resolve thin geological horizon on seismic data is recognized to be a fundamental importance for hydrocarbon exploration, seismic interpretation and reserve prediction. For thin bedding, high frequency content is needed to enable tuning, which can be done by applying the band width extension technique. This paper shows an application of Short Time Fourier Transform Half Cepstrum (STFTHC) method, a frequency bandwidth expansion technique for non-stationary seismic signal in increasing the temporal resolution to uncover thin beds and improve characterization of the basin. A wedge model and synthetic seismic data is used to quantify the algorithm as well as real data from Sarawak basin were used to show the effectiveness of this method in enhancing the resolution.

Big Data Analytics for Genomic Medicine.

PubMed

He, Karen Y; Ge, Dongliang; He, Max M

2017-02-15

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients' genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.

Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding.

PubMed

Pechmann, Sebastian; Frydman, Judith

2013-02-01

The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to cotranslational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeast species, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate cotranslational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the cotranslational folding of corresponding polypeptides.

Understanding Road Usage Patterns in Urban Areas

NASA Astrophysics Data System (ADS)

Wang, Pu; Hunter, Timothy; Bayen, Alexandre M.; Schechtner, Katja; González, Marta C.

2012-12-01

In this paper, we combine the most complete record of daily mobility, based on large-scale mobile phone data, with detailed Geographic Information System (GIS) data, uncovering previously hidden patterns in urban road usage. We find that the major usage of each road segment can be traced to its own - surprisingly few - driver sources. Based on this finding we propose a network of road usage by defining a bipartite network framework, demonstrating that in contrast to traditional approaches, which define road importance solely by topological measures, the role of a road segment depends on both: its betweeness and its degree in the road usage network. Moreover, our ability to pinpoint the few driver sources contributing to the major traffic flow allows us to create a strategy that achieves a significant reduction of the travel time across the entire road system, compared to a benchmark approach.

Genetics of inherited cardiocutaneous syndromes: a review

PubMed Central

Bardawil, Tara; Khalil, Samar; Bergqvist, Christina; Abbas, Ossama; Kibbi, Abdul Ghani; Bitar, Fadi; Nemer, Georges; Kurban, Mazen

2016-01-01

The life of a human being originates as a single cell which, under the influence of certain factors, divides sequentially into multiple cells that subsequently become committed to develop and differentiate into the different structures and organs. Alterations occurring early on in the development process may lead to fetal demise in utero. Conversely, abnormalities at later stages may result in structural and/or functional abnormalities of varying severities. The cardiovascular system and skin share certain developmental and structural factors; therefore, it is not surprising to find several inherited syndromes with both cardiac and skin manifestations. Here, we will review the overlapping pathways in the development of the skin and heart, as well as the resulting syndromes. We will also highlight several cutaneous clues that may help physicians screen and uncover cardiac anomalies that may be otherwise hidden and result in sudden cardiac death. PMID:27933191

Maximal analytic extension and hidden symmetries of the dipole black ring

NASA Astrophysics Data System (ADS)

Armas, Jay

2011-12-01

We construct analytic extensions across the Killing horizons of non-extremal and extremal dipole black rings in Einstein-Maxwell’s theory using different methods. We show that these extensions are non-globally hyperbolic, have multiple asymptotically flat regions and, in the non-extremal case, are also maximal and timelike complete. Moreover, we find that in both cases, the causal structure of the maximally extended spacetime resembles that of the four-dimensional Reissner-Nordström black hole. Furthermore, motivated by the physical interpretation of one of these extensions, we find a separable solution to the Hamilton-Jacobi equation corresponding to zero energy null geodesics and relate it to the existence of a conformal Killing tensor and a conformal Killing-Yano tensor in a specific dimensionally reduced spacetime.

Predictive Rate-Distortion for Infinite-Order Markov Processes

NASA Astrophysics Data System (ADS)

Marzen, Sarah E.; Crutchfield, James P.

2016-06-01

Predictive rate-distortion analysis suffers from the curse of dimensionality: clustering arbitrarily long pasts to retain information about arbitrarily long futures requires resources that typically grow exponentially with length. The challenge is compounded for infinite-order Markov processes, since conditioning on finite sequences cannot capture all of their past dependencies. Spectral arguments confirm a popular intuition: algorithms that cluster finite-length sequences fail dramatically when the underlying process has long-range temporal correlations and can fail even for processes generated by finite-memory hidden Markov models. We circumvent the curse of dimensionality in rate-distortion analysis of finite- and infinite-order processes by casting predictive rate-distortion objective functions in terms of the forward- and reverse-time causal states of computational mechanics. Examples demonstrate that the resulting algorithms yield substantial improvements.

Viral Perturbations of Host Networks Reflect Disease Etiology

PubMed Central

Dricot, Amélie; Padi, Megha; Byrdsong, Danielle; Franchi, Rachel; Lee, Deok-Sun; Rozenblatt-Rosen, Orit; Mar, Jessica C.; Calderwood, Michael A.; Baldwin, Amy; Zhao, Bo; Santhanam, Balaji; Braun, Pascal; Simonis, Nicolas; Huh, Kyung-Won; Hellner, Karin; Grace, Miranda; Chen, Alyce; Rubio, Renee; Marto, Jarrod A.; Christakis, Nicholas A.; Kieff, Elliott; Roth, Frederick P.; Roecklein-Canfield, Jennifer; DeCaprio, James A.; Cusick, Michael E.; Quackenbush, John; Hill, David E.; Münger, Karl; Vidal, Marc; Barabási, Albert-László

2012-01-01

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia. PMID:22761553

[An epidemiological but invisibilized marker: indebtedness within an Afromexican town in Oaxaca].

PubMed

Hersch-Martínez, Paul; Rodríguez-Hernández, Berenice

2017-01-01

To explore indebtedness dynamics in an Afromexican town by an inclusive epidemiological approach. Qualitative study through 75 questionnaires, 20 interviews to depth and six focal groups in a support process to the Municipal Health Commission in Santiago Tapextla, Oaxaca. Catastrophic expenses due to insufficient medical care were the principal causal item. Indebtedness processes with patrimonial loss are dominant, generating dependence spirals of difficult resolution that impact the familiar dynamics and the pathology evolution. In spite of its inexistence within sanitary official programs, indebtedness dynamics constitute an epidemiological marker by the uncovering of structural inattention conditions that reflect the imposed, naturalized and pathogenic hierarchization proper of coloniality. To analyze this process at local and global levels is a complex but essential public health task.

The efficacy of student-centered instruction in supporting science learning.

PubMed

Granger, E M; Bevis, T H; Saka, Y; Southerland, S A; Sampson, V; Tate, R L

2012-10-05

Transforming science learning through student-centered instruction that engages students in a variety of scientific practices is central to national science-teaching reform efforts. Our study employed a large-scale, randomized-cluster experimental design to compare the effects of student-centered and teacher-centered approaches on elementary school students' understanding of space-science concepts. Data included measures of student characteristics and learning and teacher characteristics and fidelity to the instructional approach. Results reveal that learning outcomes were higher for students enrolled in classrooms engaging in scientific practices through a student-centered approach; two moderators were identified. A statistical search for potential causal mechanisms for the observed outcomes uncovered two potential mediators: students' understanding of models and evidence and the self-efficacy of teachers.

Improving the Quality of Alerts and Predicting Intruder's Next Goal with Hidden Colored Petri-Net

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Dong; Frincke, Deb A.

2006-06-22

Intrusion detection systems (IDS) often provide poor quality alerts, which are insufficient to support rapid identification of ongoing attacks or predict an intruder’s next likely goal. In this paper, we propose a novel approach to alert post-processing and correlation, the Hidden Colored Petri-Net (HCPN). Different from most other alert correlation methods, our approach treats the alert correlation problem as an inference problem rather than a filter problem. Our approach assumes that the intruder’s actions are unknown to the IDS and can be inferred only from the alerts generated by the IDS sensors. HCPN can describe the relationship between different stepsmore » carried out by intruders, model observations (alerts) and transitions (actions) separately, and associate each token element (system state) with a probability (or confidence). The model is an extension to Colored Petri-Net (CPN) .It is so called “hidden” because the transitions (actions) are not directly observable but can be inferred by looking through the observations (alerts). These features make HCPN especially suitable for discovering intruders’ actions from their partial observations (alerts,) and predicting intruders’ next goal. Our experiments on DARPA evaluation datasets and the attack scenarios from the Grand Challenge Problem (GCP) show that HCPN has promise as a way to reducing false positives and negatives, predicting intruder’s next possible action, uncovering intruders’ intrusion strategies after the attack scenario has happened, and providing confidence scores.« less

Global hidden harvest of freshwater fish revealed by household surveys.

PubMed

Fluet-Chouinard, Etienne; Funge-Smith, Simon; McIntyre, Peter B

2018-06-18

Consumption of wild-caught freshwater fish is concentrated in low-income countries, where it makes a critical contribution to food security and livelihoods. Underestimation of inland harvests in official statistics has long been suspected due to unmonitored subsistence fisheries. To overcome the lack of data from extensive small-scale harvests, we used household consumption surveys to estimate freshwater fish catches in 42 low- and middle-income countries between 1997 and 2014. After accounting for trade and aquaculture, these countries collectively consumed 3.6 MT (CI, 1.5-5.8) more wild-caught freshwater fish than officially reported, reflecting a net underreporting of 64.8% (CI, 27.1-103.9%). Individual countries were more likely to underestimate ( n = 31) than overestimate ( n = 11) catches, despite conservative assumptions in our calculations. Extrapolating our findings suggests that the global inland catch reported as 10.3 MT in 2008 was more likely 16.6 MT (CI, 2.3-30.9), which accords with recent independent predictions for rivers and lakes. In human terms, these hidden harvests are equivalent to the total animal protein consumption of 36.9 (CI, 30.8-43.4) million people, including many who rely upon wild fish to achieve even minimal protein intake. The widespread underreporting uncovered by household consumption surveys indicates that inland fisheries contribute far more to global food security than has been recognized previously. Our findings also amplify concerns about the sustainability of intensive fishery exploitation as degradation of rivers, lakes, and wetlands continues apace.

Humanoid infers Archimedes' principle: understanding physical relations and object affordances through cumulative learning experiences

PubMed Central

2016-01-01

Emerging studies indicate that several species such as corvids, apes and children solve ‘The Crow and the Pitcher’ task (from Aesop's Fables) in diverse conditions. Hidden beneath this fascinating paradigm is a fundamental question: by cumulatively interacting with different objects, how can an agent abstract the underlying cause–effect relations to predict and creatively exploit potential affordances of novel objects in the context of sought goals? Re-enacting this Aesop's Fable task on a humanoid within an open-ended ‘learning–prediction–abstraction’ loop, we address this problem and (i) present a brain-guided neural framework that emulates rapid one-shot encoding of ongoing experiences into a long-term memory and (ii) propose four task-agnostic learning rules (elimination, growth, uncertainty and status quo) that correlate predictions from remembered past experiences with the unfolding present situation to gradually abstract the underlying causal relations. Driven by the proposed architecture, the ensuing robot behaviours illustrated causal learning and anticipation similar to natural agents. Results further demonstrate that by cumulatively interacting with few objects, the predictions of the robot in case of novel objects converge close to the physical law, i.e. the Archimedes principle: this being independent of both the objects explored during learning and the order of their cumulative exploration. PMID:27466440

Humanoid infers Archimedes' principle: understanding physical relations and object affordances through cumulative learning experiences.

PubMed

Bhat, Ajaz Ahmad; Mohan, Vishwanathan; Sandini, Giulio; Morasso, Pietro

2016-07-01

Emerging studies indicate that several species such as corvids, apes and children solve 'The Crow and the Pitcher' task (from Aesop's Fables) in diverse conditions. Hidden beneath this fascinating paradigm is a fundamental question: by cumulatively interacting with different objects, how can an agent abstract the underlying cause-effect relations to predict and creatively exploit potential affordances of novel objects in the context of sought goals? Re-enacting this Aesop's Fable task on a humanoid within an open-ended 'learning-prediction-abstraction' loop, we address this problem and (i) present a brain-guided neural framework that emulates rapid one-shot encoding of ongoing experiences into a long-term memory and (ii) propose four task-agnostic learning rules (elimination, growth, uncertainty and status quo) that correlate predictions from remembered past experiences with the unfolding present situation to gradually abstract the underlying causal relations. Driven by the proposed architecture, the ensuing robot behaviours illustrated causal learning and anticipation similar to natural agents. Results further demonstrate that by cumulatively interacting with few objects, the predictions of the robot in case of novel objects converge close to the physical law, i.e. the Archimedes principle: this being independent of both the objects explored during learning and the order of their cumulative exploration. © 2016 The Author(s).

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

PubMed

Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

2016-02-01

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Causal assessment of occupational pushing or pulling and low back pain: results of a systematic review.

PubMed

Roffey, Darren M; Wai, Eugene K; Bishop, Paul; Kwon, Brian K; Dagenais, Simon

2010-06-01

Low back pain (LBP) is a prevalent and expensive musculoskeletal condition that predominantly occurs in working-age individuals of industrialized nations. Although numerous occupational physical activities have been implicated in its etiology, determining the causation of occupational LBP still remains a challenge. To conduct a systematic review evaluating the causal relationship between occupational pushing or pulling and LBP. Systematic review of the literature. Studies reporting an association between occupational pushing or pulling and LBP. Numerical association between exposure to pushing or pulling and the presence of LBP. A systematic review was performed to identify, evaluate, and summarize the literature related to establishing a causal relationship, according to Bradford-Hill criteria for causation for occupational pushing or pulling and LBP. A search was conducted using Medline, EMBASE, CINAHL, Cochrane Library, and OSH-ROM, gray literature, hand-searching occupational health journals, reference lists of included studies, and expert knowledge. Methodological quality was assessed using a modified Newcastle-Ottawa Scale. This search yielded 2,766 citations. Thirteen studies met the inclusion criteria. Eight were high-quality studies and five were low-quality studies. There was conflicting evidence with one high-quality study demonstrating a positive association between occupational pushing or pulling and LBP and five studies showing no relationship. One study reported a nonstatistically significant dose-response trend, four studies discussed temporality of which one indicated a positive finding, two studies discussed the biological plausibility of a causal link between occupational pushing or pulling and LBP, and no evidence was uncovered to assess the experiment criterion. A qualitative summary of existing studies was not able to find any high-quality studies that fully satisfied any of the Bradford-Hill causation criteria for occupational pushing or pulling and LBP. Based on the evidence reviewed, it is unlikely that occupational pushing or pulling is independently causative of LBP in the populations of workers studied. Copyright 2010 Elsevier Inc. All rights reserved.

Graph pyramids for protein function prediction

PubMed Central

2015-01-01

Background Uncovering the hidden organizational characteristics and regularities among biological sequences is the key issue for detailed understanding of an underlying biological phenomenon. Thus pattern recognition from nucleic acid sequences is an important affair for protein function prediction. As proteins from the same family exhibit similar characteristics, homology based approaches predict protein functions via protein classification. But conventional classification approaches mostly rely on the global features by considering only strong protein similarity matches. This leads to significant loss of prediction accuracy. Methods Here we construct the Protein-Protein Similarity (PPS) network, which captures the subtle properties of protein families. The proposed method considers the local as well as the global features, by examining the interactions among 'weakly interacting proteins' in the PPS network and by using hierarchical graph analysis via the graph pyramid. Different underlying properties of the protein families are uncovered by operating the proposed graph based features at various pyramid levels. Results Experimental results on benchmark data sets show that the proposed hierarchical voting algorithm using graph pyramid helps to improve computational efficiency as well the protein classification accuracy. Quantitatively, among 14,086 test sequences, on an average the proposed method misclassified only 21.1 sequences whereas baseline BLAST score based global feature matching method misclassified 362.9 sequences. With each correctly classified test sequence, the fast incremental learning ability of the proposed method further enhances the training model. Thus it has achieved more than 96% protein classification accuracy using only 20% per class training data. PMID:26044522

Graph pyramids for protein function prediction.

PubMed

Sandhan, Tushar; Yoo, Youngjun; Choi, Jin; Kim, Sun

2015-01-01

Uncovering the hidden organizational characteristics and regularities among biological sequences is the key issue for detailed understanding of an underlying biological phenomenon. Thus pattern recognition from nucleic acid sequences is an important affair for protein function prediction. As proteins from the same family exhibit similar characteristics, homology based approaches predict protein functions via protein classification. But conventional classification approaches mostly rely on the global features by considering only strong protein similarity matches. This leads to significant loss of prediction accuracy. Here we construct the Protein-Protein Similarity (PPS) network, which captures the subtle properties of protein families. The proposed method considers the local as well as the global features, by examining the interactions among 'weakly interacting proteins' in the PPS network and by using hierarchical graph analysis via the graph pyramid. Different underlying properties of the protein families are uncovered by operating the proposed graph based features at various pyramid levels. Experimental results on benchmark data sets show that the proposed hierarchical voting algorithm using graph pyramid helps to improve computational efficiency as well the protein classification accuracy. Quantitatively, among 14,086 test sequences, on an average the proposed method misclassified only 21.1 sequences whereas baseline BLAST score based global feature matching method misclassified 362.9 sequences. With each correctly classified test sequence, the fast incremental learning ability of the proposed method further enhances the training model. Thus it has achieved more than 96% protein classification accuracy using only 20% per class training data.

From Matter to Life

NASA Astrophysics Data System (ADS)

Imari Walker, Sara; Davies, Paul C. W.; Ellis, George F. R.

2017-02-01

1. Introduction Sara Imari Walker, Paul C. W. Davies and F. R. Ellis; Part I. Physics and Life: 2. The 'hard problem' of life Sara Imari Walker and Paul C. W. Davies; 3. Beyond initial conditions and laws of motion: constructor theory of information and life Chiara Marletto; Part II. Bio from Bit: 4. (How) did information emerge? Anne-Marie Grisogono; 5. On the emerging codes for chemical evolution Jillian E. Smith-Carpenter, Sha Li, Jay T. Goodwin, Anil K. Mehta and David G. Lynn; 6. Digital and analogue information in organisms Denis Noble; 7. From entropy to information: biased typewriters and the origin of life Christoph Adami and Thomas Labar; Part III. Life's Hidden Information: 8. Cryptographic nature David Krakauer; 9. Noise and function Steven Weinstein and Theodore Pavlic; 10. The many faces of state space compression David Wolpert, Eric Libby, Joshua Grochow and Simon DeDeo; 11. Causality, information and biological computation: an algorithmic software approach to life, disease and the immune system Hector Zenil, Angelika Schmidt and Jesper Tegnér; Part IV. Complexity and Causality: 12. Life's information hierarchy Jessica Flack; 13. Living through downward causation: from molecules to ecosystems Keith D. Farnsworth, George F. R. Ellis and Luc Jaeger; 14. Automata and animats: from dynamics to cause-effect structures Larissa Albantakis and Giulio Tononi; 15. Biological information, causality and specificity - an intimate relationship Karola Stotz and Paul Griffiths; Part V. From Matter to Mind: 16. Major transitions in political order Simon DeDeo; 17. Bits from biology for computational intelligence Michael Wibral, Joseph Lizier and Viola Priesemann; 18. Machine learning and the questions it raises G. Andrew D. Briggs and Dawid Potgieter.

Nonlocality of the original Einstein-Podolsky-Rosen state

NASA Astrophysics Data System (ADS)

Cohen, O.

1997-11-01

We examine the properties and behavior of the original Einstein-Podolsky-Rosen (EPR) wave function [Phys. Rev. 47, 777 (1935)] and related Gaussian-correlated wave functions. We assess the degree of entanglement of these wave functions and consider an argument of Bell [Ann. (N.Y.) Acad. Sci. 480, 263 (1986)] based on the Wigner phase-space distribution [Phys. Rev. 40, 749 (1932)], which implies that the original EPR correlations can accommodate a local hidden-variable description. We extend Bell's analysis to the related Gaussian wave functions. We then show that it is possible to identify definite nonlocal aspects for the original EPR state and related states. We describe possible experiments that would demonstrate these nonlocal features through violations of Bell inequalities. The implications of our results, and in particular their relevance for the causal interpretation of quantum mechanics, are considered.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

PubMed

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-04-01

Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. Copyright © 2016 White et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

PubMed Central

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-01-01

Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. Funding UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. PMID:26781229

THE EDUCATION-HEALTH GRADIENT.

PubMed

Conti, Gabriella; Heckman, James; Urzua, Sergio

2010-05-01

In this paper, we determine the role played by early cognitive, noncognitive, and health endowments. We identify the causal effect of education on health and health-related behaviors. We develop an empirical model of schooling choice and post-schooling outcomes, where both schooling and the outcomes determined in part by schooling are influenced by measured early family environments and latent capabilities (cognitive, noncognitive and health). We show that family background characteristics, and cognitive, noncognitive, and health endowments developed by age 10, are important determinants of labor market and health disparities at age 30. Not properly accounting for personality traits overestimates the importance of cognitive ability in determining adult health. Selection on factors determined early in life explains more than half of the observed difference by education in poor health, depression, and obesity. Education has an important causal effect in explaining differences in many adult outcomes and healthy behaviors. We uncover significant gender differences. We go beyond the current literature which typically estimates mean effects to compute distributions of treatment effects. We show how the health returns to education can vary among individuals who are similar with respect to their observed characteristics, and how a mean effect can hide gains and losses for different individuals. Our research highlights the important role played by the early years in producing health.

A Spectroscopic Search for White Dwarf Companions to 101 Nearby M Dwarfs

NASA Astrophysics Data System (ADS)

Bar, Ira; Vreeswijk, Paul; Gal-Yam, Avishay; Ofek, Eran O.; Nelemans, Gijs

2017-11-01

Recent studies of the stellar population in the solar neighborhood (<20 pc) suggest that there are undetected white dwarfs (WDs) in multiple systems with main-sequence companions. Detecting these hidden stars and obtaining a more complete census of nearby WDs is important for our understanding of stellar and galactic evolution, as well as the study of explosive phenomena. In an attempt to uncover these hidden WDs, we present intermediate resolution spectroscopy over the wavelength range of 3000-25000 Å of 101 nearby M dwarfs (dMs), observed with the Very Large Telescope X-Shooter spectrograph. For each star we search for a hot component superimposed on the dM spectrum. X-Shooter has excellent blue sensitivity and thus can reveal a faint hot WD despite the brightness of its red companion. Visual examination shows no clear evidence of a WD in any of the spectra. We place upper limits on the effective temperatures of WDs that may still be hiding by fitting dM templates to the spectra and modeling the WD spectra. On average our survey is sensitive to WDs hotter than about 5300 K. This suggests that the frequency of WD companions of {T}{eff}≳ 5300 {{K}} with separation of the order of ≲50 au among the local dM population is <3% at the 95% confidence level. The reduced spectra are made available via the WISeREP3 repository. Based on observations collected in service mode using the Very Large Telescope (VLT) under program IDs 095_D-0949(A) and 096_D-0963(A).

A comparative hidden Markov model analysis pipeline identifies proteins characteristic of cereal-infecting fungi

PubMed Central

2013-01-01

Background Fungal pathogens cause devastating losses in economically important cereal crops by utilising pathogen proteins to infect host plants. Secreted pathogen proteins are referred to as effectors and have thus far been identified by selecting small, cysteine-rich peptides from the secretome despite increasing evidence that not all effectors share these attributes. Results We take advantage of the availability of sequenced fungal genomes and present an unbiased method for finding putative pathogen proteins and secreted effectors in a query genome via comparative hidden Markov model analyses followed by unsupervised protein clustering. Our method returns experimentally validated fungal effectors in Stagonospora nodorum and Fusarium oxysporum as well as the N-terminal Y/F/WxC-motif from the barley powdery mildew pathogen. Application to the cereal pathogen Fusarium graminearum reveals a secreted phosphorylcholine phosphatase that is characteristic of hemibiotrophic and necrotrophic cereal pathogens and shares an ancient selection process with bacterial plant pathogens. Three F. graminearum protein clusters are found with an enriched secretion signal. One of these putative effector clusters contains proteins that share a [SG]-P-C-[KR]-P sequence motif in the N-terminal and show features not commonly associated with fungal effectors. This motif is conserved in secreted pathogenic Fusarium proteins and a prime candidate for functional testing. Conclusions Our pipeline has successfully uncovered conservation patterns, putative effectors and motifs of fungal pathogens that would have been overlooked by existing approaches that identify effectors as small, secreted, cysteine-rich peptides. It can be applied to any pathogenic proteome data, such as microbial pathogen data of plants and other organisms. PMID:24252298

Secreted glyceraldehye-3-phosphate dehydrogenase is a multifunctional autocrine transferrin receptor for cellular iron acquisition.

PubMed

Sheokand, Navdeep; Kumar, Santosh; Malhotra, Himanshu; Tillu, Vikas; Raje, Chaaya Iyengar; Raje, Manoj

2013-06-01

The long held view is that mammalian cells obtain transferrin (Tf) bound iron utilizing specialized membrane anchored receptors. Here we report that, during increased iron demand, cells secrete the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which enhances cellular uptake of Tf and iron. These observations could be mimicked by utilizing purified GAPDH injected into mice as well as when supplemented in culture medium of model cell lines and primary cell types that play a key role in iron metabolism. Transferrin and iron delivery was evaluated by biochemical, biophysical and imaging based assays. This mode of iron uptake is a saturable, energy dependent pathway, utilizing raft as well as non-raft domains of the cell membrane and also involves the membrane protein CD87 (uPAR). Tf internalized by this mode is also catabolized. Our research demonstrates that, even in cell types that express the known surface receptor based mechanism for transferrin uptake, more transferrin is delivered by this route which represents a hidden dimension of iron homeostasis. Iron is an essential trace metal for practically all living organisms however its acquisition presents major challenges. The current paradigm is that living organisms have developed well orchestrated and evolved mechanisms involving iron carrier molecules and their specific receptors to regulate its absorption, transport, storage and mobilization. Our research uncovers a hidden and primitive pathway of bulk iron trafficking involving a secreted receptor that is a multifunctional glycolytic enzyme that has implications in pathological conditions such as infectious diseases and cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

Spontaneous Symmetry Breaking as a Basis of Particle Mass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quigg, Chris; /Fermilab /CERN

2007-04-01

Electroweak theory joins electromagnetism with the weak force in a single quantum field theory, ascribing the two fundamental interactions--so different in their manifestations--to a common symmetry principle. How the electroweak gauge symmetry is hidden is one of the most urgent and challenging questions facing particle physics. The provisional answer incorporated in the ''standard model'' of particle physics was formulated in the 1960s by Higgs, by Brout & Englert, and by Guralnik, Hagen, & Kibble: The agent of electroweak symmetry breaking is an elementary scalar field whose self-interactions select a vacuum state in which the full electroweak symmetry is hidden, leavingmore » a residual phase symmetry of electromagnetism. By analogy with the Meissner effect of the superconducting phase transition, the Higgs mechanism, as it is commonly known, confers masses on the weak force carriers W{sup {+-}} and Z. It also opens the door to masses for the quarks and leptons, and shapes the world around us. It is a good story--though an incomplete story--and we do not know how much of the story is true. Experiments that explore the Fermi scale (the energy regime around 1 TeV) during the next decade will put the electroweak theory to decisive test, and may uncover new elements needed to construct a more satisfying completion of the electroweak theory. The aim of this article is to set the stage by reporting what we know and what we need to know, and to set some ''Big Questions'' that will guide our explorations.« less

Dynamic causal modelling of brain-behaviour relationships.

PubMed

Rigoux, L; Daunizeau, J

2015-08-15

In this work, we expose a mathematical treatment of brain-behaviour relationships, which we coin behavioural Dynamic Causal Modelling or bDCM. This approach aims at decomposing the brain's transformation of stimuli into behavioural outcomes, in terms of the relative contribution of brain regions and their connections. In brief, bDCM places the brain at the interplay between stimulus and behaviour: behavioural outcomes arise from coordinated activity in (hidden) neural networks, whose dynamics are driven by experimental inputs. Estimating neural parameters that control network connectivity and plasticity effectively performs a neurobiologically-constrained approximation to the brain's input-outcome transform. In other words, neuroimaging data essentially serves to enforce the realism of bDCM's decomposition of input-output relationships. In addition, post-hoc artificial lesions analyses allow us to predict induced behavioural deficits and quantify the importance of network features for funnelling input-output relationships. This is important, because this enables one to bridge the gap with neuropsychological studies of brain-damaged patients. We demonstrate the face validity of the approach using Monte-Carlo simulations, and its predictive validity using empirical fMRI/behavioural data from an inhibitory control task. Lastly, we discuss promising applications of this work, including the assessment of functional degeneracy (in the healthy brain) and the prediction of functional recovery after lesions (in neurological patients). Copyright © 2015 Elsevier Inc. All rights reserved.

Exposing the dark sector with future Z factories

NASA Astrophysics Data System (ADS)

Liu, Jia; Wang, Lian-Tao; Wang, Xiao-Ping; Xue, Wei

2018-05-01

We investigate the prospects of searching dark sector models via exotic Z -boson decay at future e+e- colliders with Giga Z and Tera Z options. Four general categories of dark sector models, Higgs portal dark matter, vector-portal dark matter, inelastic dark matter, and axionlike particles, are considered. Focusing on channels motivated by the dark sector models, we carry out a model-independent study of the sensitivities of Z factories in probing exotic decays. The limits on branching ratios of the exotic Z decay are typically O (10-6- 10-8.5) for the Giga Z and O (10-7.5- 10-11) for the Tera Z , and they are compared with the projection for the high luminosity LHC. We demonstrate that future Z factories can provide its unique and leading sensitivity and highlight the complementarity with other experiments, including the indirect and direct dark matter search limits and the existing collider limits. Future Z factories will play a leading role in uncovering the hidden sector of the Universe in the future.

[A unit for emergency psychiatry and crisis intervention--concepts, structure and initial experiences].

PubMed

Feuerlein, W; Bronisch, T; Fürmaier, A

1983-03-01

The article reports on a ward with 12 beds which has been set up for emergency cases in psychiatry or for immediate intervention in case of a crisis experienced by a patient. In the theoretical part of this article, it is explained that crisis situations are present in most of the psychiatric emergency patients. The article then goes briefly into the fundamentals of therapeutic strategy in such patients: A therapy which helps to uncover hidden conflicts, the pros and cons of therapy focussed on conflict and on supportive measures; as well as a therapy which supports and promotes the ego. This is followed by a comparison of the ward with corresponding facilities in Germany and abroad and a description of their structure, their patients and their function within a psychiatric care system. The concluding part of the article is devoted to a description of the authors' initial experiences and impressions gained during their work with the ward patients, quoting several examples.

Digitizing mass spectrometry data to explore the chemical diversity and distribution of marine cyanobacteria and algae

PubMed Central

Luzzatto-Knaan, Tal; Garg, Neha; Wang, Mingxun; Glukhov, Evgenia; Peng, Yao; Ackermann, Gail; Amir, Amnon; Duggan, Brendan M; Ryazanov, Sergey; Gerwick, Lena; Knight, Rob; Alexandrov, Theodore; Bandeira, Nuno; Gerwick, William H; Dorrestein, Pieter C

2017-01-01

Natural product screening programs have uncovered molecules from diverse natural sources with various biological activities and unique structures. However, much is yet underexplored and additional information is hidden in these exceptional collections. We applied untargeted mass spectrometry approaches to capture the chemical space and dispersal patterns of metabolites from an in-house library of marine cyanobacterial and algal collections. Remarkably, 86% of the metabolomics signals detected were not found in other available datasets of similar nature, supporting the hypothesis that marine cyanobacteria and algae possess distinctive metabolomes. The data were plotted onto a world map representing eight major sampling sites, and revealed potential geographic locations with high chemical diversity. We demonstrate the use of these inventories as a tool to explore the diversity and distribution of natural products. Finally, we utilized this tool to guide the isolation of a new cyclic lipopeptide, yuvalamide A, from a marine cyanobacterium. DOI: http://dx.doi.org/10.7554/eLife.24214.001 PMID:28492366

An Annotation Agnostic Algorithm for Detecting Nascent RNA Transcripts in GRO-Seq.

PubMed

Azofeifa, Joseph G; Allen, Mary A; Lladser, Manuel E; Dowell, Robin D

2017-01-01

We present a fast and simple algorithm to detect nascent RNA transcription in global nuclear run-on sequencing (GRO-seq). GRO-seq is a relatively new protocol that captures nascent transcripts from actively engaged polymerase, providing a direct read-out on bona fide transcription. Most traditional assays, such as RNA-seq, measure steady state RNA levels which are affected by transcription, post-transcriptional processing, and RNA stability. GRO-seq data, however, presents unique analysis challenges that are only beginning to be addressed. Here, we describe a new algorithm, Fast Read Stitcher (FStitch), that takes advantage of two popular machine-learning techniques, hidden Markov models and logistic regression, to classify which regions of the genome are transcribed. Given a small user-defined training set, our algorithm is accurate, robust to varying read depth, annotation agnostic, and fast. Analysis of GRO-seq data without a priori need for annotation uncovers surprising new insights into several aspects of the transcription process.

Large area optical mapping of surface contact angle.

PubMed

Dutra, Guilherme; Canning, John; Padden, Whayne; Martelli, Cicero; Dligatch, Svetlana

2017-09-04

Top-down contact angle measurements have been validated and confirmed to be as good if not more reliable than side-based measurements. A range of samples, including industrially relevant materials for roofing and printing, has been compared. Using the top-down approach, mapping in both 1-D and 2-D has been demonstrated. The method was applied to study the change in contact angle as a function of change in silver (Ag) nanoparticle size controlled by thermal evaporation. Large area mapping reveals good uniformity for commercial Aspen paper coated with black laser printer ink. A demonstration of the forensic and chemical analysis potential in 2-D is shown by uncovering the hidden CsF initials made with mineral oil on the coated Aspen paper. The method promises to revolutionize nanoscale characterization and industrial monitoring as well as chemical analyses by allowing rapid contact angle measurements over large areas or large numbers of samples in ways and times that have not been possible before.

Igloo-Plot: a tool for visualization of multidimensional datasets.

PubMed

Kuntal, Bhusan K; Ghosh, Tarini Shankar; Mande, Sharmila S

2014-01-01

Advances in science and technology have resulted in an exponential growth of multivariate (or multi-dimensional) datasets which are being generated from various research areas especially in the domain of biological sciences. Visualization and analysis of such data (with the objective of uncovering the hidden patterns therein) is an important and challenging task. We present a tool, called Igloo-Plot, for efficient visualization of multidimensional datasets. The tool addresses some of the key limitations of contemporary multivariate visualization and analysis tools. The visualization layout, not only facilitates an easy identification of clusters of data-points having similar feature compositions, but also the 'marker features' specific to each of these clusters. The applicability of the various functionalities implemented herein is demonstrated using several well studied multi-dimensional datasets. Igloo-Plot is expected to be a valuable resource for researchers working in multivariate data mining studies. Igloo-Plot is available for download from: http://metagenomics.atc.tcs.com/IglooPlot/. Copyright © 2014 Elsevier Inc. All rights reserved.

Self-made shelters protect spiders from predation

PubMed Central

Manicom, Carryn; Schwarzkopf, Lin; Alford, Ross A.; Schoener, Thomas W.

2008-01-01

Many animals modify their environments, apparently to reduce predation risk, but the success of such endeavors, and their impact on the density and distribution of populations, are rarely rigorously demonstrated. We staged a manipulative experiment to assess the effectiveness of self-made shelters by web spiders as protection from natural enemies. Scincid lizards were included or excluded from 21 replicated 200-m2 plots, and spiders therein were classified as exposed or sheltered, depending on whether they were uncovered in their web or hidden in cocoons, leaves/debris, or burrows. We found that exposed spiders were greatly affected by the presence of predatory scincid lizards, whereas sheltered spiders were not. More specifically, lizards, which forage close to the ground, reduced the abundance of exposed spiders by two-thirds but had no effect on the abundance of sheltered spiders. Sheltered spiders were able to avoid predation and share space with lizards, suggesting that shelter construction is a mechanism for reducing predation risk and has important population consequences. PMID:18772383

Two New Species of Bibloplectus Reitter (Coleoptera: Staphylinidae: Pselaphinae) from the Orlando Park Collection, Field Museum of Natural History.

PubMed

Owens, Brittany E; Carlton, Christopher E

2018-04-10

Two new species of Bibloplectus Reitter, 1881 are described from the Orlando Park Collection of Pselaphinae at the FMNH (Field Museum of Natural History, Chicago, IL, USA): Bibloplectus silvestris Owens and Carlton, new species (type locality, Urbana, IL, USA) and Bibloplectus wingi Owens and Carlton, new species (type locality, Shades State Park, IN, USA). Types of these new species were part of a series of specimens bearing unpublished Park manuscript names in both the pinned and slide collection at the FMNH. They bring the total number of species in the genus in eastern North America to twenty-three. Resolving these manuscript names adds to previous efforts to uncover elements of the hidden diversity of North American Bibloplectus from museum collections (Owens and Carlton 2016, Owens and Carlton 2017) and highlights the importance of close examination of the Orlando Park pselaphine collection as a valuable historic and taxonomic resource.

Revealing the Hidden Language of Complex Networks

PubMed Central

Yaveroğlu, Ömer Nebil; Malod-Dognin, Noël; Davis, Darren; Levnajic, Zoran; Janjic, Vuk; Karapandza, Rasa; Stojmirovic, Aleksandar; Pržulj, Nataša

2014-01-01

Sophisticated methods for analysing complex networks promise to be of great benefit to almost all scientific disciplines, yet they elude us. In this work, we make fundamental methodological advances to rectify this. We discover that the interaction between a small number of roles, played by nodes in a network, can characterize a network's structure and also provide a clear real-world interpretation. Given this insight, we develop a framework for analysing and comparing networks, which outperforms all existing ones. We demonstrate its strength by uncovering novel relationships between seemingly unrelated networks, such as Facebook, metabolic, and protein structure networks. We also use it to track the dynamics of the world trade network, showing that a country's role of a broker between non-trading countries indicates economic prosperity, whereas peripheral roles are associated with poverty. This result, though intuitive, has escaped all existing frameworks. Finally, our approach translates network topology into everyday language, bringing network analysis closer to domain scientists. PMID:24686408

Biphasic responses in multi-site phosphorylation systems.

PubMed

Suwanmajo, Thapanar; Krishnan, J

2013-12-06

Multi-site phosphorylation systems are repeatedly encountered in cellular biology and multi-site modification is a basic building block of post-translational modification. In this paper, we demonstrate how distributive multi-site modification mechanisms by a single kinase/phosphatase pair can lead to biphasic/partial biphasic dose-response characteristics for the maximally phosphorylated substrate at steady state. We use simulations and analysis to uncover a hidden competing effect which is responsible for this and analyse how it may be accentuated. We build on this to analyse different variants of multi-site phosphorylation mechanisms showing that some mechanisms are intrinsically not capable of displaying this behaviour. This provides both a consolidated understanding of how and under what conditions biphasic responses are obtained in multi-site phosphorylation and a basis for discriminating between different mechanisms based on this. We also demonstrate how this behaviour may be combined with other behaviour such as threshold and bistable responses, demonstrating the capacity of multi-site phosphorylation systems to act as complex molecular signal processors.

Quantum confinement effect in 6H-SiC quantum dots observed via plasmon-exciton coupling-induced defect-luminescence quenching

NASA Astrophysics Data System (ADS)

Guo, Xiaoxiao; Zhang, Yumeng; Fan, Baolu; Fan, Jiyang

2017-03-01

The quantum confinement effect is one of the crucial physical effects that discriminate a quantum material from its bulk material. It remains a mystery why the 6H-SiC quantum dots (QDs) do not exhibit an obvious quantum confinement effect. We study the photoluminescence of the coupled colloidal system of SiC QDs and Ag nanoparticles. The experimental result in conjunction with the theoretical calculation reveals that there is strong coupling between the localized electron-hole pair in the SiC QD and the localized surface plasmon in the Ag nanoparticle. It results in resonance energy transfer between them and resultant quenching of the blue surface-defect luminescence of the SiC QDs, leading to uncovering of a hidden near-UV emission band. This study shows that this emission band originates from the interband transition of the 6H-SiC QDs and it exhibits a remarkable quantum confinement effect.

DeepDeath: Learning to predict the underlying cause of death with Big Data.

PubMed

Hassanzadeh, Hamid Reza; Ying Sha; Wang, May D

2017-07-01

Multiple cause-of-death data provides a valuable source of information that can be used to enhance health standards by predicting health related trajectories in societies with large populations. These data are often available in large quantities across U.S. states and require Big Data techniques to uncover complex hidden patterns. We design two different classes of models suitable for large-scale analysis of mortality data, a Hadoop-based ensemble of random forests trained over N-grams, and the DeepDeath, a deep classifier based on the recurrent neural network (RNN). We apply both classes to the mortality data provided by the National Center for Health Statistics and show that while both perform significantly better than the random classifier, the deep model that utilizes long short-term memory networks (LSTMs), surpasses the N-gram based models and is capable of learning the temporal aspect of the data without a need for building ad-hoc, expert-driven features.

A usability study of CPOE's medication administration functions: impact on physician-nurse cooperation.

PubMed

Beuscart-Zéphir, Marie Catherine; Pelayo, Sylvia; Degoulet, Patrice; Anceaux, Françoise; Guerlinger, Sandra; Meaux, Jean-Jacques

2004-01-01

Implementation of CPOE systems in Healthcare Institutions has proven efficient in reducing medication errors but it also induces hidden side-effects on Doctor-Nurse cooperation. We propose a usability engineering approach to this problem. An extensive activity analysis of the medication ordering and administration process was performed in several departments of 3 different hospitals. Two of these hospitals are still using paper-based orders, while the 3rd one is in the roll-out phase of medication functions of its CPOE system. We performed a usability assessment of this CPOE system. The usability assessment uncovered usability problems for the entry of medication administration time scheduling by the physician and revealed that the information can be ambiguous for the nurse. The comparison of cooperation models in both situation shows that users tend to adopt a distributed decision making paradigm in the paper-based situation, while the CPOE system supports a centralized decision making process. This analysis can support recommendation for the re-engineering of the Human-Computer Interface.

Emergent Topological Phenomena in Thin Films of Pyrochlore Iridates

NASA Astrophysics Data System (ADS)

Yang, Bohm-Jung; Nagaosa, Naoto

2014-06-01

Because of the recent development of thin film and artificial superstructure growth techniques, it is possible to control the dimensionality of the system, smoothly between two and three dimensions. In this Letter we unveil the dimensional crossover of emergent topological phenomena in correlated topological materials. In particular, by focusing on the thin film of pyrochlore iridate antiferromagnets grown along the [111] direction, we demonstrate that the thin film can have a giant anomalous Hall conductance, proportional to the thickness of the film, even though there is no Hall effect in 3D bulk material. Moreover, in the case of ultrathin films, a quantized anomalous Hall conductance can be observed, despite the fact that the system is an antiferromagnet. In addition, we uncover the emergence of a new topological phase, the nontrivial topological properties of which are hidden in the bulk insulator and manifest only in thin films. This shows that the thin film of correlated topological materials is a new platform to search for unexplored novel topological phenomena.

Dynamical patterns of cattle trade movements.

PubMed

Bajardi, Paolo; Barrat, Alain; Natale, Fabrizio; Savini, Lara; Colizza, Vittoria

2011-01-01

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions.

Dynamical Patterns of Cattle Trade Movements

PubMed Central

Bajardi, Paolo; Barrat, Alain; Natale, Fabrizio; Savini, Lara; Colizza, Vittoria

2011-01-01

Despite their importance for the spread of zoonotic diseases, our understanding of the dynamical aspects characterizing the movements of farmed animal populations remains limited as these systems are traditionally studied as static objects and through simplified approximations. By leveraging on the network science approach, here we are able for the first time to fully analyze the longitudinal dataset of Italian cattle movements that reports the mobility of individual animals among farms on a daily basis. The complexity and inter-relations between topology, function and dynamical nature of the system are characterized at different spatial and time resolutions, in order to uncover patterns and vulnerabilities fundamental for the definition of targeted prevention and control measures for zoonotic diseases. Results show how the stationarity of statistical distributions coexists with a strong and non-trivial evolutionary dynamics at the node and link levels, on all timescales. Traditional static views of the displacement network hide important patterns of structural changes affecting nodes' centrality and farms' spreading potential, thus limiting the efficiency of interventions based on partial longitudinal information. By fully taking into account the longitudinal dimension, we propose a novel definition of dynamical motifs that is able to uncover the presence of a temporal arrow describing the evolution of the system and the causality patterns of its displacements, shedding light on mechanisms that may play a crucial role in the definition of preventive actions. PMID:21625633

First results from GeMS/GSAOI for project SUNBIRD: Supernovae UNmasked By Infra-Red Detection

NASA Astrophysics Data System (ADS)

Kool, E. C.; Ryder, S.; Kankare, E.; Mattila, S.; Reynolds, T.; McDermid, R. M.; Pérez-Torres, M. A.; Herrero-Illana, R.; Schirmer, M.; Efstathiou, A.; Bauer, F. E.; Kotilainen, J.; Väisänen, P.; Baldwin, C.; Romero-Cañizales, C.; Alberdi, A.

2018-02-01

Core collapse supernova (CCSN) rates suffer from large uncertainties as many CCSNe exploding in regions of bright background emission and significant dust extinction remain unobserved. Such a shortfall is particularly prominent in luminous infrared galaxies (LIRGs), which have high star formation (and thus CCSN) rates and host bright and crowded nuclear regions, where large extinctions and reduced search detection efficiency likely lead to a significant fraction of CCSNe remaining undiscovered. We present the first results of project SUNBIRD (Supernovae UNmasked By Infra-Red Detection), where we aim to uncover CCSNe that otherwise would remain hidden in the complex nuclear regions of LIRGs, and in this way improve the constraints on the fraction that is missed by optical seeing-limited surveys. We observe in the near-infrared 2.15 μm Ks-band, which is less affected by dust extinction compared to the optical, using the multiconjugate adaptive optics imager GeMS/GSAOI on Gemini South, allowing us to achieve a spatial resolution that lets us probe close in to the nuclear regions. During our pilot program and subsequent first full year we have discovered three CCSNe and one candidate with projected nuclear offsets as small as 200 pc. When compared to the total sample of LIRG CCSNe discovered in the near-IR and optical, we show that our method is singularly effective in uncovering CCSNe in nuclear regions and we conclude that the majority of CCSNe exploding in LIRGs are not detected as a result of dust obscuration and poor spatial resolution.

Molecular evidence of cryptic speciation in the "cosmopolitan" excavating sponge Cliona celata (Porifera, Clionaidae).

PubMed

Xavier, J R; Rachello-Dolmen, P G; Parra-Velandia, F; Schönberg, C H L; Breeuwer, J A J; van Soest, R W M

2010-07-01

Over the past several decades molecular tools have shown an enormous potential to aid in the clarification of species boundaries in the marine realm, particularly in morphologically simple groups. In this paper we report a case of cryptic speciation in an allegedly cosmopolitan and ecologically important species-the excavating sponge Cliona celata (Clionaidae, Hadromerida). In the Northeast Atlantic and Mediterranean C. celata displays a discontinuous distribution of its putative growth stages (boring, encrusting, and massive) leading us to investigate its specific status. Phylogenetic reconstructions of mitochondrial (COI, Atp8) and nuclear (28S) gene fragments revealed levels of genetic diversity and divergence compatible with interspecific relationships. We therefore demonstrate C. celata as constituting a species complex comprised of at least four morphologically indistinct species, each showing a far more restricted distribution: two species on the Atlantic European coasts and two on the Mediterranean and adjacent Atlantic coasts (Macaronesian islands). Our results provide further confirmation that the different morphotypes do indeed constitute either growth stages or ecologically adapted phenotypes as boring and massive forms were found in two of the four uncovered species. We additionally provide an overview of the cases of cryptic speciation which have been reported to date within the Porifera, and highlight how taxonomic crypsis may confound scientific interpretation and hamper biotechnological advancement. Our work together with previous studies suggests that overconservative systematic traditions but also morphological stasis have led to genetic complexity going undetected and that a DNA-assisted taxonomy may play a key role in uncovering the hidden diversity in this taxonomic group. Copyright 2010 Elsevier Inc. All rights reserved.

Evolution of bacterial-like phosphoprotein phosphatases in photosynthetic eukaryotes features ancestral mitochondrial or archaeal origin and possible lateral gene transfer.

PubMed

Uhrig, R Glen; Kerk, David; Moorhead, Greg B

2013-12-01

Protein phosphorylation is a reversible regulatory process catalyzed by the opposing reactions of protein kinases and phosphatases, which are central to the proper functioning of the cell. Dysfunction of members in either the protein kinase or phosphatase family can have wide-ranging deleterious effects in both metazoans and plants alike. Previously, three bacterial-like phosphoprotein phosphatase classes were uncovered in eukaryotes and named according to the bacterial sequences with which they have the greatest similarity: Shewanella-like (SLP), Rhizobiales-like (RLPH), and ApaH-like (ALPH) phosphatases. Utilizing the wealth of data resulting from recently sequenced complete eukaryotic genomes, we conducted database searching by hidden Markov models, multiple sequence alignment, and phylogenetic tree inference with Bayesian and maximum likelihood methods to elucidate the pattern of evolution of eukaryotic bacterial-like phosphoprotein phosphatase sequences, which are predominantly distributed in photosynthetic eukaryotes. We uncovered a pattern of ancestral mitochondrial (SLP and RLPH) or archaeal (ALPH) gene entry into eukaryotes, supplemented by possible instances of lateral gene transfer between bacteria and eukaryotes. In addition to the previously known green algal and plant SLP1 and SLP2 protein forms, a more ancestral third form (SLP3) was found in green algae. Data from in silico subcellular localization predictions revealed class-specific differences in plants likely to result in distinct functions, and for SLP sequences, distinctive and possibly functionally significant differences between plants and nonphotosynthetic eukaryotes. Conserved carboxyl-terminal sequence motifs with class-specific patterns of residue substitutions, most prominent in photosynthetic organisms, raise the possibility of complex interactions with regulatory proteins.

A simulation study of gene-by-environment interactions in GWAS implies ample hidden effects

PubMed Central

Marigorta, Urko M.; Gibson, Greg

2014-01-01

The switch to a modern lifestyle in recent decades has coincided with a rapid increase in prevalence of obesity and other diseases. These shifts in prevalence could be explained by the release of genetic susceptibility for disease in the form of gene-by-environment (GxE) interactions. Yet, the detection of interaction effects requires large sample sizes, little replication has been reported, and a few studies have demonstrated environmental effects only after summing the risk of GWAS alleles into genetic risk scores (GRSxE). We performed extensive simulations of a quantitative trait controlled by 2500 causal variants to inspect the feasibility to detect gene-by-environment interactions in the context of GWAS. The simulated individuals were assigned either to an ancestral or a modern setting that alters the phenotype by increasing the effect size by 1.05–2-fold at a varying fraction of perturbed SNPs (from 1 to 20%). We report two main results. First, for a wide range of realistic scenarios, highly significant GRSxE is detected despite the absence of individual genotype GxE evidence at the contributing loci. Second, an increase in phenotypic variance after environmental perturbation reduces the power to discover susceptibility variants by GWAS in mixed cohorts with individuals from both ancestral and modern environments. We conclude that a pervasive presence of gene-by-environment effects can remain hidden even though it contributes to the genetic architecture of complex traits. PMID:25101110

Experimental violation of local causality in a quantum network.

PubMed

Carvacho, Gonzalo; Andreoli, Francesco; Santodonato, Luca; Bentivegna, Marco; Chaves, Rafael; Sciarrino, Fabio

2017-03-16

Bell's theorem plays a crucial role in quantum information processing and thus several experimental investigations of Bell inequalities violations have been carried out over the years. Despite their fundamental relevance, however, previous experiments did not consider an ingredient of relevance for quantum networks: the fact that correlations between distant parties are mediated by several, typically independent sources. Here, using a photonic setup, we investigate a quantum network consisting of three spatially separated nodes whose correlations are mediated by two distinct sources. This scenario allows for the emergence of the so-called non-bilocal correlations, incompatible with any local model involving two independent hidden variables. We experimentally witness the emergence of this kind of quantum correlations by violating a Bell-like inequality under the fair-sampling assumption. Our results provide a proof-of-principle experiment of generalizations of Bell's theorem for networks, which could represent a potential resource for quantum communication protocols.

Experimental violation of local causality in a quantum network

PubMed Central

Carvacho, Gonzalo; Andreoli, Francesco; Santodonato, Luca; Bentivegna, Marco; Chaves, Rafael; Sciarrino, Fabio

2017-01-01

Bell's theorem plays a crucial role in quantum information processing and thus several experimental investigations of Bell inequalities violations have been carried out over the years. Despite their fundamental relevance, however, previous experiments did not consider an ingredient of relevance for quantum networks: the fact that correlations between distant parties are mediated by several, typically independent sources. Here, using a photonic setup, we investigate a quantum network consisting of three spatially separated nodes whose correlations are mediated by two distinct sources. This scenario allows for the emergence of the so-called non-bilocal correlations, incompatible with any local model involving two independent hidden variables. We experimentally witness the emergence of this kind of quantum correlations by violating a Bell-like inequality under the fair-sampling assumption. Our results provide a proof-of-principle experiment of generalizations of Bell's theorem for networks, which could represent a potential resource for quantum communication protocols. PMID:28300068

Experimental violation of local causality in a quantum network

NASA Astrophysics Data System (ADS)

Carvacho, Gonzalo; Andreoli, Francesco; Santodonato, Luca; Bentivegna, Marco; Chaves, Rafael; Sciarrino, Fabio

2017-03-01

Bell's theorem plays a crucial role in quantum information processing and thus several experimental investigations of Bell inequalities violations have been carried out over the years. Despite their fundamental relevance, however, previous experiments did not consider an ingredient of relevance for quantum networks: the fact that correlations between distant parties are mediated by several, typically independent sources. Here, using a photonic setup, we investigate a quantum network consisting of three spatially separated nodes whose correlations are mediated by two distinct sources. This scenario allows for the emergence of the so-called non-bilocal correlations, incompatible with any local model involving two independent hidden variables. We experimentally witness the emergence of this kind of quantum correlations by violating a Bell-like inequality under the fair-sampling assumption. Our results provide a proof-of-principle experiment of generalizations of Bell's theorem for networks, which could represent a potential resource for quantum communication protocols.

Masculinity and undocumented labor migration: injured latino day laborers in San Francisco

PubMed Central

Walter, Nicholas; Bourgois, Philippe; Loinaz, H. Margarita

2009-01-01

Drawing on data collected through clinical practice and ethnographic fieldwork, this study examines the experience of injury, illness and disability among undocumented Latino day laborers in San Francisco. We demonstrate how constructions of masculine identity organize the experience of embodied social suffering among workers who are rendered vulnerable by the structural conditions of undocumented immigrant status. Theoretical concepts from critical medical anthropology and gender studies extend the scholarly analysis of structural violence beyond the primarily economic to uncover how it is embodied at the intimate level as a gendered experience of personal and familial crisis, involving love, respect, betrayal and patriarchal failure. A clinical ethnographic focus on socially structured patriarchal suffering elucidates the causal relationship between macro-forces and individual action with a fuller appreciation of the impact of culture and everyday lived experience. PMID:15210088

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

PubMed Central

2011-01-01

Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. Conclusions A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health. PMID:21529374

Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality.

PubMed

Fenton, Tanis R; Tough, Suzanne C; Lyon, Andrew W; Eliasziw, Misha; Hanley, David A

2011-04-30

Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

A Hidden Active Site in the Potential Drug Target Mycobacterium tuberculosis dUTPase Is Accessible through Small Amplitude Protein Conformational Changes*

PubMed Central

Lopata, Anna; Leveles, Ibolya; Bendes, Ábris Ádám; Viskolcz, Béla; Vértessy, Beáta G.; Jójárt, Balázs; Tóth, Judit

2016-01-01

dUTPases catalyze the hydrolysis of dUTP into dUMP and pyrophosphate to maintain the proper nucleotide pool for DNA metabolism. Recent evidence suggests that dUTPases may also represent a selective drug target in mycobacteria because of the crucial role of these enzymes in maintaining DNA integrity. Nucleotide-hydrolyzing enzymes typically harbor a buried ligand-binding pocket at interdomain or intersubunit clefts, facilitating proper solvent shielding for the catalyzed reaction. The mechanism by which substrate binds this hidden pocket and product is released in dUTPases is unresolved because of conflicting crystallographic and spectroscopic data. We sought to resolve this conflict by using a combination of random acceleration molecular dynamics (RAMD) methodology and structural and biochemical methods to study the dUTPase from Mycobacterium tuberculosis. In particular, the RAMD approach used in this study provided invaluable insights into the nucleotide dissociation process that reconciles all previous experimental observations. Specifically, our data suggest that nucleotide binding takes place as a small stretch of amino acids transiently slides away and partially uncovers the active site. The in silico data further revealed a new dUTPase conformation on the pathway to a relatively open active site. To probe this model, we developed the Trp21 reporter and collected crystallographic, spectroscopic, and kinetic data that confirmed the interaction of Trp21 with the active site shielding C-terminal arm, suggesting that the RAMD method is effective. In summary, our computational simulations and spectroscopic results support the idea that small loop movements in dUTPase allow the shuttlingof the nucleotides between the binding pocket and the solvent. PMID:27815500

A gratuitous β-Lactamase inducer uncovers hidden active site dynamics of the Staphylococcus aureus BlaR1 sensor domain.

PubMed

Frederick, Thomas E; Peng, Jeffrey W

2018-01-01

Increasing evidence shows that active sites of proteins have non-trivial conformational dynamics. These dynamics include active site residues sampling different local conformations that allow for multiple, and possibly novel, inhibitor binding poses. Yet, active site dynamics garner only marginal attention in most inhibitor design efforts and exert little influence on synthesis strategies. This is partly because synthesis requires a level of atomic structural detail that is frequently missing in current characterizations of conformational dynamics. In particular, while the identity of the mobile protein residues may be clear, the specific conformations they sample remain obscure. Here, we show how an appropriate choice of ligand can significantly sharpen our abilities to describe the interconverting binding poses (conformations) of protein active sites. Specifically, we show how 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid (CBAP) exposes otherwise hidden dynamics of a protein active site that binds β-lactam antibiotics. When CBAP acylates (binds) the active site serine of the β-lactam sensor domain of BlaR1 (BlaRS), it shifts the time scale of the active site dynamics to the slow exchange regime. Slow exchange enables direct characterization of inter-converting protein and bound ligand conformations using NMR methods. These methods include chemical shift analysis, 2-d exchange spectroscopy, off-resonance ROESY of the bound ligand, and reduced spectral density mapping. The active site architecture of BlaRS is shared by many β-lactamases of therapeutic interest, suggesting CBAP could expose functional motions in other β-lactam binding proteins. More broadly, CBAP highlights the utility of identifying chemical probes common to structurally homologous proteins to better expose functional motions of active sites.

A window into the future of the Earth, hidden in the jungles of Costa Rica's volcanoes

NASA Astrophysics Data System (ADS)

Fisher, J. B.; Schwandner, F. M.; Asner, G. P.; Schimel, D.; Norby, R. J.; Keller, M.; Pavlick, R.; Braverman, A. J.; Pieri, D. C.; Diaz, J. A.; Gutierrez, M.; Duarte, E. A.; Lewicki, J. L.; Manning, C. E.; Deering, C. D.; Seibt, U.; Miller, G. R.; Drewry, D.; Chambers, J.

2017-12-01

The CO2 fertilization response of the terrestrial biosphere contributes among the largest sensitivities and uncertainties across projections of the Earth's future. The source of that uncertainty can be pinpointed to the largest fluxes in the biosphere: the tropics. Free Air CO2 Enrichment (FACE) experiments have contributed immensely to our understanding of short-term CO2 fertilization, but, outside of a small pilot study in development, have been absent in the tropics. This is largely due to numerous hurdles of not only conducting such experiments in challenging environments, but also due to the need to expand their extent considerably to encompass the enormous diversity of species-level responses, in addition to the need for multi-decadal scale responses. As such, we have remained at a critical impasse in our ability to advance understanding of the response of the tropical biosphere to increasing CO2. Recent discoveries have found a cluster of volcanoes degassing CO2 into tropical ecosystems in Costa Rica at concentrations similar to future Earth atmosphere levels. The degassing has been occurring persistently from 10s to 100s of years over 10s to 100s of square kilometers, at different levels depending on the volcano. Fortuitously, this provides a natural "experiment" across a range of conditions needed to assess a widespread and long-lived tropical ecosystem response to elevated CO2: tree species will have had time to shift in composition, traits, structure, and function. Nonetheless, due both to the challenges with assessing these changes on the ground, and heterogeneity causing problems with coarse-scale satellite remote sensing observations, this "window" into the future of the Earth has remained veiled. Here, we describe an airborne-based plan designed to uncover this gem hidden in the jungles of Costa Rica's volcanoes.

The joy at birth: an interpretive hermeneutic literature review.

PubMed

Crowther, Susan; Smythe, Elizabeth; Spence, Deb

2014-04-01

this literature review examines the experience of joy at birth and what that joy means. The premise is that the whole of the birthing experience has not been fully explicated in the literature and that something of significance remains unexplored and unspoken. It is argued that a hermeneutic phenomenological approach to reviewing literature provides unique insights and leads to deeper understandings about birth and the experience of joy that attunes at that moment. the philosophical underpinnings informed by Heidegger and Gadamer are central to this review and therefore the process of reviewing literature hermeneutically is described. Heideggerian phenomenology is used as the method to ask the questions of the literature in order that concealed and hidden experiences of joy at birth are made visible where they are gleaned from the literature. A hermeneutic lens is used to uncover relationships within the phenomenon of joy at birth and meaning. although a vast birth literature was reviewed joy at birth was often ignored, hidden or covered over. Reviewing the literature on relationships, professional presence, place of birth, birth satisfaction studies and birth as peak and spiritual experience provides glimpses of the phenomenon 'joy at birth'. it is argued that joy at birth remains largely neglected as a phenomenon worthy of consideration. Plausible interpretations are presented that suggest that joy at birth points to something significant and meaningful. Spiritual and sacred meaning is alluded to in the papers reviewed yet the majority of papers that investigate birth leave this meaning unspoken. The review highlights a need for further thinking and questioning about birth that would direct on-going investigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using chemical organization theory for model checking

PubMed Central

Kaleta, Christoph; Richter, Stephan; Dittrich, Peter

2009-01-01

Motivation: The increasing number and complexity of biomodels makes automatic procedures for checking the models' properties and quality necessary. Approaches like elementary mode analysis, flux balance analysis, deficiency analysis and chemical organization theory (OT) require only the stoichiometric structure of the reaction network for derivation of valuable information. In formalisms like Systems Biology Markup Language (SBML), however, information about the stoichiometric coefficients required for an analysis of chemical organizations can be hidden in kinetic laws. Results: First, we introduce an algorithm that uncovers stoichiometric information that might be hidden in the kinetic laws of a reaction network. This allows us to apply OT to SBML models using modifiers. Second, using the new algorithm, we performed a large-scale analysis of the 185 models contained in the manually curated BioModels Database. We found that for 41 models (22%) the set of organizations changes when modifiers are considered correctly. We discuss one of these models in detail (BIOMD149, a combined model of the ERK- and Wnt-signaling pathways), whose set of organizations drastically changes when modifiers are considered. Third, we found inconsistencies in 5 models (3%) and identified their characteristics. Compared with flux-based methods, OT is able to identify those species and reactions more accurately [in 26 cases (14%)] that can be present in a long-term simulation of the model. We conclude that our approach is a valuable tool that helps to improve the consistency of biomodels and their repositories. Availability: All data and a JAVA applet to check SBML-models is available from http://www.minet.uni-jena.de/csb/prj/ot/tools Contact: dittrich@minet.uni-jena.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19468053

The causal attributions of nursing students toward adolescent survivors of brain injury.

PubMed

Linden, Mark A; McClure, John

2012-01-01

The hidden nature of brain injury means that it is often difficult for people to understand the sometimes challenging behaviors that individuals exhibit. The misattribution of these behaviors may lead to a lack of consideration and public censure if the individual is seen as simply misbehaving. The aim of this study was to explore the impact of visual cues indicating the presence or absence of brain injury on prejudice, desire for social interaction, and causal attributions of nursing and computing science students. An independent-groups design was employed in this research, which recruited 190 first-year nursing students and 194 first-year computing science students from a major university in Belfast, UK. A short passage describing an adolescent's behavior after a brain injury, together with one of three images portraying a young adolescent with a scar, a head dressing, or neither of these, was given to participants. They were then asked to answer questions relating to prejudice, social interaction, locus of control, and causal attributions. The attributional statements suggested that the character's behavior could be the result of brain injury or adolescence. Analysis of variance demonstrated a statistically significant difference between the student groups, where nursing students (M = 45.17, SD = 4.69) desired more social interaction with the fictional adolescent than their computer science peers (M = 38.64, SD = 7.69). Further, analysis of variance showed a main effect of image on the attributional statement that described adolescence as a suitable explanation for the character's lack of self-confidence. Attributions of brain injury were influenced by the presence of a visible but potentially specious indicator of injury. This suggests that survivors of brain injury who do not display any outward indicator may receive less care and face expectations to behave in a manner consistent with the norms of society. If their injury does not allow them to meet with these expectations, they may face public censure and discrimination.

Clinical analysis of genome next-generation sequencing data using the Omicia platform

PubMed Central

Coonrod, Emily M; Margraf, Rebecca L; Russell, Archie; Voelkerding, Karl V; Reese, Martin G

2013-01-01

Aims Next-generation sequencing is being implemented in the clinical laboratory environment for the purposes of candidate causal variant discovery in patients affected with a variety of genetic disorders. The successful implementation of this technology for diagnosing genetic disorders requires a rapid, user-friendly method to annotate variants and generate short lists of clinically relevant variants of interest. This report describes Omicia’s Opal platform, a new software tool designed for variant discovery and interpretation in a clinical laboratory environment. The software allows clinical scientists to process, analyze, interpret and report on personal genome files. Materials & Methods To demonstrate the software, the authors describe the interactive use of the system for the rapid discovery of disease-causing variants using three cases. Results & Conclusion Here, the authors show the features of the Opal system and their use in uncovering variants of clinical significance. PMID:23895124

Stigma as ego depletion: how being the target of prejudice affects self-control.

PubMed

Inzlicht, Michael; McKay, Linda; Aronson, Joshua

2006-03-01

This research examined whether stigma diminishes people's ability to control their behaviors. Because coping with stigma requires self-regulation, and self-regulation is a limited-capacity resource, we predicted that individuals belonging to stigmatized groups are less able to regulate their own behavior when they become conscious of their stigmatizing status or enter threatening environments. Study 1 uncovered a correlation between stigma sensitivity and self-regulation; the more Black college students were sensitive to prejudice, the less self-control they reported having. By experimentally activating stigma, Studies 2 and 3 provided causal evidence for stigma's ego-depleting qualities: When their stigma was activated, stigmatized participants (Black students and females) showed impaired self-control in two very different domains (attentional and physical self-regulation). These results suggest that (a) stigma is ego depleting and (b) coping with it can weaken the ability to control and regulate one's behaviors in domains unrelated to the stigma.

GCR Modulation by Small-Scale Features in the Interplanetary Medium

NASA Astrophysics Data System (ADS)

Jordan, A. P.; Spence, H. E.; Blake, J. B.; Mulligan, T. L.; Shaul, D. N.; Galametz, M.

2007-12-01

In an effort to uncover the properties of structures in the interplanetary medium (IPM) that modulate galactic cosmic rays (GCR) on short time-scales (from hours to days), we study periods of differing conditions in the IPM. We analyze GCR variations from spacecraft both inside and outside the magnetosphere, using the High Sensitivity Telescope (HIST) on Polar and the Spectrometer for INTEGRAL (SPI). We seek causal correlations between the observed GCR modulations and structures in the solar wind plasma and interplanetary magnetic field, as measured concurrently with ACE and/or Wind. Our analysis spans time-/size-scale variations ranging from classic Forbush decreases (Fds), to substructure embedded within Fds, to much smaller amplitude and shorter duration variations observed during comparatively benign interplanetary conditions. We compare and contrast the conditions leading to the range of different GCR responses to modulating structures in the IPM.

Investigation of a “Sharps” Incident

DOE PAGES

Cournoyer, Michael Edward; Trujillo, Stanley; Schreiber, Stephen Bruce

2016-08-03

Special nuclear material research, process development, technology demonstration, and manufacturing capabilities are provided at the Los Alamos National Laboratory Plutonium Facility. Engineered barriers provide the most effective protection from radioactive and hazardous materials. The Worker Safety Security Team augments these passive safety feature by investigating incidents to identify appropriate prevention and mitigation measures. “Learning Teams” facilitate employee feedback loop and integration toward process improvement. Here, this article reports an investigation of a “Sharps” incident and reviews a case study of a technician that cuts his left thumb while making a gasket. Causal analysis of the sharps incident uncovered contributing factorsmore » that created the environment in which the incident occurred. Finally, latent organizational conditions that created error-likely situations or weakened defenses were identified and controlled. Effective improvements that reduce the probability or consequence of similar sharps incidents were implemented.« less

Mediation and moderation of treatment effects in randomised controlled trials of complex interventions.

PubMed

Emsley, Richard; Dunn, Graham; White, Ian R

2010-06-01

Complex intervention trials should be able to answer both pragmatic and explanatory questions in order to test the theories motivating the intervention and help understand the underlying nature of the clinical problem being tested. Key to this is the estimation of direct effects of treatment and indirect effects acting through intermediate variables which are measured post-randomisation. Using psychological treatment trials as an example of complex interventions, we review statistical methods which crucially evaluate both direct and indirect effects in the presence of hidden confounding between mediator and outcome. We review the historical literature on mediation and moderation of treatment effects. We introduce two methods from within the existing causal inference literature, principal stratification and structural mean models, and demonstrate how these can be applied in a mediation context before discussing approaches and assumptions necessary for attaining identifiability of key parameters of the basic causal model. Assuming that there is modification by baseline covariates of the effect of treatment (i.e. randomisation) on the mediator (i.e. covariate by treatment interactions), but no direct effect on the outcome of these treatment by covariate interactions leads to the use of instrumental variable methods. We describe how moderation can occur through post-randomisation variables, and extend the principal stratification approach to multiple group methods with explanatory models nested within the principal strata. We illustrate the new methodology with motivating examples of randomised trials from the mental health literature.

Complexity in pH-Dependent Ribozyme Kinetics: Dark pKa Shifts and Wavy Rate-pH Profiles.

PubMed

Frankel, Erica A; Bevilacqua, Philip C

2018-02-06

Charged bases occur in RNA enzymes, or ribozymes, where they play key roles in catalysis. Cationic bases donate protons and perform electrostatic catalysis, while anionic bases accept protons. We previously published simulations of rate-pH profiles for ribozymes in terms of species plots for the general acid and general base that have been useful for understanding how ribozymes respond to pH. In that study, we did not consider interaction between the general acid and general base or interaction with other species on the RNA. Since that report, diverse small ribozyme classes have been discovered, many of which have charged nucleobases or metal ions in the active site that can either directly interact and participate in catalysis or indirectly interact as "influencers". Herein, we simulate experimental rate-pH profiles in terms of species plots in which reverse protonated charged nucleobases interact. These analyses uncover two surprising features of pH-dependent enzyme kinetics. (1) Cooperativity between the general acid and general base enhances population of the functional forms of a ribozyme and manifests itself as hidden or "dark" pK a shifts, real pK a shifts that accelerate the reaction but are not readily observed by standard experimental approaches, and (2) influencers favorably shift the pK a s of proton-transferring nucleobases and manifest themselves as "wavy" rate-pH profiles. We identify parallels with the protein enzyme literature, including reverse protonation and wavelike behavior, while pointing out that RNA is more prone to reverse protonation. The complexities uncovered, which arise from simple pairwise interactions, should aid deconvolution of complex rate-pH profiles for RNA and protein enzymes and suggest veiled catalytic devices for promoting catalysis that can be tested by experiment and calculation.

Accurate detection of hierarchical communities in complex networks based on nonlinear dynamical evolution

NASA Astrophysics Data System (ADS)

Zhuo, Zhao; Cai, Shi-Min; Tang, Ming; Lai, Ying-Cheng

2018-04-01

One of the most challenging problems in network science is to accurately detect communities at distinct hierarchical scales. Most existing methods are based on structural analysis and manipulation, which are NP-hard. We articulate an alternative, dynamical evolution-based approach to the problem. The basic principle is to computationally implement a nonlinear dynamical process on all nodes in the network with a general coupling scheme, creating a networked dynamical system. Under a proper system setting and with an adjustable control parameter, the community structure of the network would "come out" or emerge naturally from the dynamical evolution of the system. As the control parameter is systematically varied, the community hierarchies at different scales can be revealed. As a concrete example of this general principle, we exploit clustered synchronization as a dynamical mechanism through which the hierarchical community structure can be uncovered. In particular, for quite arbitrary choices of the nonlinear nodal dynamics and coupling scheme, decreasing the coupling parameter from the global synchronization regime, in which the dynamical states of all nodes are perfectly synchronized, can lead to a weaker type of synchronization organized as clusters. We demonstrate the existence of optimal choices of the coupling parameter for which the synchronization clusters encode accurate information about the hierarchical community structure of the network. We test and validate our method using a standard class of benchmark modular networks with two distinct hierarchies of communities and a number of empirical networks arising from the real world. Our method is computationally extremely efficient, eliminating completely the NP-hard difficulty associated with previous methods. The basic principle of exploiting dynamical evolution to uncover hidden community organizations at different scales represents a "game-change" type of approach to addressing the problem of community detection in complex networks.

Observational Signatures Of Agn Feedback Across Cosmic Time

NASA Astrophysics Data System (ADS)

Wylezalek, Dominika

2017-06-01

While many compelling models of AGN feedback exist, there is no clear data-driven picture of how winds are launched, how they propagate through the galaxy and what impact they have on the galactic gas. Recent work suggests that AGN luminosity plays an important role. The following described projects focus on understanding the power, reach and impact of feedback processes exerted by AGN of different power. I first describe recent efforts in our group of relating feedback signatures in powerful quasars to the specific star formation rate in their host galaxies, where our results are consistent with the AGN having a `negative' impact through feedback on the galaxies' star formation history. Feedback signatures seem to be best observable in gas-rich galaxies where the coupling of the AGN-driven wind to the gas is strongest, in agreement with recent simulations. But how and where does this quenching happen? Is it accomplished through the mechanical action of jets or through nuclear winds driven by radiation pressure? Finally, I show that AGN signatures and AGN-driven winds can be easily hidden and not be apparent in the integrated spectrum of a galaxy hosting a low/intermediate-luminosity AGN. Using data from the new SDSS-IV MaNGA survey, we have developed a new AGN selection algorithm tailored to IFU data and we are uncovering a much more nuanced picture of AGN activity allowing us to discover AGN signatures at large distances from the galaxy center. This implies that large IFU surveys, such as the SDSS-IV MaNGA survey, might uncover many previously unknown AGN and feedback signatures related to them. Outflows and feedback from low- and intermediate-luminosity AGN might have been underestimated in the past but can potentially significantly contribute to the AGN/host-galaxy self-regulation.

Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain

PubMed Central

Pilaz, Louis-Jan; Silver, Debra L.

2015-01-01

The cerebral cortex, the brain structure responsible for our higher cognitive functions, is built during embryonic development in a process called corticogenesis. During corticogenesis, neural stem cells generate distinct populations of progenitors and excitatory neurons. These new neurons migrate radially in the cortex, eventually forming neuronal layers and establishing synaptic connections with other neurons both within and outside the cortex. Perturbations to corticogenesis can result in severe neurodevelopmental disorders, thus emphasizing the need to better understand molecular regulation of brain development. Recent studies in both model organisms and humans have collectively highlighted roles for post-transcriptional regulation in virtually all steps of corticogenesis. Genomic approaches have revealed global RNA changes associated with spatial and temporal regulation of cortical development. Additionally, genetic studies have uncovered RNA-binding proteins (RBPs) critical for cell proliferation, differentiation, and migration within the developing neocortex. Many of these same RBPs play causal roles in neurodevelopmental pathologies. In the developing neocortex, RBPs influence diverse steps of mRNA metabolism, including splicing, stability, translation, and localization. With the advent of new technologies, researchers have begun to uncover key transcripts regulated by these RBPs. Given the complexity of the developing mammalian cortex, a major challenge for the future will be to understand how dynamic RNA regulation occurs within heterogeneous cell populations, across space and time. In sum, post-transcriptional regulation has emerged as a critical mechanism for driving corticogenesis and exciting direction of future research. PMID:26088328

Monsters and babies from the first/IRAS survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Bruegel, W J M

Radio continuum emission at cm wavelengths is relatively little affected by extinction. When combined with far-infrared (FIR) surveys this provides for a convenient and unbiased method to select (radio-loud) AGN and starbursts deeply embedded in gas and dust-rich galaxies. Such radio-selected FIR samples are useful for detailed investigations of the complex relationships between (radio) galaxy and starburst activity, and to determine whether ULIRGs are powered by hidden quasars (monsters) or young stars (babies). We present the results of a large program to obtain identifications and spectra of radio-sleected, optically faint IRAS/FSC objects using the FIRST/VLA 20 cm survey (Becker, Whitemore » and Helfand 1995). These objects are all radio-'quiet' in the sense that their radio power/FIR luminosities follow the well-known radio/FIR relationship for star forming galaxies. We compare these results to a previous study by our group of a sample of radio-'loud' IRAS/FSC ULIRGs selected from the Texas 365 MHz survey (Douglas et al. 1996). Many of these objects also show evidence for dominant, A-type stellar populations, as well as high ionization lines usually associated with AGN. These radio-loud ULIRGs have properties intermediate between those of starbursts and quasars, suggesting a possibile evolutionary connection. Deep Keck spectroscopic observations of three ULIRGs from these samples are presented, including high signal-to-noise spectropolarimetry. The polarimetry observations failed to show evidence of a hidden quasar in polarized (scattered) light in the two systems in which the stellar light was dominated by A-type stars. Although observations of a larger sample would be needed to allow a general conclusion, our current data suggest that a large fraction of ULIRGs may be powered by luminous starbursts, not by hidden, luminous AGN (quasars). While we used radio-selected FIR sources to search for evidence of a causal AGN/starburst connection, we conclude our presentation with a dramatic example of an AGN/starburst object from an entirely unrelated quasar survey selected at the opposite, blue end of the spectrum.« less

Understanding women's sleep management: beyond medicalization-healthicization?

PubMed

Hislop, Jenny; Arber, Sara

2003-11-01

This paper addresses sleep, which to date has been a neglected area within the sociology of health and illness. We explore the extent to which the concepts of medicalization and healthicization provide appropriate models for understanding the management of women's sleep disruption. The prescription of sleeping pills remains as an indicator of the medicalization of sleep, while the trend towards the healthicization of sleep as part of healthy lifestyle practice is reflected in the increased focus of the media, pharmaceutical and complementary health care industries on sleep. The paper analyses qualitative data on women aged 40 and over to argue that the medicalization-healthicization framework fails to encapsulate a complete understanding of how women manage sleep disruption within the social context of their lives. It suggests that by looking inside the world of women's sleep we uncover a hidden dimension of self-directed personalized activity which plays a key role in women's response to sleep disruption. We propose an alternative model for the management of women's sleep which incorporates a core of personalised activity, linked to strategies associated with healthicization and medicalization.

A New Look at the Eclipse Timing Variation Diagram Analysis of Selected 3-body W UMa Systems

NASA Astrophysics Data System (ADS)

Christopoulou, P.-E.; Papageorgiou, A.

2015-07-01

The light travel effect produced by the presence of tertiary components can reveal much about the origin and evolution of over-contact binaries. Monitoring of W UMa systems over the last decade and/or the use of publicly available photometric surveys (NSVS, ASAS, etc.) has uncovered or suggested the presence of many unseen companions, which calls for an in-depth investigation of the parameters derived from cyclic period variations in order to confirm or reject the assumption of hidden companion(s). Progress in the analysis of eclipse timing variations is summarized here both from the empirical and the theoretical points of view, and a more extensive investigation of the proposed orbital parameters of third bodies is proposed. The code we have developed for this, implemented in Python, is set up to handle heuristic scanning with parameter perturbation in parameter space, and to establish realistic uncertainties from the least squares fitting. A computational example is given for TZ Boo, a W UMa system with a spectroscopically detected third component. Future options to be implemented include MCMC and bootstrapping.

Accessing protein conformational ensembles using room-temperature X-ray crystallography

PubMed Central

Fraser, James S.; van den Bedem, Henry; Samelson, Avi J.; Lang, P. Therese; Holton, James M.; Echols, Nathaniel; Alber, Tom

2011-01-01

Modern protein crystal structures are based nearly exclusively on X-ray data collected at cryogenic temperatures (generally 100 K). The cooling process is thought to introduce little bias in the functional interpretation of structural results, because cryogenic temperatures minimally perturb the overall protein backbone fold. In contrast, here we show that flash cooling biases previously hidden structural ensembles in protein crystals. By analyzing available data for 30 different proteins using new computational tools for electron-density sampling, model refinement, and molecular packing analysis, we found that crystal cryocooling remodels the conformational distributions of more than 35% of side chains and eliminates packing defects necessary for functional motions. In the signaling switch protein, H-Ras, an allosteric network consistent with fluctuations detected in solution by NMR was uncovered in the room-temperature, but not the cryogenic, electron-density maps. These results expose a bias in structural databases toward smaller, overpacked, and unrealistically unique models. Monitoring room-temperature conformational ensembles by X-ray crystallography can reveal motions crucial for catalysis, ligand binding, and allosteric regulation. PMID:21918110

Dark Energy and Dark Matter Hidden in the Geometry of Space?

NASA Astrophysics Data System (ADS)

Buchert, Thomas

A spatially flat and infinite Universe in the form of a "concordant" standard model of cosmology rules present-day thinking of cosmologists. The price to pay is an unknown physical origin of Dark Energy and Dark Matter that are supposed to exist and even appear to rule the dynamics of our Universe. A growing number of cosmologists question the existence of dark constituents: the standard model of cosmology may be just too simple, since it neglects the influence of structure in the Universe on its global expansion history. The key-issue appears to be the curvature of space: the formation of structure interacts with the geometry of space, changing our global picture of the Universe. This chapter explains the underlying mechanism that works in the right direction to uncover the dark faces of the standard model of cosmology. If successful, this novel approach furnishes a new paradigm of modern cosmology. Hundreds of researchers have recently embarked into studies of this new subject. We understand much at present, but there are many open questions.

Yearning, learning, and conceding: reasons men and women change their childbearing intentions.

PubMed

Iacovou, Maria; Tavares, Lara Patrício

2011-01-01

People's childbearing intentions change over the course of their reproductive lives. These changes have been conceptualized as occurring in response to the realization that an individual is unlikely to achieve his or her intended fertility, because of constraints such as the "biological clock" or lack of a partner. In this article, we find that changes to child-bearing plans are influenced by a much wider range of factors than this. People change their plans in response to the wishes of their partners, in response to social norms, as the result of repartnering, and as the result of learning about the costs and benefits of parenthood; there are also differences between the factors that influence men's and women's decision-making. In a departure from existing studies in this area, we use a flexible analytical framework that enables us to analyze increases in planned fertility separately from decreases. This allows us to uncover several complexities of the decision-making process that would otherwise be hidden, and leads us to conclude that the determinants of increases in planned fertility are not simply equal and opposite to the determinants of decreases.

Uncovering the hidden impacts of inequality on mental health: a global study.

PubMed

Yu, Shoukai

2018-05-18

Women are nearly twice as likely as men to suffer from mental illness. This gender disparity in depressive disorders may relate to social inequalities and living standards across nations. Currently, these disparities were not reflected at the level of health policies. This study utilized global data for depressive disorders and socioeconomic data from the United Nations' World Bank databases and Global Burden of Disease database to demonstrate the correlation between social inequality and gender disparities in mental health. This study investigated the association among the ratio of female to male depressive disorder rates, gross domestic product, the GINI Index, and the gender inequality index for 122 countries. The research yielded some major findings. First, there exists a significant correlation between gender inequality and gender disparities in mental health. Second, the GINI index is significantly associated with male-but not female-depressive disorder rates. Third, gender disparities in depressive disorders are associated with a country's wealth. These findings can help to inform society, policy-makers, and clinicians to improve the overall health level globally.

Bioinformatic perspectives on NRPS/PKS megasynthases: advances and challenges.

PubMed

Jenke-Kodama, Holger; Dittmann, Elke

2009-07-01

The increased understanding of both fundamental principles and mechanistic variations of NRPS/PKS megasynthases along with the unprecedented availability of microbial sequences has inspired a number of in silico studies of both enzyme families. The insights that can be extracted from these analyses go far beyond a rough classification of data and have turned bioinformatics into a frontier field of natural products research. As databases are flooded with NRPS/PKS gene sequence of microbial genomes and metagenomes, increasingly reliable structural prediction methods can help to uncover hidden treasures. Already, phylogenetic analyses have revealed that NRPS/PKS pathways should not simply be regarded as enzyme complexes, specifically evolved to product a selected natural product. Rather, they represent a collection of genetic opinions, allowing biosynthetic pathways to be shuffled in a process of perpetual chemical innovations and pathways diversification in nature can give impulses for specificities, protein interactions and genetic engineering of libraries of novel peptides and polyketides. The successful translation of the knowledge obtained from bioinformatic dissection of NRPS/PKS megasynthases into new techniques for drug discovery and design remain challenges for the future.

Genetic characterization and disease mechanism of retinitis pigmentosa; current scenario.

PubMed

Ali, Muhammad Umar; Rahman, Muhammad Saif Ur; Cao, Jiang; Yuan, Ping Xi

2017-08-01

Retinitis pigmentosa is a group of genetically transmitted disorders affecting 1 in 3000-8000 individual people worldwide ultimately affecting the quality of life. Retinitis pigmentosa is characterized as a heterogeneous genetic disorder which leads by progressive devolution of the retina leading to a progressive visual loss. It can occur in syndromic (with Usher syndrome and Bardet-Biedl syndrome) as well as non-syndromic nature. The mode of inheritance can be X-linked, autosomal dominant or autosomal recessive manner. To date 58 genes have been reported to associate with retinitis pigmentosa most of them are either expressed in photoreceptors or the retinal pigment epithelium. This review focuses on the disease mechanisms and genetics of retinitis pigmentosa. As retinitis pigmentosa is tremendously heterogeneous disorder expressing a multiplicity of mutations; different variations in the same gene might induce different disorders. In recent years, latest technologies including whole-exome sequencing contributing effectively to uncover the hidden genesis of retinitis pigmentosa by reporting new genetic mutations. In future, these advancements will help in better understanding the genotype-phenotype correlations of disease and likely to develop new therapies.

Delta II - SIRTF

NASA Image and Video Library

2003-03-06

The Space Infrared Telescope Facility (SIRTF) is uncovered in the clean room of Building AE to permit workers access to the spacecraft to begin final preparations for its launch aboard a Delta II rocket. The observatory was shipped to Florida from the Lockheed Martin plant in Sunnyvale, Calif. SIRTF will obtain images and spectra by detecting the infrared energy, or heat, radiated by objects in space between wavelengths of 3 and 180 microns (1 micron is one-millionth of a meter). Most of this infrared radiation is blocked by the Earth's atmosphere and cannot be observed from the ground. Consisting of an 0.85-meter telescope and three cryogenically cooled science instruments, SIRTF is one of NASA's largest infrared telescopes to be launched. Its highly sensitive instruments will give a unique view of the Universe and peer into regions of space that are hidden from optical telescopes on the ground or orbiting telescopes such as the Hubble Space Telescope. SIRTF is scheduled for launch April 15 at 4:34:07 a.m. EDT from Launch Complex 17-B, Cape Canaveral Air Force Station.

IDEAL: Images Across Domains, Experiments, Algorithms and Learning

NASA Astrophysics Data System (ADS)

Ushizima, Daniela M.; Bale, Hrishikesh A.; Bethel, E. Wes; Ercius, Peter; Helms, Brett A.; Krishnan, Harinarayan; Grinberg, Lea T.; Haranczyk, Maciej; Macdowell, Alastair A.; Odziomek, Katarzyna; Parkinson, Dilworth Y.; Perciano, Talita; Ritchie, Robert O.; Yang, Chao

2016-11-01

Research across science domains is increasingly reliant on image-centric data. Software tools are in high demand to uncover relevant, but hidden, information in digital images, such as those coming from faster next generation high-throughput imaging platforms. The challenge is to analyze the data torrent generated by the advanced instruments efficiently, and provide insights such as measurements for decision-making. In this paper, we overview work performed by an interdisciplinary team of computational and materials scientists, aimed at designing software applications and coordinating research efforts connecting (1) emerging algorithms for dealing with large and complex datasets; (2) data analysis methods with emphasis in pattern recognition and machine learning; and (3) advances in evolving computer architectures. Engineering tools around these efforts accelerate the analyses of image-based recordings, improve reusability and reproducibility, scale scientific procedures by reducing time between experiments, increase efficiency, and open opportunities for more users of the imaging facilities. This paper describes our algorithms and software tools, showing results across image scales, demonstrating how our framework plays a role in improving image understanding for quality control of existent materials and discovery of new compounds.

Smart Health - Potential and Pathways: A Survey

NASA Astrophysics Data System (ADS)

Arulananthan, C.; Hanifa, Sabibullah Mohamed

2017-08-01

Healthcare is an imperative key field of research, where individuals or groups can be engaged in the self-tracking of any kind of biological, physical, behavioral, or environmental information. In a massive health care data, the valuable information is hidden. The quantity of the available unstructured data has been expanding on an exponential scale. The newly developing Disruptive Technologies can handle many challenges that face data analysis and ability to extract valuable information via data analytics. Connected Wellness in Healthcare would retrieve patient’s physiological, pathological and behavioral parameters through sensors to perform inner workings of human body analysis. Disruptive technologies can take us from a reactive illness-driven to a proactive wellness-driven system in health care. It is need to be strive and create a smart health system towards wellness-driven instead of being illness-driven, today’s biggest problem in health care. Wellness-driven-analytics application help to promote healthiest living environment called “Smart Health”, deliver empower based quality of living. The contributions of this survey reveals and opens (touches uncovered areas) the possible doors in the line of research on smart health and its computing technologies.

CollaborationViz: Interactive Visual Exploration of Biomedical Research Collaboration Networks

PubMed Central

Bian, Jiang; Xie, Mengjun; Hudson, Teresa J.; Eswaran, Hari; Brochhausen, Mathias; Hanna, Josh; Hogan, William R.

2014-01-01

Social network analysis (SNA) helps us understand patterns of interaction between social entities. A number of SNA studies have shed light on the characteristics of research collaboration networks (RCNs). Especially, in the Clinical Translational Science Award (CTSA) community, SNA provides us a set of effective tools to quantitatively assess research collaborations and the impact of CTSA. However, descriptive network statistics are difficult for non-experts to understand. In this article, we present our experiences of building meaningful network visualizations to facilitate a series of visual analysis tasks. The basis of our design is multidimensional, visual aggregation of network dynamics. The resulting visualizations can help uncover hidden structures in the networks, elicit new observations of the network dynamics, compare different investigators and investigator groups, determine critical factors to the network evolution, and help direct further analyses. We applied our visualization techniques to explore the biomedical RCNs at the University of Arkansas for Medical Sciences – a CTSA institution. And, we created CollaborationViz, an open-source visual analytical tool to help network researchers and administration apprehend the network dynamics of research collaborations through interactive visualization. PMID:25405477

Multilayer Brain Networks

NASA Astrophysics Data System (ADS)

Vaiana, Michael; Muldoon, Sarah Feldt

2018-01-01

The field of neuroscience is facing an unprecedented expanse in the volume and diversity of available data. Traditionally, network models have provided key insights into the structure and function of the brain. With the advent of big data in neuroscience, both more sophisticated models capable of characterizing the increasing complexity of the data and novel methods of quantitative analysis are needed. Recently, multilayer networks, a mathematical extension of traditional networks, have gained increasing popularity in neuroscience due to their ability to capture the full information of multi-model, multi-scale, spatiotemporal data sets. Here, we review multilayer networks and their applications in neuroscience, showing how incorporating the multilayer framework into network neuroscience analysis has uncovered previously hidden features of brain networks. We specifically highlight the use of multilayer networks to model disease, structure-function relationships, network evolution, and link multi-scale data. Finally, we close with a discussion of promising new directions of multilayer network neuroscience research and propose a modified definition of multilayer networks designed to unite and clarify the use of the multilayer formalism in describing real-world systems.

A survey of context recognition in surgery.

PubMed

Pernek, Igor; Ferscha, Alois

2017-10-01

With the introduction of operating rooms of the future context awareness has gained importance in the surgical environment. This paper organizes and reviews different approaches for recognition of context in surgery. Major electronic research databases were queried to obtain relevant publications submitted between the years 2010 and 2015. Three different types of context were identified: (i) the surgical workflow context, (ii) surgeon's cognitive and (iii) technical state context. A total of 52 relevant studies were identified and grouped based on the type of context detected and sensors used. Different approaches were summarized to provide recommendations for future research. There is still room for improvement in terms of methods used and evaluations performed. Machine learning should be used more extensively to uncover hidden relationships between different properties of the surgeon's state, particularly when performing cognitive context recognition. Furthermore, validation protocols should be improved by performing more evaluations in situ and with a higher number of unique participants. The paper also provides a structured outline of recent context recognition methods to facilitate development of new generation context-aware surgical support systems.

Three-dimensional reconstruction of highly complex microscopic samples using scanning electron microscopy and optical flow estimation.

PubMed

Baghaie, Ahmadreza; Pahlavan Tafti, Ahmad; Owen, Heather A; D'Souza, Roshan M; Yu, Zeyun

2017-01-01

Scanning Electron Microscope (SEM) as one of the major research and industrial equipment for imaging of micro-scale samples and surfaces has gained extensive attention from its emerge. However, the acquired micrographs still remain two-dimensional (2D). In the current work a novel and highly accurate approach is proposed to recover the hidden third-dimension by use of multi-view image acquisition of the microscopic samples combined with pre/post-processing steps including sparse feature-based stereo rectification, nonlocal-based optical flow estimation for dense matching and finally depth estimation. Employing the proposed approach, three-dimensional (3D) reconstructions of highly complex microscopic samples were achieved to facilitate the interpretation of topology and geometry of surface/shape attributes of the samples. As a byproduct of the proposed approach, high-definition 3D printed models of the samples can be generated as a tangible means of physical understanding. Extensive comparisons with the state-of-the-art reveal the strength and superiority of the proposed method in uncovering the details of the highly complex microscopic samples.

Minimum of the order parameter fluctuations of seismicity before major earthquakes in Japan.

PubMed

Sarlis, Nicholas V; Skordas, Efthimios S; Varotsos, Panayiotis A; Nagao, Toshiyasu; Kamogawa, Masashi; Tanaka, Haruo; Uyeda, Seiya

2013-08-20

It has been shown that some dynamic features hidden in the time series of complex systems can be uncovered if we analyze them in a time domain called natural time χ. The order parameter of seismicity introduced in this time domain is the variance of χ weighted for normalized energy of each earthquake. Here, we analyze the Japan seismic catalog in natural time from January 1, 1984 to March 11, 2011, the day of the M9 Tohoku earthquake, by considering a sliding natural time window of fixed length comprised of the number of events that would occur in a few months. We find that the fluctuations of the order parameter of seismicity exhibit distinct minima a few months before all of the shallow earthquakes of magnitude 7.6 or larger that occurred during this 27-y period in the Japanese area. Among the minima, the minimum before the M9 Tohoku earthquake was the deepest. It appears that there are two kinds of minima, namely precursory and nonprecursory, to large earthquakes.

Self-organization in irregular landscapes: Detecting autogenic interactions from field data using descriptive statistics and dynamical systems theory

NASA Astrophysics Data System (ADS)

Larsen, L.; Watts, D.; Khurana, A.; Anderson, J. L.; Xu, C.; Merritts, D. J.

2015-12-01

The classic signal of self-organization in nature is pattern formation. However, the interactions and feedbacks that organize depositional landscapes do not always result in regular or fractal patterns. How might we detect their existence and effects in these "irregular" landscapes? Emergent landscapes such as newly forming deltaic marshes or some restoration sites provide opportunities to study the autogenic processes that organize landscapes and their physical signatures. Here we describe a quest to understand autogenic vs. allogenic controls on landscape evolution in Big Spring Run, PA, a landscape undergoing restoration from bare-soil conditions to a target wet meadow landscape. The contemporary motivation for asking questions about autogenic vs. allogenic controls is to evaluate how important initial conditions or environmental controls may be for the attainment of management objectives. However, these questions can also inform interpretation of the sedimentary record by enabling researchers to separate signals that may have arisen through self-organization processes from those resulting from environmental perturbations. Over three years at Big Spring Run, we mapped the dynamic evolution of floodplain vegetation communities and distributions of abiotic variables and topography. We used principal component analysis and transition probability analysis to detect associative interactions between vegetation and geomorphic variables and convergent cross-mapping on lidar data to detect causal interactions between biomass and topography. Exploratory statistics revealed that plant communities with distinct morphologies exerted control on landscape evolution through stress divergence (i.e., channel initiation) and promoting the accumulation of fine sediment in channels. Together, these communities participated in a negative feedback that maintains low energy and multiple channels. Because of the spatially explicit nature of this feedback, causal interactions could not be uncovered from convergent cross-mapping with this limited dataset, serving as a reminder that spatially explicit approaches for revealing causality are needed to reconstruct self-organizing mechanisms from data.

Models of conceptual understanding in human respiration and strategies for instruction

NASA Astrophysics Data System (ADS)

Rea-Ramirez, Mary Anne

Prior research has indicated that students of all ages show little understanding of respiration beyond breathing in and out and the need for air to survive. This occurs even after instruction with alternative conceptions persisting into adulthood. Whether this is due to specific educational strategies or to the level of difficulty in understanding a complex system is an important question. The purpose of this study was to obtain a deeper understanding of middle school students' development of mental models of human respiration. The study was composed of two major parts, one concerned with documenting and analyzing how students learn, and one concerned with measuring the effect of teaching strategies. This was carried out through a pre-test, "learning aloud" case studies in which students engaged in one-on-one tutoring interviews with the researcher, and a post-test. Transcript data from the intervention and post-test indicates that all students in this study were successful in constructing mental models of a complex concept, respiration, and in successfully applying these mental models to transfer problems. Differences in the pretest and posttest means were on the order of two standard deviations in size. While findings were uncovered in the use of a variety of strategies, possibly most interesting are the new views of analogies as an instructional strategy. Some analogies appear to be effective in supporting construction of visual/spatial features. Providing multiple, simple analogies that allow the student to construct new models in small steps, using student generated analogies, and using analogies to determine prior knowledge may also increase the effectiveness of analogies. Evidence suggested that students were able to extend the dynamic properties of certain analogies to the dynamics of the target conception and that this, in turn, allowed students to use the new models to explain causal relationships and give new function to models. This suggests that construction of causal, dynamic mental models is supported by the use of analogies containing dynamic and causal relationships.

Annual research review: Rare genotypes and childhood psychopathology--uncovering diverse developmental mechanisms of ADHD risk.

PubMed

Scerif, Gaia; Baker, Kate

2015-03-01

Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional-behavioural disturbance has theoretical and practical utility. We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses - attention deficit hyperactivity disorder (ADHD) - in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within genotype-defined groups. Crucially, as genetic predispositions modify interaction dynamics from the outset, longitudinal research is required to understand the multi-level developmental processes that mediate symptom evolution. © 2014 Association for Child and Adolescent Mental Health.

Deciphering the language of nature: cryptography, secrecy, and alterity in Francis Bacon.

PubMed

Clody, Michael C

2011-01-01

The essay argues that Francis Bacon's considerations of parables and cryptography reflect larger interpretative concerns of his natural philosophic project. Bacon describes nature as having a language distinct from those of God and man, and, in so doing, establishes a central problem of his natural philosophy—namely, how can the language of nature be accessed through scientific representation? Ultimately, Bacon's solution relies on a theory of differential and duplicitous signs that conceal within them the hidden voice of nature, which is best recognized in the natural forms of efficient causality. The "alphabet of nature"—those tables of natural occurrences—consequently plays a central role in his program, as it renders nature's language susceptible to a process and decryption that mirrors the model of the bilateral cipher. It is argued that while the writing of Bacon's natural philosophy strives for literality, its investigative process preserves a space for alterity within scientific representation, that is made accessible to those with the interpretative key.

Enhanced transformation of incidentally learned knowledge into explicit memory by dopaminergic modulation.

PubMed

Clos, Mareike; Sommer, Tobias; Schneider, Signe L; Rose, Michael

2018-01-01

During incidental learning statistical regularities are extracted from the environment without the intention to learn. Acquired implicit memory of these regularities can affect behavior in the absence of awareness. However, conscious insight in the underlying regularities can also develop during learning. Such emergence of explicit memory is an important learning mechanism that is assumed to involve prediction errors in the striatum and to be dopamine-dependent. Here we directly tested this hypothesis by manipulating dopamine levels during incidental learning in a modified serial reaction time task (SRTT) featuring a hidden regular sequence of motor responses in a placebo-controlled between-group study. Awareness for the sequential regularity was subsequently assessed using cued generation and additionally verified using free recall. The results demonstrated that dopaminergic modulation nearly doubled the amount of explicit sequence knowledge emerged during learning in comparison to the placebo group. This strong effect clearly argues for a causal role of dopamine-dependent processing for the development of awareness for sequential regularities during learning.

Retro-causation, Minimum Contradictions and Non-locality

NASA Astrophysics Data System (ADS)

Kafatos, Menas; Nassikas, Athanassios A.

2011-11-01

Retro-causation has been experimentally verified by Bem and proposed by Kafatos in the form of space-time non-locality in the quantum framework. Every theory includes, beyond its specific axioms, the principles of logical communication (logical language), through which it is defined. This communication obeys the Aristotelian logic (Classical Logic), the Leibniz Sufficient Reason Principle, and a hidden axiom, which basically states that there is anterior-posterior relationship everywhere in communication. By means of a theorem discussed here, it can be proved that the communication mentioned implies contradictory statements, which can only be transcended through silence, i.e. the absence of any statements. Moreover, the breaking of silence is meaningful through the claim for minimum contradictions, which implies the existence of both a logical and an illogical dimension; contradictions refer to causality, implying its opposite, namely retro-causation, and the anterior posterior axiom, implying space-time non-locality. The purpose of this paper is to outline a framework accounting for retro-causation, through both purely theoretical and reality based points of view.

Identifying the Factors Leading to Success: How an Innovative Science Curriculum Cultivates Student Motivation

NASA Astrophysics Data System (ADS)

Scogin, Stephen C.

2016-06-01

PlantingScience is an award-winning program recognized for its innovation and use of computer-supported scientist mentoring. Science learners work on inquiry-based experiments in their classrooms and communicate asynchronously with practicing plant scientist-mentors about the projects. The purpose of this study was to identify specific factors contributing to the program's effectiveness in engaging students. Using multiple data sources, grounded theory (Strauss and Corbin in Basics of qualitative research. Sage, Newbury Park, 1990) was used to develop a conceptual model identifying the central phenomenon, causal conditions, intervening conditions, strategies, contexts, and student outcomes of the project. Student motivation was determined to be the central phenomenon explaining the success of the program, with student empowerment, online mentor interaction, and authenticity of the scientific experiences serving as causal conditions. Teachers contributed to student motivation by giving students more freedom, challenging students to take projects deeper, encouraging, and scaffolding. Scientists contributed to student motivation by providing explanations, asking questions, encouraging, and offering themselves as partners in the inquiry process. Several positive student outcomes of the program were uncovered and included increased positivity, greater willingness to take projects deeper, better understanding of scientific concepts, and greater commitments to collaboration. The findings of this study provide relevant information on how to develop curriculum, use technology, and train practitioners and mentors to utilize strategies and actions that improve learners' motivation to engage in authentic science in the classroom.

Hidden momentum of electrons, nuclei, atoms, and molecules

NASA Astrophysics Data System (ADS)

Cameron, Robert P.; Cotter, J. P.

2018-04-01

We consider the positions and velocities of electrons and spinning nuclei and demonstrate that these particles harbour hidden momentum when located in an electromagnetic field. This hidden momentum is present in all atoms and molecules, however it is ultimately canceled by the momentum of the electromagnetic field. We point out that an electron vortex in an electric field might harbour a comparatively large hidden momentum and recognize the phenomenon of hidden hidden momentum.

Digital Life and Youth Well-being, Social Connectedness, Empathy, and Narcissism.

PubMed

James, Carrie; Davis, Katie; Charmaraman, Linda; Konrath, Sara; Slovak, Petr; Weinstein, Emily; Yarosh, Lana

2017-11-01

Youth well-being, social connectedness, and personality traits, such as empathy and narcissism, are at the crux of concerns often raised about the impacts of digital life. Understanding known impacts, and research gaps, in these areas is an important first step toward supporting media use that contributes positively to youth's happiness, life satisfaction, and prosocial attitudes and behaviors. By examining existing work addressing these issues across domains, we found that a complex interplay of individual factors, type of digital media engagement, and experiences in media contexts informs outcomes related to well-being, social connectedness, empathy, and narcissism. We argue that further research is needed to uncover how, where, when, and for whom digital media practices support positive well-being and social connectedness outcomes. Specifically, research needs to move beyond correlational studies to uncover causal connections between traits like narcissism and media use. Longitudinal studies are also needed to explore patterns of media use over time and related impacts. Further research is needed to explore how specific technologies can be designed to support positive well-being, social outcomes, and prosocial personality traits. Finally, research is needed regarding parenting, educational practices, and policies that support positive digital media use and related outcomes. Although existing research suggests that digital life has mixed potentials and effects for well-being, social connectedness, empathy, and narcissism, we provide recommendations for clinicians, policy makers, and educators in partnering with caregivers and youth to support media use that promotes positive outcomes in these areas. Copyright © 2017 by the American Academy of Pediatrics.

Identification of genes highly downregulated in pancreatic cancer through a meta-analysis of microarray datasets: implications for discovery of novel tumor-suppressor genes and therapeutic targets.

PubMed

Goonesekere, Nalin C W; Andersen, Wyatt; Smith, Alex; Wang, Xiaosheng

2018-02-01

The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC), which has a 5-year survival rate of about 7%. Recent failures of targeted therapies inhibiting kinase activity in clinical trials have highlighted the need for new approaches towards combating this deadly disease. In this study, we have identified genes that are significantly downregulated in PC, through a meta-analysis of large number of microarray datasets. We have used qRT-PCR to confirm the downregulation of selected genes in a panel of PC cell lines. This study has yielded several novel candidate tumor-suppressor genes (TSGs) including GNMT, CEL, PLA2G1B and SERPINI2. We highlight the role of GNMT, a methyl transferase associated with the methylation potential of the cell, and CEL, a lipase, as potential therapeutic targets. We have uncovered genetic links to risk factors associated with PC such as smoking and obesity. Genes important for patient survival and prognosis are also discussed, and we confirm the dysregulation of metabolic pathways previously observed in PC. While many of the genes downregulated in our dataset are associated with protein products normally produced by the pancreas for excretion, we have uncovered some genes whose downregulation appear to play a more causal role in PC. These genes will assist in providing a better understanding of the disease etiology of PC, and in the search for new therapeutic targets and biomarkers.

Enhancing cognition with video games: a multiple game training study.

PubMed

Oei, Adam C; Patterson, Michael D

2013-01-01

Previous evidence points to a causal link between playing action video games and enhanced cognition and perception. However, benefits of playing other video games are under-investigated. We examined whether playing non-action games also improves cognition. Hence, we compared transfer effects of an action and other non-action types that required different cognitive demands. We instructed 5 groups of non-gamer participants to play one game each on a mobile device (iPhone/iPod Touch) for one hour a day/five days a week over four weeks (20 hours). Games included action, spatial memory, match-3, hidden- object, and an agent-based life simulation. Participants performed four behavioral tasks before and after video game training to assess for transfer effects. Tasks included an attentional blink task, a spatial memory and visual search dual task, a visual filter memory task to assess for multiple object tracking and cognitive control, as well as a complex verbal span task. Action game playing eliminated attentional blink and improved cognitive control and multiple-object tracking. Match-3, spatial memory and hidden object games improved visual search performance while the latter two also improved spatial working memory. Complex verbal span improved after match-3 and action game training. Cognitive improvements were not limited to action game training alone and different games enhanced different aspects of cognition. We conclude that training specific cognitive abilities frequently in a video game improves performance in tasks that share common underlying demands. Overall, these results suggest that many video game-related cognitive improvements may not be due to training of general broad cognitive systems such as executive attentional control, but instead due to frequent utilization of specific cognitive processes during game play. Thus, many video game training related improvements to cognition may be attributed to near-transfer effects.

Hidden Attractors in Dynamical Systems. From Hidden Oscillations in Hilbert-Kolmogorov Aizerman, and Kalman Problems to Hidden Chaotic Attractor in Chua Circuits

NASA Astrophysics Data System (ADS)

Leonov, G. A.; Kuznetsov, N. V.

From a computational point of view, in nonlinear dynamical systems, attractors can be regarded as self-excited and hidden attractors. Self-excited attractors can be localized numerically by a standard computational procedure, in which after a transient process a trajectory, starting from a point of unstable manifold in a neighborhood of equilibrium, reaches a state of oscillation, therefore one can easily identify it. In contrast, for a hidden attractor, a basin of attraction does not intersect with small neighborhoods of equilibria. While classical attractors are self-excited, attractors can therefore be obtained numerically by the standard computational procedure. For localization of hidden attractors it is necessary to develop special procedures, since there are no similar transient processes leading to such attractors. At first, the problem of investigating hidden oscillations arose in the second part of Hilbert's 16th problem (1900). The first nontrivial results were obtained in Bautin's works, which were devoted to constructing nested limit cycles in quadratic systems, that showed the necessity of studying hidden oscillations for solving this problem. Later, the problem of analyzing hidden oscillations arose from engineering problems in automatic control. In the 50-60s of the last century, the investigations of widely known Markus-Yamabe's, Aizerman's, and Kalman's conjectures on absolute stability have led to the finding of hidden oscillations in automatic control systems with a unique stable stationary point. In 1961, Gubar revealed a gap in Kapranov's work on phase locked-loops (PLL) and showed the possibility of the existence of hidden oscillations in PLL. At the end of the last century, the difficulties in analyzing hidden oscillations arose in simulations of drilling systems and aircraft's control systems (anti-windup) which caused crashes. Further investigations on hidden oscillations were greatly encouraged by the present authors' discovery, in 2010 (for the first time), of chaotic hidden attractor in Chua's circuit. This survey is dedicated to efficient analytical-numerical methods for the study of hidden oscillations. Here, an attempt is made to reflect the current trends in the synthesis of analytical and numerical methods.

Shank3 mutant mice display autistic-like behaviours and striatal dysfunction

PubMed Central

Peça, João; Feliciano, Cátia; Ting, Jonathan T.; Wang, Wenting; Wells, Michael F.; Venkatraman, Talaignair N.; Lascola, Christopher D.; Fu, Zhanyan; Feng, Guoping

2011-01-01

Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. Shank3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for development of 22q13 deletion syndrome (Phelan-McDermid Syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for Shank3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic like-behaviours in mice. PMID:21423165

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice.

PubMed

Wang, I-Ting Judy; Allen, Megan; Goffin, Darren; Zhu, Xinjian; Fairless, Andrew H; Brodkin, Edward S; Siegel, Steve J; Marsh, Eric D; Blendy, Julie A; Zhou, Zhaolan

2012-12-26

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKT-mammalian target of rapamycin (mTOR) cascade, upon Cdkl5 loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for Cdkl5 loss-of-function in neurodevelopmental disorders.

Investigation of a light fixture fire

DOE PAGES

Jurney, James D.; Cournoyer, Michael E.; Trujillo, Stanley; ...

2016-04-16

Metal-halide lamps produce light by discharging an electric arc through a gaseous mixture of vaporized mercury and metal halides. Metal-halide lamps for use in spaces with lower mounting heights can produce excessive visual glare in the normal, higher field-of-view unless they are equipped with prismatic lenses. Should the bulb fail, high internal operating pressure of the arc tube can launch fragments of arc tube at high velocity in all directions, striking the outer bulb of the lamp with enough force to cause the outer bulb to break. This article reports an investigation of a light fixture fire and reviews amore » case study of a metal-halide lamp fire. We reported on causal analysis of the metal-halide lamp fire uncovered contributing factors that created the environment in which the incident occurred. Latent organizational conditions that created error-likely situations or weakened defenses were identified and controlled. Lastly, effective improvements that reduce the probability or consequence of similar metal-halide lamp fire incidents were implemented.« less

Cross-Population Joint Analysis of eQTLs: Fine Mapping and Functional Annotation

PubMed Central

Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

2015-01-01

Mapping expression quantitative trait loci (eQTLs) has been shown as a powerful tool to uncover the genetic underpinnings of many complex traits at molecular level. In this paper, we present an integrative analysis approach that leverages eQTL data collected from multiple population groups. In particular, our approach effectively identifies multiple independent cis-eQTL signals that are consistent across populations, accounting for population heterogeneity in allele frequencies and linkage disequilibrium patterns. Furthermore, by integrating genomic annotations, our analysis framework enables high-resolution functional analysis of eQTLs. We applied our statistical approach to analyze the GEUVADIS data consisting of samples from five population groups. From this analysis, we concluded that i) jointly analysis across population groups greatly improves the power of eQTL discovery and the resolution of fine mapping of causal eQTL ii) many genes harbor multiple independent eQTLs in their cis regions iii) genetic variants that disrupt transcription factor binding are significantly enriched in eQTLs (p-value = 4.93 × 10-22). PMID:25906321

Genetic identification of a common collagen disease in Puerto Ricans via identity-by-descent mapping in a health system

PubMed Central

Belbin, Gillian Morven; Odgis, Jacqueline; Sorokin, Elena P; Yee, Muh-Ching; Kohli, Sumita; Glicksberg, Benjamin S; Gignoux, Christopher R; Wojcik, Genevieve L; Van Vleck, Tielman; Jeff, Janina M; Linderman, Michael; Schurmann, Claudia; Ruderfer, Douglas; Cai, Xiaoqiang; Merkelson, Amanda; Justice, Anne E; Young, Kristin L; Graff, Misa; North, Kari E; Peters, Ulrike; James, Regina; Hindorff, Lucia; Kornreich, Ruth; Edelmann, Lisa; Gottesman, Omri; Stahl, Eli EA; Cho, Judy H; Loos, Ruth JF; Bottinger, Erwin P; Nadkarni, Girish N; Abul-Husn, Noura S

2017-01-01

Achieving confidence in the causality of a disease locus is a complex task that often requires supporting data from both statistical genetics and clinical genomics. Here we describe a combined approach to identify and characterize a genetic disorder that leverages distantly related patients in a health system and population-scale mapping. We utilize genomic data to uncover components of distant pedigrees, in the absence of recorded pedigree information, in the multi-ethnic BioMe biobank in New York City. By linking to medical records, we discover a locus associated with both elevated genetic relatedness and extreme short stature. We link the gene, COL27A1, with a little-known genetic disease, previously thought to be rare and recessive. We demonstrate that disease manifests in both heterozygotes and homozygotes, indicating a common collagen disorder impacting up to 2% of individuals of Puerto Rican ancestry, leading to a better understanding of the continuum of complex and Mendelian disease. PMID:28895531

A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of WDR45.

PubMed

Hermann, Andreas; Kitzler, Hagen H; Pollack, Tobias; Biskup, Saskia; Krüger, Stefanie; Funke, Claudia; Terrile, Caterina; Haack, Tobias B

2017-01-01

Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45 . An initial gene panel and Sanger sequencing approach failed to uncover the molecular defect. Based on the typical clinical and neuroimaging phenotype, quantitative polymerase chain reaction of the WDR45 coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls. An extended search for deletions should be performed in apparently WDR45- negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia.

Towards the map of quantum gravity

NASA Astrophysics Data System (ADS)

Mielczarek, Jakub; Trześniewski, Tomasz

2018-06-01

In this paper we point out some possible links between different approaches to quantum gravity and theories of the Planck scale physics. In particular, connections between loop quantum gravity, causal dynamical triangulations, Hořava-Lifshitz gravity, asymptotic safety scenario, Quantum Graphity, deformations of relativistic symmetries and nonlinear phase space models are discussed. The main focus is on quantum deformations of the Hypersurface Deformations Algebra and Poincaré algebra, nonlinear structure of phase space, the running dimension of spacetime and nontrivial phase diagram of quantum gravity. We present an attempt to arrange the observed relations in the form of a graph, highlighting different aspects of quantum gravity. The analysis is performed in the spirit of a mind map, which represents the architectural approach to the studied theory, being a natural way to describe the properties of a complex system. We hope that the constructed graphs (maps) will turn out to be helpful in uncovering the global picture of quantum gravity as a particular complex system and serve as a useful guide for the researchers.

Experimental Myocardial Infarction Upregulates Circulating Fibroblast Growth Factor-23.

PubMed

Andrukhova, Olena; Slavic, Svetlana; Odörfer, Kathrin I; Erben, Reinhold G

2015-10-01

Myocardial infarction (MI) is a major cause of death worldwide. Epidemiological studies have linked vitamin D deficiency to MI incidence. Because fibroblast growth factor-23 (FGF23) is a master regulator of vitamin D hormone production and has been shown to be associated with cardiac hypertrophy per se, we explored the hypothesis that FGF23 may be a previously unrecognized pathophysiological factor causally linked to progression of cardiac dysfunction post-MI. Here, we show that circulating intact Fgf23 was profoundly elevated, whereas serum vitamin D hormone levels were suppressed, after induction of experimental MI in rat and mouse models, independent of changes in serum soluble Klotho or serum parathyroid hormone. Both skeletal and cardiac expression of Fgf23 was increased after MI. Although the molecular link between the cardiac lesion and circulating Fgf23 concentrations remains to be identified, our study has uncovered a novel heart-bone-kidney axis that may have important clinical implications and may inaugurate the new field of cardio-osteology. © 2015 American Society for Bone and Mineral Research.

Disparity channels in early vision

PubMed Central

Roe, AW; Parker, AJ; Born, RT; DeAngelis, GC

2008-01-01

The last decade has seen a dramatic increase in our knowledge of the neural basis of stereopsis. New cortical areas have been found to represent binocular disparities, new representations of disparity information (e.g., relative disparity signals) have been uncovered, the first topographic maps of disparity have been measured, and the first causal links between neural activity and depth perception have been established. Equally exciting is the finding that training and experience affects how signals are channeled through different brain areas, a flexibility that may be crucial for learning, plasticity, and recovery of function. The collective efforts of several laboratories have established stereo vision as one of the most productive model systems for elucidating the neural basis of perception. Much remains to be learned about how the disparity signals that are initially encoded in primary visual cortex are routed to and processed by extrastriate areas to mediate the diverse capacities of 3D vision that enhance our daily experience of the world. PMID:17978018

Investigation of a light fixture fire

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jurney, James D.; Cournoyer, Michael E.; Trujillo, Stanley

Metal-halide lamps produce light by discharging an electric arc through a gaseous mixture of vaporized mercury and metal halides. Metal-halide lamps for use in spaces with lower mounting heights can produce excessive visual glare in the normal, higher field-of-view unless they are equipped with prismatic lenses. Should the bulb fail, high internal operating pressure of the arc tube can launch fragments of arc tube at high velocity in all directions, striking the outer bulb of the lamp with enough force to cause the outer bulb to break. This article reports an investigation of a light fixture fire and reviews amore » case study of a metal-halide lamp fire. We reported on causal analysis of the metal-halide lamp fire uncovered contributing factors that created the environment in which the incident occurred. Latent organizational conditions that created error-likely situations or weakened defenses were identified and controlled. Lastly, effective improvements that reduce the probability or consequence of similar metal-halide lamp fire incidents were implemented.« less

Integrating Insults: Using Fault Tree Analysis to Guide Schizophrenia Research across Levels of Analysis.

PubMed

MacDonald Iii, Angus W; Zick, Jennifer L; Chafee, Matthew V; Netoff, Theoden I

2015-01-01

The grand challenges of schizophrenia research are linking the causes of the disorder to its symptoms and finding ways to overcome those symptoms. We argue that the field will be unable to address these challenges within psychiatry's standard neo-Kraepelinian (DSM) perspective. At the same time the current corrective, based in molecular genetics and cognitive neuroscience, is also likely to flounder due to its neglect for psychiatry's syndromal structure. We suggest adopting a new approach long used in reliability engineering, which also serves as a synthesis of these approaches. This approach, known as fault tree analysis, can be combined with extant neuroscientific data collection and computational modeling efforts to uncover the causal structures underlying the cognitive and affective failures in people with schizophrenia as well as other complex psychiatric phenomena. By making explicit how causes combine from basic faults to downstream failures, this approach makes affordances for: (1) causes that are neither necessary nor sufficient in and of themselves; (2) within-diagnosis heterogeneity; and (3) between diagnosis co-morbidity.

Illicit Drug Use Among South Korean Offenders: Assessing the Generality of Social Learning Theory.

PubMed

Yun, Minwoo; Kim, Eunyoung

2015-10-01

Since the mid-1990s, illicit drug use has become a problem in Korean society. This trend is likely due to the rapid globalization and expansion that occurred with the Internet revolution, which led to greater numbers of people socially learning about drug culture. The current study attempts to uncover criminogenic causality of such social learning about drug use by studying adult felony drug offenders in South Korea. The data used for the study were obtained from self-reported surveys, originally collected by the Korean Institution of Criminology (KIC). The final sample comprised 1,452 felony offenders convicted of illicit drug use, and their responses were analyzed with a set of multiple logistic regression tests. The current study found supportive evidence for the generalizability of social learning theory from the sample of the South Korean adult drug offenders. We argue that the current study provides additional empirical evidence that supports the generalizability of social learning theory. © The Author(s) 2014.

Comparing lagged linear correlation, lagged regression, Granger causality, and vector autoregression for uncovering associations in EHR data.

PubMed

Levine, Matthew E; Albers, David J; Hripcsak, George

2016-01-01

Time series analysis methods have been shown to reveal clinical and biological associations in data collected in the electronic health record. We wish to develop reliable high-throughput methods for identifying adverse drug effects that are easy to implement and produce readily interpretable results. To move toward this goal, we used univariate and multivariate lagged regression models to investigate associations between twenty pairs of drug orders and laboratory measurements. Multivariate lagged regression models exhibited higher sensitivity and specificity than univariate lagged regression in the 20 examples, and incorporating autoregressive terms for labs and drugs produced more robust signals in cases of known associations among the 20 example pairings. Moreover, including inpatient admission terms in the model attenuated the signals for some cases of unlikely associations, demonstrating how multivariate lagged regression models' explicit handling of context-based variables can provide a simple way to probe for health-care processes that confound analyses of EHR data.

The secret art of managing healthcare expenses: investigating implicit rationing and autonomy in public healthcare systems.

PubMed

Lauridsen, S M R; Norup, M S; Rossel, P J H

2007-12-01

Rationing healthcare is a difficult task, which includes preventing patients from accessing potentially beneficial treatments. Proponents of implicit rationing argue that politicians cannot resist pressure from strong patient groups for treatments and conclude that physicians should ration without informing patients or the public. The authors subdivide this specific programme of implicit rationing, or "hidden rationing", into local hidden rationing, unsophisticated global hidden rationing and sophisticated global hidden rationing. They evaluate the appropriateness of these methods of rationing from the perspectives of individual and political autonomy and conclude that local hidden rationing and unsophisticated global hidden rationing clearly violate patients' individual autonomy, that is, their right to participate in medical decision-making. While sophisticated global hidden rationing avoids this charge, the authors point out that it nonetheless violates the political autonomy of patients, that is, their right to engage in public affairs as citizens. A defence of any of the forms of hidden rationing is therefore considered to be incompatible with a defence of autonomy.

Follow that fish: Uncovering the hidden blue economy in coral reef fisheries.

PubMed

Grafeld, Shanna; Oleson, Kirsten L L; Teneva, Lida; Kittinger, John N

2017-01-01

Despite their importance for human well-being, nearshore fisheries are often data poor, undervalued, and underappreciated in policy and development programs. We assess the value chain for nearshore Hawaiian coral reef fisheries, mapping post-catch distribution and disposition, and quantifying associated monetary, food security, and cultural values. We estimate that the total annual value of the nearshore fishery in Hawai'i is $10.3-$16.4 million, composed of non-commercial ($7.2-$12.9 million) and commercial ($2.97 million licensed + $148,500-$445,500 unlicensed) catch. Hawaii's nearshore fisheries provide >7 million meals annually, with most (>5 million) from the non-commercial sector. Over a third (36%) of meals were planktivores, 26% piscivores, 21% primary consumers, and 18% secondary consumers. Only 62% of licensed commercial catch is accounted for in purchase reports, leaving 38% of landings unreported in sales. Value chains are complex, with major buyers for the commercial fishery including grocery stores (66%), retailers (19%), wholesalers (14%), and restaurants (<1%), who also trade and sell amongst themselves. The bulk of total nearshore catch (72-74%) follows a short value chain, with non-commercial fishers keeping catch for household consumption or community sharing. A small amount (~37,000kg) of reef fish-the equivalent of 1.8% of local catch-is imported annually into Hawai'i, 23,000kg of which arrives as passenger luggage on commercial flights from Micronesia. Evidence of exports to the US mainland exists, but is unquantifiable given existing data. Hawaiian nearshore fisheries support fundamental cultural values including subsistence, activity, traditional knowledge, and social cohesion. These small-scale coral reef fisheries provide large-scale benefits to the economy, food security, and cultural practices of Hawai'i, underscoring the need for sustainable management. This research highlights the value of information on the value chain for small-scale production systems, making the hidden economy of these fisheries visible and illuminating a range of conservation interventions applicable to Hawai'i and beyond.

Application of dynamic topic models to toxicogenomics data.

PubMed

Lee, Mikyung; Liu, Zhichao; Huang, Ruili; Tong, Weida

2016-10-06

All biological processes are inherently dynamic. Biological systems evolve transiently or sustainably according to sequential time points after perturbation by environment insults, drugs and chemicals. Investigating the temporal behavior of molecular events has been an important subject to understand the underlying mechanisms governing the biological system in response to, such as, drug treatment. The intrinsic complexity of time series data requires appropriate computational algorithms for data interpretation. In this study, we propose, for the first time, the application of dynamic topic models (DTM) for analyzing time-series gene expression data. A large time-series toxicogenomics dataset was studied. It contains over 3144 microarrays of gene expression data corresponding to rat livers treated with 131 compounds (most are drugs) at two doses (control and high dose) in a repeated schedule containing four separate time points (4-, 8-, 15- and 29-day). We analyzed, with DTM, the topics (consisting of a set of genes) and their biological interpretations over these four time points. We identified hidden patterns embedded in this time-series gene expression profiles. From the topic distribution for compound-time condition, a number of drugs were successfully clustered by their shared mode-of-action such as PPARɑ agonists and COX inhibitors. The biological meaning underlying each topic was interpreted using diverse sources of information such as functional analysis of the pathways and therapeutic uses of the drugs. Additionally, we found that sample clusters produced by DTM are much more coherent in terms of functional categories when compared to traditional clustering algorithms. We demonstrated that DTM, a text mining technique, can be a powerful computational approach for clustering time-series gene expression profiles with the probabilistic representation of their dynamic features along sequential time frames. The method offers an alternative way for uncovering hidden patterns embedded in time series gene expression profiles to gain enhanced understanding of dynamic behavior of gene regulation in the biological system.

Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.

PubMed

Keogh, Ruth; Frost, Chris; Owen, Gail; Daniel, Rhian M; Langbehn, Doug R; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Landwehrmeyer, G Bernhard; Reilmann, Ralf; Borowsky, Beth; Stout, Julie; Craufurd, David; Tabrizi, Sarah J

2016-01-11

 Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.

Inferring causal genomic alterations in breast cancer using gene expression data

PubMed Central

2011-01-01

Background One of the primary objectives in cancer research is to identify causal genomic alterations, such as somatic copy number variation (CNV) and somatic mutations, during tumor development. Many valuable studies lack genomic data to detect CNV; therefore, methods that are able to infer CNVs from gene expression data would help maximize the value of these studies. Results We developed a framework for identifying recurrent regions of CNV and distinguishing the cancer driver genes from the passenger genes in the regions. By inferring CNV regions across many datasets we were able to identify 109 recurrent amplified/deleted CNV regions. Many of these regions are enriched for genes involved in many important processes associated with tumorigenesis and cancer progression. Genes in these recurrent CNV regions were then examined in the context of gene regulatory networks to prioritize putative cancer driver genes. The cancer driver genes uncovered by the framework include not only well-known oncogenes but also a number of novel cancer susceptibility genes validated via siRNA experiments. Conclusions To our knowledge, this is the first effort to systematically identify and validate drivers for expression based CNV regions in breast cancer. The framework where the wavelet analysis of copy number alteration based on expression coupled with the gene regulatory network analysis, provides a blueprint for leveraging genomic data to identify key regulatory components and gene targets. This integrative approach can be applied to many other large-scale gene expression studies and other novel types of cancer data such as next-generation sequencing based expression (RNA-Seq) as well as CNV data. PMID:21806811

The Hidden Curriculum as Emancipatory and Non-Emancipatory Tools.

ERIC Educational Resources Information Center

Kanpol, Barry

Moral values implied in school practices and policies constitute the "hidden curriculum." Because the hidden curriculum may promote certain moral values to students, teachers are partially responsible for the moral education of students. A component of the hidden curriculum, institutional political resistance, concerns teacher opposition to…

Multiple capacitors for natural genetic variation in Drosophila melanogaster.

PubMed

Takahashi, Kazuo H

2013-03-01

Cryptic genetic variation (CGV) or a standing genetic variation that is not ordinarily expressed as a phenotype is released when the robustness of organisms is impaired under environmental or genetic perturbations. Evolutionary capacitors modulate the amount of genetic variation exposed to natural selection and hidden cryptically; they have a fundamental effect on the evolvability of traits on evolutionary timescales. In this study, I have demonstrated the effects of multiple genomic regions of Drosophila melanogaster on CGV in wing shape. I examined the effects of 61 genomic deficiencies on quantitative and qualitative natural genetic variation in the wing shape of D. melanogaster. I have identified 10 genomic deficiencies that do not encompass a known candidate evolutionary capacitor, Hsp90, exposing natural CGV differently depending on the location of the deficiencies in the genome. Furthermore, five genomic deficiencies uncovered qualitative CGV in wing morphology. These findings suggest that CGV in wing shape of wild-type D. melanogaster is regulated by multiple capacitors with divergent functions. Future analysis of genes encompassed by these genomic regions would help elucidate novel capacitor genes and better understand the general features of capacitors regarding natural genetic variation. © 2012 Blackwell Publishing Ltd.

Toward Systems Metabolic Engineering of Streptomycetes for Secondary Metabolites Production.

PubMed

Robertsen, Helene Lunde; Weber, Tilmann; Kim, Hyun Uk; Lee, Sang Yup

2018-01-01

Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical trials in the last decades. A paradigm shift took place when the first whole genome sequences of streptomycetes became available, from which silent or "cryptic" biosynthetic gene clusters (BGCs) were discovered. Cryptic BGCs reveal a so far untapped potential of the microorganisms for the production of novel compounds, which has spurred new efforts in understanding the complex regulation between primary and secondary metabolism. This new trend has been accompanied with development of new computational resources (genome and compound mining tools), generation of various high-quality omics data, establishment of molecular tools, and other strain engineering strategies. They all come together to enable systems metabolic engineering of streptomycetes, allowing more systematic and efficient strain development. In this review, the authors present recent progresses within systems metabolic engineering of streptomycetes for uncovering their hidden potential to produce novel compounds and for the improved production of secondary metabolites. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Signatures of AGN feedback

NASA Astrophysics Data System (ADS)

Wylezalek, Dominika; Zakamska, Nadia L.; MaNGA-GMOS Team

2017-01-01

Feedback from actively accreting SMBHs (Active Galactic Nuclei, AGN) is now widely considered to be the main driver in regulating the growth of massive galaxies. Observational proof for this scenario has, however, been hard to come by. Many attempts at finding a conclusive observational proof that AGN may be able to quench star formation and regulate the host galaxies' growth have shown that this problem is highly complex.I will present results from several projects that focus on understanding the power, reach and impact of feedback processes exerted by AGN. I will describe recent efforts in our group of relating feedback signatures to the specific star formation rate in their host galaxies, where our results are consistent with the AGN having a `negative' impact through feedback on the galaxies' star formation history (Wylezalek+2016a,b). Furthermore, I will show that powerful AGN-driven winds can be easily hidden and not be apparent in the integrated spectrum of the galaxy. This implies that large IFU surveys, such as the SDSS-IV MaNGA survey, might uncover many previously unknown AGN and outflows that are potentially very relevant for understanding the role of AGN in galaxy evolution (Wylezalek+2016c)!

Flavor structure of the cosmic-ray electron/positron excesses at DAMPE

NASA Astrophysics Data System (ADS)

Ge, Shao-Feng; He, Hong-Jian; Wang, Yu-Chen

2018-06-01

The Dark Matter Particle Explorer (DAMPE) satellite detector announced its first result for measuring the cosmic-ray electron/positron (CRE) energy spectrum up to 4.6 TeV, including a tentative peak-like event excess at (1.3-1.5) TeV. In this work, we uncover a significant hidden excess in the DAMPE CRE spectrum over the energy range (0.6-1.1) TeV, which has a non-peak-like structure. We propose a new mechanism to explain this excess by a set of 1.5 TeV μ± events with subsequent decays into e± plus neutrinos. For explaining this new excess together with the peak excess around 1.4 TeV, we demonstrate that the flavor structure of the original lepton final-state produced by dark matter (DM) annihilations (or other mechanism) should have a composition ratio Ne : (Nμ + 1/6 Nτ) = 1 : y, with y ≃ 2.6- 10.8. For lepton portal DM models, this puts nontrivial constraint on the lepton-DM-mediator couplings λe : (λμ4 + 1/6 λτ4) 1/4 = 1 : y1/4 with a narrow range y1/4 ≃ 1.3- 1.8.

Energy dissipation in quasi-linear viscoelastic tissues, cells, and extracellular matrix.

PubMed

Babaei, Behzad; Velasquez-Mao, A J; Pryse, Kenneth M; McConnaughey, William B; Elson, Elliot L; Genin, Guy M

2018-05-21

Characterizing how a tissue's constituents give rise to its viscoelasticity is important for uncovering how hidden timescales underlie multiscale biomechanics. These constituents are viscoelastic in nature, and their mechanics must typically be assessed from the uniaxial behavior of a tissue. Confounding the challenge is that tissue viscoelasticity is typically associated with nonlinear elastic responses. Here, we experimentally assessed how fibroblasts and extracellular matrix (ECM) within engineered tissue constructs give rise to the nonlinear viscoelastic responses of a tissue. We applied a constant strain rate, "triangular-wave" loading and interpreted responses using the Fung quasi-linear viscoelastic (QLV) material model. Although the Fung QLV model has several well-known weaknesses, it was well suited to the behaviors of the tissue constructs, cells, and ECM tested. Cells showed relatively high damping over certain loading frequency ranges. Analysis revealed that, even in cases where the Fung QLV model provided an excellent fit to data, the the time constant derived from the model was not in general a material parameter. Results have implications for design of protocols for the mechanical characterization of biological materials, and for the mechanobiology of cells within viscoelastic tissues. Copyright © 2018. Published by Elsevier Ltd.

Photoacoustic imaging of hidden dental caries by using a fiber-based probing system

NASA Astrophysics Data System (ADS)

Koyama, Takuya; Kakino, Satoko; Matsuura, Yuji

2017-04-01

Photoacoustic method to detect hidden dental caries is proposed. It was found that high frequency ultrasonic waves are generated from hidden carious part when radiating laser light to occlusal surface of model tooth. By making a map of intensity of these high frequency components, photoacoustic images of hidden caries were successfully obtained. A photoacoustic imaging system using a bundle of hollow optical fiber was fabricated for using clinical application, and clear photoacoustic image of hidden caries was also obtained by this system.

--No Title--

Science.gov Websites

;height:auto;overflow:hidden}.poc_table .top_row{background-color:#eee;height:auto;overflow:hidden}.poc_table ;background-color:#FFF;height:auto;overflow:hidden;border-top:1px solid #ccc}.poc_table .main_row .name :200px;padding:5px;height:auto;overflow:hidden}.tli_grey_box{background-color:#eaeaea;text-align:center

Natural hidden antibodies reacting with DNA or cardiolipin bind to thymocytes and evoke their death.

PubMed

Zamulaeva, I A; Lekakh, I V; Kiseleva, V I; Gabai, V L; Saenko, A S; Shevchenko, A S; Poverenny, A M

1997-08-18

Both free and hidden natural antibodies to DNA or cardiolipin were obtained from immunoglobulins of a normal donor. The free antibodies reacting with DNA or cardiolipin were isolated by means of affinity chromatography. Antibodies occurring in an hidden state were disengaged from the depleted immunoglobulins by ion-exchange chromatography and were then affinity-isolated on DNA or cardiolipin sorbents. We used flow cytometry to study the ability of free and hidden antibodies to bind to rat thymocytes. Simultaneously, plasma membrane integrity was tested by propidium iodide (PI) exclusion. The hidden antibodies reacted with 65.2 +/- 10.9% of the thymocytes and caused a fast plasma membrane disruption. Cells (28.7 +/- 7.1%) were stained with PI after incubation with the hidden antibodies for 1 h. The free antibodies bound to a very small fraction of the thymocytes and did not evoke death as compared to control without antibodies. The possible reason for the observed effects is difference in reactivity of the free and hidden antibodies to phospholipids. While free antibodies reacted preferentially with phosphotidylcholine, hidden antibodies reacted with cardiolipin and phosphotidylserine.

Raising awareness of the hidden curriculum in veterinary medical education: a review and call for research.

PubMed

Whitcomb, Tiffany L

2014-01-01

The hidden curriculum is characterized by information that is tacitly conveyed to and among students about the cultural and moral environment in which they find themselves. Although the hidden curriculum is often defined as a distinct entity, tacit information is conveyed to students throughout all aspects of formal and informal curricula. This unconsciously communicated knowledge has been identified across a wide spectrum of educational environments and is known to have lasting and powerful impacts, both positive and negative. Recently, medical education research on the hidden curriculum of becoming a doctor has come to the forefront as institutions struggle with inconsistencies between formal and hidden curricula that hinder the practice of patient-centered medicine. Similarly, the complex ethical questions that arise during the practice and teaching of veterinary medicine have the potential to cause disagreement between what the institution sets out to teach and what is actually learned. However, the hidden curriculum remains largely unexplored for this field. Because the hidden curriculum is retained effectively by students, elucidating its underlying messages can be a key component of program refinement. A review of recent literature about the hidden curriculum in a variety of fields, including medical education, will be used to explore potential hidden curricula in veterinary medicine and draw attention to the need for further investigation.

EPR paradox, quantum nonlocality and physical reality

NASA Astrophysics Data System (ADS)

Kupczynski, M.

2016-03-01

Eighty years ago Einstein, Podolsky and Rosen demonstrated that instantaneous reduction of wave function, believed to describe completely a pair of entangled physical systems, led to EPR paradox. The paradox disappears in statistical interpretation of quantum mechanics (QM) according to which a wave function describes only an ensemble of identically prepared physical systems. QM predicts strong correlations between outcomes of measurements performed on different members of EPR pairs in far-away locations. Searching for an intuitive explanation of these correlations John Bell analysed so called local realistic hidden variable models and proved that correlations consistent with these models satisfy Bell inequalities which are violated by some predictions of QM and by experimental data. Several different local models were constructed and inequalities proven. Some eminent physicists concluded that Nature is definitely nonlocal and that it is acting according to a law of nonlocal randomness. According to these law perfectly random, but strongly correlated events, can be produced at the same time in far away locations and a local and causal explanation of their occurrence cannot be given. We strongly disagree with this conclusion and we prove the contrary by analysing in detail some influential finite sample proofs of Bell and CHSH inequalities and so called Quantum Randi Challenges. We also show how one can win so called Bell's game without violating locality of Nature. Nonlocal randomness is inconsistent with local quantum field theory, with standard model in elementary particle physics and with causal laws and adaptive dynamics prevailing in the surrounding us world. The experimental violation of Bell-type inequalities does not prove the nonlocality of Nature but it only confirms a contextual character of quantum observables and gives a strong argument against counterfactual definiteness and against a point of view according to which experimental outcomes are produced in irreducible random way.

The two time vectors of Nachträglichkeit in the development of ego organization: significance of the concept for the symbolization of nameless traumas and anxieties.

PubMed

Dahl, Gerhard

2010-08-01

The author describes Freud 's conception of Nachträglichkeit as an active process that bridges the gap between past affective vicissitudes and the cognitive present by way of meaning. Symbolization is thereby subsequently [nachträglich] conferred on early traumatic events, which thus become susceptible to omnipotent control. The two time vectors of Nachträglichkeit are discussed: the first is a causal process operating in the forward direction of time against the background of a factual reality, while the second is a backward movement that permits an understanding of unconscious scenes and phantasies taking place at primary-process level. This twofold temporal motion was observed and described by Freud early on. However, its significance often remained hidden prior to his study of Moses. It was mostly overlooked in English and French translations, thus giving rise to a one-sided understanding of the concept in the various psychoanalytic cultures, as either deferred action or après-coup. Freud 's Moses study addresses both temporal aspects of Nachträglichkeit, seeking not only to reconstruct a past event on a causal, deterministic basis, but also to understand the subjective truth of that event in the transference along the retrograde time line. The decisive criterion for the conceptual and clinical separation of the two time vectors is the development of ego organization and the capacity for symbolization. The two vectors should not be separated on the factual level, as both aspects of Nachträglichkeit are essential to the understanding of unconscious processes, combining as they do in a relationship of circular complementarity. © 2009 Institute of Psychoanalysis.

Differentiability of correlations in realistic quantum mechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cabrera, Alejandro; Faria, Edson de; Pujals, Enrique

2015-09-15

We prove a version of Bell’s theorem in which the locality assumption is weakened. We start by assuming theoretical quantum mechanics and weak forms of relativistic causality and of realism (essentially the fact that observable values are well defined independently of whether or not they are measured). Under these hypotheses, we show that only one of the correlation functions that can be formulated in the framework of the usual Bell theorem is unknown. We prove that this unknown function must be differentiable at certain angular configuration points that include the origin. We also prove that, if this correlation is assumedmore » to be twice differentiable at the origin, then we arrive at a version of Bell’s theorem. On the one hand, we are showing that any realistic theory of quantum mechanics which incorporates the kinematic aspects of relativity must lead to this type of rough correlation function that is once but not twice differentiable. On the other hand, this study brings us a single degree of differentiability away from a relativistic von Neumann no hidden variables theorem.« less

Dealing with quantum weirdness: Holism and related issues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elby, Andrew Richard

1995-12-01

Various issues are discussed in interpretation of quantum mechanics. All these explorations point toward the same conclusion, that some systems are holistically connected, i.e., some composite systems have properties that cannot, even in principle, be reduced to the properties of its subsystems. This is argued to be the central metaphysical lesson of quantum theory; this will remain pertinent even if quantum mechanics gets replaced by a superior theory. Chap. 2 discusses nonlocality and rules out hidden-variable theories that approximately reproduce the perfect correlations of quantum mechanics, as well as theories that obey locality conditions weaker than those needed to derivemore » Bell`s inequality. Chap. 3 shows that SQUID experiments can rule out non-invasive measurability if not macrorealism. Chap. 4 looks at interpretational issues surrounding decoherence, the dissipative interaction between a system and its environment. Decoherence klcan help ``modal`` interpretations pick out the desired ``preferred`` basis. Chap. 5 explores what varieties of causation can and cannot ``explain`` EPR correlations. Instead of relying on ``watered down`` causal explanations, we should instead develop new, holistic explanatory frameworks.« less

Extending quantum mechanics entails extending special relativity

NASA Astrophysics Data System (ADS)

Aravinda, S.; Srikanth, R.

2016-05-01

The complementarity between signaling and randomness in any communicated resource that can simulate singlet statistics is generalized by relaxing the assumption of free will in the choice of measurement settings. We show how to construct an ontological extension for quantum mechanics (QMs) through the oblivious embedding of a sound simulation protocol in a Newtonian spacetime. Minkowski or other intermediate spacetimes are ruled out as the locus of the embedding by virtue of hidden influence inequalities. The complementarity transferred from a simulation to the extension unifies a number of results about quantum non-locality, and implies that special relativity has a different significance for the ontological model and for the operational theory it reproduces. Only the latter, being experimentally accessible, is required to be Lorentz covariant. There may be certain Lorentz non-covariant elements at the ontological level, but they will be inaccessible at the operational level in a valid extension. Certain arguments against the extendability of QM, due to Conway and Kochen (2009) and Colbeck and Renner (2012), are attributed to their assumption that the spacetime at the ontological level has Minkowski causal structure.

Quantum Locality, Rings a Bell?: Bell's Inequality Meets Local Reality and True Determinism

NASA Astrophysics Data System (ADS)

Sánchez-Kuntz, Natalia; Nahmad-Achar, Eduardo

2018-01-01

By assuming a deterministic evolution of quantum systems and taking realism into account, we carefully build a hidden variable theory for Quantum Mechanics (QM) based on the notion of ontological states proposed by 't Hooft (The cellular automaton interpretation of quantum mechanics, arXiv:1405.1548v3, 2015; Springer Open 185, https://doi.org/10.1007/978-3-319-41285-6, 2016). We view these ontological states as the ones embedded with realism and compare them to the (usual) quantum states that represent superpositions, viewing the latter as mere information of the system they describe. Such a deterministic model puts forward conditions for the applicability of Bell's inequality: the usual inequality cannot be applied to the usual experiments. We build a Bell-like inequality that can be applied to the EPR scenario and show that this inequality is always satisfied by QM. In this way we show that QM can indeed have a local interpretation, and thus meet with the causal structure imposed by the Theory of Special Relativity in a satisfying way.

Development of young children's understanding that the recent past is causally bound to the present.

PubMed

Povinelli, D J; Landry, A M; Theall, L A; Clark, B R; Castille, C M

1999-11-01

The results of 6 studies (involving 304 children) suggested that 4- and 5-year-olds, but not 3-year-olds, understand that very recent past events determine the present. In Studies 1-3, 3- and 4-year-old children were introduced to 2 empty hiding locations. With children's backs to these locations, a camera recorded an experimenter secretly hiding a puppet in one of them. Children then viewed the videotape of what had just happened, along with another tape that depicted identical events except with a different child and with the puppet hidden in the other location. Only 4-year-olds were subsequently able to locate the puppet, even though 3-year-olds remembered the contents of the tapes and understood the equivalence between the video events and the real world. In Study 4, similar effects were obtained when a verbal analog of the test was presented to 3-5-year-olds. Studies 5 and 6 showed that when children observed 2 events in which they had just participated, only 5-year-olds understood that the most recent events were relevant.

Vegetation anomalies caused by antecedent precipitation in most of the world

NASA Astrophysics Data System (ADS)

Papagiannopoulou, C.; Miralles, D. G.; Dorigo, W. A.; Verhoest, N. E. C.; Depoorter, M.; Waegeman, W.

2017-07-01

Quantifying environmental controls on vegetation is critical to predict the net effect of climate change on global ecosystems and the subsequent feedback on climate. Following a non-linear Granger causality framework based on a random forest predictive model, we exploit the current wealth of multi-decadal satellite data records to uncover the main drivers of monthly vegetation variability at the global scale. Results indicate that water availability is the most dominant factor driving vegetation globally: about 61% of the vegetated surface was primarily water-limited during 1981-2010. This included semiarid climates but also transitional ecoregions. Intra-annually, temperature controls Northern Hemisphere deciduous forests during the growing season, while antecedent precipitation largely dominates vegetation dynamics during the senescence period. The uncovered dependency of global vegetation on water availability is substantially larger than previously reported. This is owed to the ability of the framework to (1) disentangle the co-linearities between radiation/temperature and precipitation, and (2) quantify non-linear impacts of climate on vegetation. Our results reveal a prolonged effect of precipitation anomalies in dry regions: due to the long memory of soil moisture and the cumulative, non-linear, response of vegetation, water-limited regions show sensitivity to the values of precipitation occurring three months earlier. Meanwhile, the impacts of temperature and radiation anomalies are more immediate and dissipate shortly, pointing to a higher resilience of vegetation to these anomalies. Despite being infrequent by definition, hydro-climatic extremes are responsible for up to 10% of the vegetation variability during the 1981-2010 period in certain areas, particularly in water-limited ecosystems. Our approach is a first step towards a quantitative comparison of the resistance and resilience signature of different ecosystems, and can be used to benchmark Earth system models in their representations of past vegetation sensitivity to changes in climate.

Heating up the Galaxy with hidden photons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dubovsky, Sergei; Hernández-Chifflet, Guzmán, E-mail: dubovsky@nyu.edu, E-mail: ghc236@nyu.edu

2015-12-01

We elaborate on the dynamics of ionized interstellar medium in the presence of hidden photon dark matter. Our main focus is the ultra-light regime, where the hidden photon mass is smaller than the plasma frequency in the Milky Way. We point out that as a result of the Galactic plasma shielding direct detection of ultra-light photons in this mass range is especially challenging. However, we demonstrate that ultra-light hidden photon dark matter provides a powerful heating source for the ionized interstellar medium. This results in a strong bound on the kinetic mixing between hidden and regular photons all the waymore » down to the hidden photon masses of order 10{sup −20} eV.« less

Heating up the Galaxy with hidden photons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dubovsky, Sergei; Hernández-Chifflet, Guzmán; Instituto de Física, Facultad de Ingeniería, Universidad de la República,Montevideo, 11300

2015-12-29

We elaborate on the dynamics of ionized interstellar medium in the presence of hidden photon dark matter. Our main focus is the ultra-light regime, where the hidden photon mass is smaller than the plasma frequency in the Milky Way. We point out that as a result of the Galactic plasma shielding direct detection of ultra-light photons in this mass range is especially challenging. However, we demonstrate that ultra-light hidden photon dark matter provides a powerful heating source for the ionized interstellar medium. This results in a strong bound on the kinetic mixing between hidden and regular photons all the waymore » down to the hidden photon masses of order 10{sup −20} eV.« less

"It's Not Always What It Seems": Exploring the Hidden Curriculum within a Doctoral Program

ERIC Educational Resources Information Center

Foot, Rachel Elizabeth

2017-01-01

The purpose of this qualitative, naturalistic study was to explore the ways in which hidden curriculum might influence doctoral student success. Two questions guided the study: (a) How do doctoral students experience the hidden curriculum? (b) What forms of hidden curricula can be identified in a PhD program? Data were collected from twelve…

The hidden and informal curriculum across the continuum of training: A cross-sectional qualitative study.

PubMed

Doja, Asif; Bould, M Dylan; Clarkin, Chantalle; Eady, Kaylee; Sutherland, Stephanie; Writer, Hilary

2016-04-01

The hidden and informal curricula refer to learning in response to unarticulated processes and constraints, falling outside the formal medical curriculum. The hidden curriculum has been identified as requiring attention across all levels of learning. We sought to assess the knowledge and perceptions of the hidden and informal curricula across the continuum of learning at a single institution. Focus groups were held with undergraduate and postgraduate learners and faculty to explore knowledge and perceptions relating to the hidden and informal curricula. Thematic analysis was conducted both inductively by research team members and deductively using questions structured by the existing literature. Participants highlighted several themes related to the presence of the hidden and informal curricula in medical training and practice, including: the privileging of some specialties over others; the reinforcement of hierarchies within medicine; and a culture of tolerance towards unprofessional behaviors. Participants acknowledged the importance of role modeling in the development of professional identities and discussed the deterioration in idealism that occurs. Common issues pertaining to the hidden curriculum exist across all levels of learners, including faculty. Increased awareness of these issues could allow for the further development of methods to address learning within the hidden curriculum.

The hidden and informal curriculum across the continuum of training: A cross-sectional qualitative study.

PubMed

Doja, Asif; Bould, M Dylan; Clarkin, Chantalle; Eady, Kaylee; Sutherland, Stephanie; Writer, Hilary

2016-01-01

The hidden and informal curricula refer to learning in response to unarticulated processes and constraints, falling outside the formal medical curriculum. The hidden curriculum has been identified as requiring attention across all levels of learning. We sought to assess the knowledge and perceptions of the hidden and informal curricula across the continuum of learning at a single institution. Focus groups were held with undergraduate and postgraduate learners and faculty to explore knowledge and perceptions relating to the hidden and informal curricula. Thematic analysis was conducted both inductively by research team members and deductively using questions structured by the existing literature. Participants highlighted several themes related to the presence of the hidden and informal curricula in medical training and practice, including: the privileging of some specialties over others; the reinforcement of hierarchies within medicine; and a culture of tolerance towards unprofessional behaviors. Participants acknowledged the importance of role modeling in the development of professional identities and discussed the deterioration in idealism that occurs. Common issues pertaining to the hidden curriculum exist across all levels of learners, including faculty. Increased awareness of these issues could allow for the further development of methods to address learning within the hidden curriculum.

Hidden Farmworker Labor Camps in North Carolina: An Indicator of Structural Vulnerability

PubMed Central

Summers, Phillip; Quandt, Sara A.; Talton, Jennifer W.; Galván, Leonardo

2015-01-01

Objectives. We used geographic information systems (GIS) to delineate whether farmworker labor camps were hidden and to determine whether hidden camps differed from visible camps in terms of physical and resident characteristics. Methods. We collected data using observation, interview, and public domain GIS data for 180 farmworker labor camps in east central North Carolina. A hidden camp was defined as one that was at least 0.15 miles from an all-weather road or located behind natural or manufactured objects. Hidden camps were compared with visible camps in terms of physical and resident characteristics. Results. More than one third (37.8%) of the farmworker labor camps were hidden. Hidden camps were significantly larger (42.7% vs 17.0% with 21 or more residents; P ≤ .001; and 29.4% vs 13.5% with 3 or more dwellings; P = .002) and were more likely to include barracks (50% vs 19.6%; P ≤ .001) than were visible camps. Conclusions. Poor housing conditions in farmworker labor camps often go unnoticed because they are hidden in the rural landscape, increasing farmworker vulnerability. Policies that promote greater community engagement with farmworker labor camp residents to reduce structural vulnerability should be considered. PMID:26469658

Zipf exponent of trajectory distribution in the hidden Markov model

NASA Astrophysics Data System (ADS)

Bochkarev, V. V.; Lerner, E. Yu

2014-03-01

This paper is the first step of generalization of the previously obtained full classification of the asymptotic behavior of the probability for Markov chain trajectories for the case of hidden Markov models. The main goal is to study the power (Zipf) and nonpower asymptotics of the frequency list of trajectories of hidden Markov frequencys and to obtain explicit formulae for the exponent of the power asymptotics. We consider several simple classes of hidden Markov models. We prove that the asymptotics for a hidden Markov model and for the corresponding Markov chain can be essentially different.

A composite model for the 750 GeV diphoton excess

DOE PAGES

Harigaya, Keisuke; Nomura, Yasunori

2016-03-14

We study a simple model in which the recently reported 750 GeV diphoton excess arises from a composite pseudo Nambu-Goldstone boson — hidden pion — produced by gluon fusion and decaying into two photons. The model only introduces an extra hidden gauge group at the TeV scale with a vectorlike quark in the bifundamental representation of the hidden and standard model gauge groups. We calculate the masses of all the hidden pions and analyze their experimental signatures and constraints. We find that two colored hidden pions must be near the current experimental limits, and hence are probed in the nearmore » future. We study physics of would-be stable particles — the composite states that do not decay purely by the hidden and standard model gauge dynamics — in detail, including constraints from cosmology. We discuss possible theoretical structures above the TeV scale, e.g. conformal dynamics and supersymmetry, and their phenomenological implications. We also discuss an extension of the minimal model in which there is an extra hidden quark that is singlet under the standard model and has a mass smaller than the hidden dynamical scale. This provides two standard model singlet hidden pions that can both be viewed as diphoton/diboson resonances produced by gluon fusion. We discuss several scenarios in which these (and other) resonances can be used to explain various excesses seen in the LHC data.« less

Radio for hidden-photon dark matter detection

DOE PAGES

Chaudhuri, Saptarshi; Graham, Peter W.; Irwin, Kent; ...

2015-10-08

We propose a resonant electromagnetic detector to search for hidden-photon dark matter over an extensive range of masses. Hidden-photon dark matter can be described as a weakly coupled “hidden electric field,” oscillating at a frequency fixed by the mass, and able to penetrate any shielding. At low frequencies (compared to the inverse size of the shielding), we find that the observable effect of the hidden photon inside any shielding is a real, oscillating magnetic field. We outline experimental setups designed to search for hidden-photon dark matter, using a tunable, resonant LC circuit designed to couple to this magnetic field. Ourmore » “straw man” setups take into consideration resonator design, readout architecture and noise estimates. At high frequencies, there is an upper limit to the useful size of a single resonator set by 1/ν. However, many resonators may be multiplexed within a hidden-photon coherence length to increase the sensitivity in this regime. Hidden-photon dark matter has an enormous range of possible frequencies, but current experiments search only over a few narrow pieces of that range. As a result, we find the potential sensitivity of our proposal is many orders of magnitude beyond current limits over an extensive range of frequencies, from 100 Hz up to 700 GHz and potentially higher.« less

PCSYS: The optimal design integration system picture drawing system with hidden line algorithm capability for aerospace vehicle configurations

NASA Technical Reports Server (NTRS)

Hague, D. S.; Vanderburg, J. D.

1977-01-01

A vehicle geometric definition based upon quadrilateral surface elements to produce realistic pictures of an aerospace vehicle. The PCSYS programs can be used to visually check geometric data input, monitor geometric perturbations, and to visualize the complex spatial inter-relationships between the internal and external vehicle components. PCSYS has two major component programs. The between program, IMAGE, draws a complex aerospace vehicle pictorial representation based on either an approximate but rapid hidden line algorithm or without any hidden line algorithm. The second program, HIDDEN, draws a vehicle representation using an accurate but time consuming hidden line algorithm.

Diet, bite force and skull morphology in the generalist rodent morphotype.

PubMed

Maestri, R; Patterson, B D; Fornel, R; Monteiro, L R; de Freitas, T R O

2016-11-01

For many vertebrate species, bite force plays an important functional role. Ecological characteristics of a species' niche, such as diet, are often associated with bite force. Previous evidence suggests a biomechanical trade-off between rodents specialized for gnawing, which feed mainly on seeds, and those specialized for chewing, which feed mainly on green vegetation. We tested the hypothesis that gnawers are stronger biters than chewers. We estimated bite force and measured skull and mandible shape and size in 63 genera of a major rodent radiation (the myomorph sigmodontines). Analysis of the influence of diet on bite force and morphology was made in a comparative framework. We then used phylogenetic path analysis to uncover the most probable causal relationships linking diet and bite force. Both granivores (gnawers) and herbivores (chewers) have a similar high bite force, leading us to reject the initial hypothesis. Path analysis reveals that bite force is more likely influenced by diet than the reverse causality. The absence of a trade-off between herbivores and granivores may be associated with the generalist nature of the myomorph condition seen in sigmodontine rodents. Both gnawing and chewing sigmodontines exhibit similar, intermediate phenotypes, at least compared to extreme gnawers (squirrels) and chewers (chinchillas). Only insectivorous rodents appear to be moving towards a different direction in the shape space, through some notable changes in morphology. In terms of diet, natural selection alters bite force through changes in size and shape, indicating that organisms adjust their bite force in tandem with changes in food items. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Staying green postharvest: how three mutations in the Arabidopsis chlorophyll b reductase gene NYC1 delay degreening by distinct mechanisms.

PubMed

Jibran, Rubina; Sullivan, Kerry L; Crowhurst, Ross; Erridge, Zoe A; Chagné, David; McLachlan, Andrew R G; Brummell, David A; Dijkwel, Paul P; Hunter, Donald A

2015-11-01

Stresses such as energy deprivation, wounding and water-supply disruption often contribute to rapid deterioration of harvested tissues. To uncover the genetic regulation behind such stresses, a simple assessment system was used to detect senescence mutants in conjunction with two rapid mapping techniques to identify the causal mutations. To demonstrate the power of this approach, immature inflorescences of Arabidopsis plants that contained ethyl methanesulfonate-induced lesions were detached and screened for altered timing of dark-induced senescence. Numerous mutant lines displaying accelerated or delayed timing of senescence relative to wild type were discovered. The underlying mutations in three of these were identified using High Resolution Melting analysis to map to a chromosomal arm followed by a whole-genome sequencing-based mapping method, termed 'Needle in the K-Stack', to identify the causal lesions. All three mutations were single base pair changes and occurred in the same gene, NON-YELLOW COLORING1 (NYC1), a chlorophyll b reductase of the short-chain dehydrogenase/reductase (SDR) superfamily. This was consistent with the mutants preferentially retaining chlorophyll b, although substantial amounts of chlorophyll b were still lost. The single base pair mutations disrupted NYC1 function by three distinct mechanisms, one by producing a termination codon, the second by interfering with correct intron splicing and the third by replacing a highly conserved proline with a non-equivalent serine residue. This non-synonymous amino acid change, which occurred in the NADPH binding domain of NYC1, is the first example of such a mutation in an SDR protein inhibiting a physiological response in plants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Information transfer across the scales of climate data variability

NASA Astrophysics Data System (ADS)

Palus, Milan; Jajcay, Nikola; Hartman, David; Hlinka, Jaroslav

2015-04-01

Multitude of scales characteristic of the climate system variability requires innovative approaches in analysis of instrumental time series. We present a methodology which starts with a wavelet decomposition of a multi-scale signal into quasi-oscillatory modes of a limited band-with, described using their instantaneous phases and amplitudes. Then their statistical associations are tested in order to search for interactions across time scales. In particular, an information-theoretic formulation of the generalized, nonlinear Granger causality is applied together with surrogate data testing methods [1]. The method [2] uncovers causal influence (in the Granger sense) and information transfer from large-scale modes of climate variability with characteristic time scales from years to almost a decade to regional temperature variability on short time scales. In analyses of daily mean surface air temperature from various European locations an information transfer from larger to smaller scales has been observed as the influence of the phase of slow oscillatory phenomena with periods around 7-8 years on amplitudes of the variability characterized by smaller temporal scales from a few months to annual and quasi-biennial scales [3]. In sea surface temperature data from the tropical Pacific area an influence of quasi-oscillatory phenomena with periods around 4-6 years on the variability on and near the annual scale has been observed. This study is supported by the Ministry of Education, Youth and Sports of the Czech Republic within the Program KONTAKT II, Project No. LH14001. [1] M. Palus, M. Vejmelka, Phys. Rev. E 75, 056211 (2007) [2] M. Palus, Entropy 16(10), 5263-5289 (2014) [3] M. Palus, Phys. Rev. Lett. 112, 078702 (2014)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farina, Marco; Pappadopulo, Duccio; Ruderman, Joshua T.

A hidden sector with a mass gap undergoes an epoch of cannibalism if number changing interactions are active when the temperature drops below the mass of the lightest hidden particle. During cannibalism, the hidden sector temperature decreases only logarithmically with the scale factor. We consider the possibility that dark matter resides in a hidden sector that underwent cannibalism, and has relic density set by the freeze-out of two-to-two annihilations. We identify three novel phases, depending on the behavior of the hidden sector when dark matter freezes out. During the cannibal phase, dark matter annihilations decouple while the hidden sector ismore » cannibalizing. During the chemical phase, only two-to-two interactions are active and the total number of hidden particles is conserved. During the one way phase, the dark matter annihilation products decay out of equilibrium, suppressing the production of dark matter from inverse annihilations. We map out the distinct phenomenology of each phase, which includes a boosted dark matter annihilation rate, new relativistic degrees of freedom, warm dark matter, and observable distortions to the spectrum of the cosmic microwave background.« less

Phases of cannibal dark matter

NASA Astrophysics Data System (ADS)

Farina, Marco; Pappadopulo, Duccio; Ruderman, Joshua T.; Trevisan, Gabriele

2016-12-01

A hidden sector with a mass gap undergoes an epoch of cannibalism if number changing interactions are active when the temperature drops below the mass of the lightest hidden particle. During cannibalism, the hidden sector temperature decreases only logarithmically with the scale factor. We consider the possibility that dark matter resides in a hidden sector that underwent cannibalism, and has relic density set by the freeze-out of two-to-two annihilations. We identify three novel phases, depending on the behavior of the hidden sector when dark matter freezes out. During the cannibal phase, dark matter annihilations decouple while the hidden sector is cannibalizing. During the chemical phase, only two-to-two interactions are active and the total number of hidden particles is conserved. During the one way phase, the dark matter annihilation products decay out of equilibrium, suppressing the production of dark matter from inverse annihilations. We map out the distinct phenomenology of each phase, which includes a boosted dark matter annihilation rate, new relativistic degrees of freedom, warm dark matter, and observable distortions to the spectrum of the cosmic microwave background.

Phases of cannibal dark matter

DOE PAGES

Farina, Marco; Pappadopulo, Duccio; Ruderman, Joshua T.; ...

2016-12-13

A hidden sector with a mass gap undergoes an epoch of cannibalism if number changing interactions are active when the temperature drops below the mass of the lightest hidden particle. During cannibalism, the hidden sector temperature decreases only logarithmically with the scale factor. We consider the possibility that dark matter resides in a hidden sector that underwent cannibalism, and has relic density set by the freeze-out of two-to-two annihilations. We identify three novel phases, depending on the behavior of the hidden sector when dark matter freezes out. During the cannibal phase, dark matter annihilations decouple while the hidden sector ismore » cannibalizing. During the chemical phase, only two-to-two interactions are active and the total number of hidden particles is conserved. During the one way phase, the dark matter annihilation products decay out of equilibrium, suppressing the production of dark matter from inverse annihilations. We map out the distinct phenomenology of each phase, which includes a boosted dark matter annihilation rate, new relativistic degrees of freedom, warm dark matter, and observable distortions to the spectrum of the cosmic microwave background.« less

Generalization and capacity of extensively large two-layered perceptrons.

PubMed

Rosen-Zvi, Michal; Engel, Andreas; Kanter, Ido

2002-09-01

The generalization ability and storage capacity of a treelike two-layered neural network with a number of hidden units scaling as the input dimension is examined. The mapping from the input to the hidden layer is via Boolean functions; the mapping from the hidden layer to the output is done by a perceptron. The analysis is within the replica framework where an order parameter characterizing the overlap between two networks in the combined space of Boolean functions and hidden-to-output couplings is introduced. The maximal capacity of such networks is found to scale linearly with the logarithm of the number of Boolean functions per hidden unit. The generalization process exhibits a first-order phase transition from poor to perfect learning for the case of discrete hidden-to-output couplings. The critical number of examples per input dimension, alpha(c), at which the transition occurs, again scales linearly with the logarithm of the number of Boolean functions. In the case of continuous hidden-to-output couplings, the generalization error decreases according to the same power law as for the perceptron, with the prefactor being different.

Out of Reach, Out of Mind? Infants' Comprehension of References to Hidden Inaccessible Objects.

PubMed

Osina, Maria A; Saylor, Megan M; Ganea, Patricia A

2017-09-01

This study investigated the nature of infants' difficulty understanding references to hidden inaccessible objects. Twelve-month-old infants (N = 32) responded to the mention of objects by looking at, pointing at, or approaching them when the referents were visible or accessible, but not when they were hidden and inaccessible (Experiment I). Twelve-month-olds (N = 16) responded robustly when a container with the hidden referent was moved from a previously inaccessible position to an accessible position before the request, but failed to respond when the reverse occurred (Experiment II). This suggests that infants might be able to track the hidden object's dislocations and update its accessibility as it changes. Knowing the hidden object is currently inaccessible inhibits their responding. Older, 16-month-old (N = 17) infants' performance was not affected by object accessibility. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

Robot-assisted surgery: an emerging platform for human neuroscience research

PubMed Central

Jarc, Anthony M.; Nisky, Ilana

2015-01-01

Classic studies in human sensorimotor control use simplified tasks to uncover fundamental control strategies employed by the nervous system. Such simple tasks are critical for isolating specific features of motor, sensory, or cognitive processes, and for inferring causality between these features and observed behavioral changes. However, it remains unclear how these theories translate to complex sensorimotor tasks or to natural behaviors. Part of the difficulty in performing such experiments has been the lack of appropriate tools for measuring complex motor skills in real-world contexts. Robot-assisted surgery (RAS) provides an opportunity to overcome these challenges by enabling unobtrusive measurements of user behavior. In addition, a continuum of tasks with varying complexity—from simple tasks such as those in classic studies to highly complex tasks such as a surgical procedure—can be studied using RAS platforms. Finally, RAS includes a diverse participant population of inexperienced users all the way to expert surgeons. In this perspective, we illustrate how the characteristics of RAS systems make them compelling platforms to extend many theories in human neuroscience, as well as, to develop new theories altogether. PMID:26089785

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice

PubMed Central

Wang, I-Ting Judy; Allen, Megan; Goffin, Darren; Zhu, Xinjian; Fairless, Andrew H.; Brodkin, Edward S.; Siegel, Steve J.; Marsh, Eric D.; Blendy, Julie A.; Zhou, Zhaolan

2012-01-01

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKT-mammalian target of rapamycin (mTOR) cascade, upon Cdkl5 loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for Cdkl5 loss-of-function in neurodevelopmental disorders. PMID:23236174

An Integrated Systems Biology Approach Identifies TRIM25 as a Key Determinant of Breast Cancer Metastasis.

PubMed

Walsh, Logan A; Alvarez, Mariano J; Sabio, Erich Y; Reyngold, Marsha; Makarov, Vladimir; Mukherjee, Suranjit; Lee, Ken-Wing; Desrichard, Alexis; Turcan, Şevin; Dalin, Martin G; Rajasekhar, Vinagolu K; Chen, Shuibing; Vahdat, Linda T; Califano, Andrea; Chan, Timothy A

2017-08-15

At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, the complex regulatory networks presiding over the initiation and maintenance of metastatic tumors are still poorly understood. There is untapped value in identifying therapeutic targets that broadly govern coordinated transcriptional modules dictating metastatic progression. Here, we reverse engineered and interrogated a breast cancer-specific transcriptional interaction network (interactome) to define transcriptional control structures causally responsible for regulating genetic programs underlying breast cancer metastasis in individual patients. Our analyses confirmed established pro-metastatic transcription factors, and they uncovered TRIM25 as a key regulator of metastasis-related transcriptional programs. Further, in vivo analyses established TRIM25 as a potent regulator of metastatic disease and poor survival outcome. Our findings suggest that identifying and targeting keystone proteins, like TRIM25, can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing an innovative cancer intervention strategy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Depth-specific optogenetic control in vivo with a scalable, high-density μLED neural probe

NASA Astrophysics Data System (ADS)

Scharf, Robert; Tsunematsu, Tomomi; McAlinden, Niall; Dawson, Martin D.; Sakata, Shuzo; Mathieson, Keith

2016-06-01

Controlling neural circuits is a powerful approach to uncover a causal link between neural activity and behaviour. Optogenetics has been widely adopted by the neuroscience community as it offers cell-type-specific perturbation with millisecond precision. However, these studies require light delivery in complex patterns with cellular-scale resolution, while covering a large volume of tissue at depth in vivo. Here we describe a novel high-density silicon-based microscale light-emitting diode (μLED) array, consisting of up to ninety-six 25 μm-diameter μLEDs emitting at a wavelength of 450 nm with a peak irradiance of 400 mW/mm2. A width of 100 μm, tapering to a 1 μm point, and a 40 μm thickness help minimise tissue damage during insertion. Thermal properties permit a set of optogenetic operating regimes, with ~0.5 °C average temperature increase. We demonstrate depth-dependent activation of mouse neocortical neurons in vivo, offering an inexpensive novel tool for the precise manipulation of neural activity.

A de novo FOXP1 variant in a patient with autism, intellectual disability and severe speech and language impairment.

PubMed

Lozano, Reymundo; Vino, Arianna; Lozano, Cristina; Fisher, Simon E; Deriziotis, Pelagia

2015-12-01

FOXP1 (forkhead box protein P1) is a transcription factor involved in the development of several tissues, including the brain. An emerging phenotype of patients with protein-disrupting FOXP1 variants includes global developmental delay, intellectual disability and mild to severe speech/language deficits. We report on a female child with a history of severe hypotonia, autism spectrum disorder and mild intellectual disability with severe speech/language impairment. Clinical exome sequencing identified a heterozygous de novo FOXP1 variant c.1267_1268delGT (p.V423Hfs*37). Functional analyses using cellular models show that the variant disrupts multiple aspects of FOXP1 activity, including subcellular localization and transcriptional repression properties. Our findings highlight the importance of performing functional characterization to help uncover the biological significance of variants identified by genomics approaches, thereby providing insight into pathways underlying complex neurodevelopmental disorders. Moreover, our data support the hypothesis that de novo variants represent significant causal factors in severe sporadic disorders and extend the phenotype seen in individuals with FOXP1 haploinsufficiency.

Grapevine Pathogenic Microorganisms: Understanding Infection Strategies and Host Response Scenarios

PubMed Central

Armijo, Grace; Schlechter, Rudolf; Agurto, Mario; Muñoz, Daniela; Nuñez, Constanza; Arce-Johnson, Patricio

2016-01-01

Grapevine (Vitis vinifera L.) is one of the most important fruit crop worldwide. Commercial cultivars are greatly affected by a large number of pathogenic microorganisms that cause diseases during pre- and/or post-harvest periods, affecting production, processing and export, along with fruit quality. Among the potential threats, we can find bacteria, fungi, oomycete, or viruses with different life cycles, infection mechanisms and evasion strategies. While plant–pathogen interactions are cycles of resistance and susceptibility, resistance traits from natural resources are selected and may be used for breeding purposes and for a sustainable agriculture. In this context, here we summarize some of the most important diseases affecting V. vinifera together with their causal agents. The aim of this work is to bring a comprehensive review of the infection strategies deployed by significant types of pathogens while understanding the host response in both resistance and susceptibility scenarios. New approaches being used to uncover grapevine status during biotic stresses and scientific-based procedures needed to control plant diseases and crop protection are also addressed. PMID:27066032

Activation of intestinal hypoxia-inducible factor 2α during obesity contributes to hepatic steatosis.

PubMed

Xie, Cen; Yagai, Tomoki; Luo, Yuhong; Liang, Xianyi; Chen, Tao; Wang, Qiong; Sun, Dongxue; Zhao, Jie; Ramakrishnan, Sadeesh K; Sun, Lulu; Jiang, Chunmei; Xue, Xiang; Tian, Yuan; Krausz, Kristopher W; Patterson, Andrew D; Shah, Yatrik M; Wu, Yue; Jiang, Changtao; Gonzalez, Frank J

2017-11-01

Nonalcoholic fatty liver disease is becoming the most common chronic liver disease in Western countries, and limited therapeutic options are available. Here we uncovered a role for intestinal hypoxia-inducible factor (HIF) in hepatic steatosis. Human-intestine biopsies from individuals with or without obesity revealed that intestinal HIF-2α signaling was positively correlated with body-mass index and hepatic toxicity. The causality of this correlation was verified in mice with an intestine-specific disruption of Hif2a, in which high-fat-diet-induced hepatic steatosis and obesity were substantially lower as compared to control mice. PT2385, a HIF-2α-specific inhibitor, had preventive and therapeutic effects on metabolic disorders that were dependent on intestine HIF-2α. Intestine HIF-2α inhibition markedly reduced intestine and serum ceramide levels. Mechanistically, intestine HIF-2α regulates ceramide metabolism mainly from the salvage pathway, by positively regulating the expression of Neu3, the gene encoding neuraminidase 3. These results suggest that intestinal HIF-2α could be a viable target for hepatic steatosis therapy.

Screen Media Exposure and Obesity in Children and Adolescents

PubMed Central

Robinson, Thomas N.; Banda, Jorge A.; Hale, Lauren; Lu, Amy Shirong; Fleming-Milici, Frances; Calvert, Sandra L.; Wartella, Ellen

2018-01-01

Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children’s preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context. PMID:29093041

Introduction to neutron stars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lattimer, James M.

Neutron stars contain the densest form of matter in the present universe. General relativity and causality set important constraints to their compactness. In addition, analytic GR solutions are useful in understanding the relationships that exist among the maximum mass, radii, moments of inertia, and tidal Love numbers of neutron stars, all of which are accessible to observation. Some of these relations are independent of the underlying dense matter equation of state, while others are very sensitive to the equation of state. Recent observations of neutron stars from pulsar timing, quiescent X-ray emission from binaries, and Type I X-ray bursts canmore » set important constraints on the structure of neutron stars and the underlying equation of state. In addition, measurements of thermal radiation from neutron stars has uncovered the possible existence of neutron and proton superfluidity/superconductivity in the core of a neutron star, as well as offering powerful evidence that typical neutron stars have significant crusts. These observations impose constraints on the existence of strange quark matter stars, and limit the possibility that abundant deconfined quark matter or hyperons exist in the cores of neutron stars.« less

NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.

PubMed

Singh-Taylor, A; Molet, J; Jiang, S; Korosi, A; Bolton, J L; Noam, Y; Simeone, K; Cope, J; Chen, Y; Mortazavi, A; Baram, T Z

2018-03-01

Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.

PubMed

Teissier, Anne; Chemiakine, Alexei; Inbar, Benjamin; Bagchi, Sneha; Ray, Russell S; Palmiter, Richard D; Dymecki, Susan M; Moore, Holly; Ansorge, Mark S

2015-12-01

Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Introduction to neutron stars

NASA Astrophysics Data System (ADS)

Lattimer, James M.

2015-02-01

Neutron stars contain the densest form of matter in the present universe. General relativity and causality set important constraints to their compactness. In addition, analytic GR solutions are useful in understanding the relationships that exist among the maximum mass, radii, moments of inertia, and tidal Love numbers of neutron stars, all of which are accessible to observation. Some of these relations are independent of the underlying dense matter equation of state, while others are very sensitive to the equation of state. Recent observations of neutron stars from pulsar timing, quiescent X-ray emission from binaries, and Type I X-ray bursts can set important constraints on the structure of neutron stars and the underlying equation of state. In addition, measurements of thermal radiation from neutron stars has uncovered the possible existence of neutron and proton superfluidity/superconductivity in the core of a neutron star, as well as offering powerful evidence that typical neutron stars have significant crusts. These observations impose constraints on the existence of strange quark matter stars, and limit the possibility that abundant deconfined quark matter or hyperons exist in the cores of neutron stars.

Clinical Management of Implant Prostheses in Patients with Bruxism

PubMed Central

Komiyama, Osamu; Lobbezoo, Frank; De Laat, Antoon; Iida, Takashi; Kitagawa, Tsuyoshi; Murakami, Hiroshi; Kato, Takao; Kawara, Misao

2012-01-01

There is general agreement that excessive stress to the bone-implant interface may result in implant overload and failure. Early failure of the implant due to excessive loading occurs shortly after uncovering the implant. Excess load on a final restoration after successful implant integration can result in physical failure of the implant structure. Many clinicians believe that overload of dental implants is a risk factor for vertical peri-implant bone loss and/or may be detrimental for the suprastructure in implant prostheses. It has been documented that occlusal parafunction, such as, bruxism (tooth grinding and clenching) affects the outcome of implant prostheses, but there is no evidence for a causal relation between the failures and overload of dental implants. In spite of this lack of evidence, often metal restorations are preferred instead of porcelain for patients in whom bruxism is presumed on the basis of tooth wear. The purpose of this paper is to discuss the importance of the occlusal scheme used in implant restorations for implant longevity and to suggest a clinical approach and occlusal materials for implant prostheses in order to prevent complications related to bruxism. PMID:22701484

Integrating Insults: Using Fault Tree Analysis to Guide Schizophrenia Research across Levels of Analysis

PubMed Central

MacDonald III, Angus W.; Zick, Jennifer L.; Chafee, Matthew V.; Netoff, Theoden I.

2016-01-01

The grand challenges of schizophrenia research are linking the causes of the disorder to its symptoms and finding ways to overcome those symptoms. We argue that the field will be unable to address these challenges within psychiatry’s standard neo-Kraepelinian (DSM) perspective. At the same time the current corrective, based in molecular genetics and cognitive neuroscience, is also likely to flounder due to its neglect for psychiatry’s syndromal structure. We suggest adopting a new approach long used in reliability engineering, which also serves as a synthesis of these approaches. This approach, known as fault tree analysis, can be combined with extant neuroscientific data collection and computational modeling efforts to uncover the causal structures underlying the cognitive and affective failures in people with schizophrenia as well as other complex psychiatric phenomena. By making explicit how causes combine from basic faults to downstream failures, this approach makes affordances for: (1) causes that are neither necessary nor sufficient in and of themselves; (2) within-diagnosis heterogeneity; and (3) between diagnosis co-morbidity. PMID:26779007

Unique among ciliopathies: primary ciliary dyskinesia, a motile cilia disorder.

PubMed

Praveen, Kavita; Davis, Erica E; Katsanis, Nicholas

2015-01-01

Primary ciliary dyskinesia (PCD) is a ciliopathy, but represents the sole entity from this class of disorders that results from the dysfunction of motile cilia. Characterized by respiratory problems appearing in childhood, infertility, and situs defects in ~50% of individuals, PCD has an estimated prevalence of approximately 1 in 10,000 live births. The diagnosis of PCD can be prolonged due to a lack of disease awareness, coupled with the fact that symptoms can be confused with other more common genetic disorders, such as cystic fibrosis, or environmental insults that result in frequent respiratory infections. A primarily autosomal recessive disorder, PCD is genetically heterogeneous with >30 causal genes identified, posing significant challenges to genetic diagnosis. Here, we provide an overview of PCD as a disorder underscored by impaired ciliary motility; we discuss the recent advances towards uncovering the genetic basis of PCD; we discuss the molecular knowledge gained from PCD gene discovery, which has improved our understanding of motile ciliary assembly; and we speculate on how accelerated diagnosis, together with detailed phenotypic data, will shape the genetic and functional architecture of this disorder.

Learning and inference in a nonequilibrium Ising model with hidden nodes.

PubMed

Dunn, Benjamin; Roudi, Yasser

2013-02-01

We study inference and reconstruction of couplings in a partially observed kinetic Ising model. With hidden spins, calculating the likelihood of a sequence of observed spin configurations requires performing a trace over the configurations of the hidden ones. This, as we show, can be represented as a path integral. Using this representation, we demonstrate that systematic approximate inference and learning rules can be derived using dynamical mean-field theory. Although naive mean-field theory leads to an unstable learning rule, taking into account Gaussian corrections allows learning the couplings involving hidden nodes. It also improves learning of the couplings between the observed nodes compared to when hidden nodes are ignored.

Mining geographic variations of Plasmodium vivax for active surveillance: a case study in China.

PubMed

Shi, Benyun; Tan, Qi; Zhou, Xiao-Nong; Liu, Jiming

2015-05-27

Geographic variations of an infectious disease characterize the spatial differentiation of disease incidences caused by various impact factors, such as environmental, demographic, and socioeconomic factors. Some factors may directly determine the force of infection of the disease (namely, explicit factors), while many other factors may indirectly affect the number of disease incidences via certain unmeasurable processes (namely, implicit factors). In this study, the impact of heterogeneous factors on geographic variations of Plasmodium vivax incidences is systematically investigate in Tengchong, Yunnan province, China. A space-time model that resembles a P. vivax transmission model and a hidden time-dependent process, is presented by taking into consideration both explicit and implicit factors. Specifically, the transmission model is built upon relevant demographic, environmental, and biophysical factors to describe the local infections of P. vivax. While the hidden time-dependent process is assessed by several socioeconomic factors to account for the imported cases of P. vivax. To quantitatively assess the impact of heterogeneous factors on geographic variations of P. vivax infections, a Markov chain Monte Carlo (MCMC) simulation method is developed to estimate the model parameters by fitting the space-time model to the reported spatial-temporal disease incidences. Since there is no ground-truth information available, the performance of the MCMC method is first evaluated against a synthetic dataset. The results show that the model parameters can be well estimated using the proposed MCMC method. Then, the proposed model is applied to investigate the geographic variations of P. vivax incidences among all 18 towns in Tengchong, Yunnan province, China. Based on the geographic variations, the 18 towns can be further classify into five groups with similar socioeconomic causality for P. vivax incidences. Although this study focuses mainly on the transmission of P. vivax, the proposed space-time model is general and can readily be extended to investigate geographic variations of other diseases. Practically, such a computational model will offer new insights into active surveillance and strategic planning for disease surveillance and control.

Enhancing Cognition with Video Games: A Multiple Game Training Study

PubMed Central

Oei, Adam C.; Patterson, Michael D.

2013-01-01

Background Previous evidence points to a causal link between playing action video games and enhanced cognition and perception. However, benefits of playing other video games are under-investigated. We examined whether playing non-action games also improves cognition. Hence, we compared transfer effects of an action and other non-action types that required different cognitive demands. Methodology/Principal Findings We instructed 5 groups of non-gamer participants to play one game each on a mobile device (iPhone/iPod Touch) for one hour a day/five days a week over four weeks (20 hours). Games included action, spatial memory, match-3, hidden- object, and an agent-based life simulation. Participants performed four behavioral tasks before and after video game training to assess for transfer effects. Tasks included an attentional blink task, a spatial memory and visual search dual task, a visual filter memory task to assess for multiple object tracking and cognitive control, as well as a complex verbal span task. Action game playing eliminated attentional blink and improved cognitive control and multiple-object tracking. Match-3, spatial memory and hidden object games improved visual search performance while the latter two also improved spatial working memory. Complex verbal span improved after match-3 and action game training. Conclusion/Significance Cognitive improvements were not limited to action game training alone and different games enhanced different aspects of cognition. We conclude that training specific cognitive abilities frequently in a video game improves performance in tasks that share common underlying demands. Overall, these results suggest that many video game-related cognitive improvements may not be due to training of general broad cognitive systems such as executive attentional control, but instead due to frequent utilization of specific cognitive processes during game play. Thus, many video game training related improvements to cognition may be attributed to near-transfer effects. PMID:23516504

Life imitating art: depictions of the hidden curriculum in medical television programs.

PubMed

Stanek, Agatha; Clarkin, Chantalle; Bould, M Dylan; Writer, Hilary; Doja, Asif

2015-09-26

The hidden curriculum represents influences occurring within the culture of medicine that indirectly alter medical professionals' interactions, beliefs and clinical practices throughout their training. One approach to increase medical student awareness of the hidden curriculum is to provide them with readily available examples of how it is enacted in medicine; as such the purpose of this study was to examine depictions of the hidden curriculum in popular medical television programs. One full season of ER, Grey's Anatomy and Scrubs were selected for review. A summative content analysis was performed to ascertain the presence of depictions of the hidden curriculum, as well as to record the type, frequency and quality of examples. A second reviewer also viewed a random selection of episodes from each series to establish coding reliability. The most prevalent themes across all television programs were: the hierarchical nature of medicine; challenges during transitional stages in medicine; the importance of role modeling; patient dehumanization; faking or overstating one's capabilities; unprofessionalism; the loss of idealism; and difficulties with work-life balance. The hidden curriculum is frequently depicted in popular medical television shows. These examples of the hidden curriculum could serve as a valuable teaching resource in undergraduate medical programs.

Effect of Ixekizumab Treatment on Work Productivity for Patients With Moderate-to-Severe Plaque Psoriasis: Analysis of Results From 3 Randomized Phase 3 Clinical Trials.

PubMed

Armstrong, April W; Lynde, Charles W; McBride, Sandy R; Ståhle, Mona; Edson-Heredia, Emily; Zhu, Baojin; Amato, David; Nikaï, Enkeleida; Yang, Fan Emily; Gordon, Kenneth B

2016-06-01

Therapies that reduce psoriasis symptoms may improve work productivity. To assess the effect of ixekizumab therapy on work productivity, measured by the Work Productivity and Activity Impairment-Psoriasis (WPAI-PSO). Three multicenter, randomized double-blind phase 3 trials conducted during the following periods: December 2011 through August 2014 (UNCOVER-1), May 2012 through April 2015 (UNCOVER-2), and August 2012 through July 2014 (UNCOVER-3). Adult outpatients with moderate-to-severe chronic plaque psoriasis were included. In UNCOVER-1, patients were randomized 1:1:1 to subcutaneous placebo or 80 mg ixekizumab every 2 weeks (Q2W) or every 4 weeks (Q4W) for 12 weeks; UNCOVER-2 and UNCOVER-3 also had an etanercept arm (50 mg twice weekly). Maintenance of initial ixekizumab response was evaluated in UNCOVER-1 and UNCOVER-2 during a randomized withdrawal period following week 12 through week 60. The WPAI-PSO questionnaire was administered at baseline and week 12 for all patients and at weeks 24, 36, 52, and 60 for patients in UNCOVER-1 and UNCOVER-2. Change in work productivity from baseline as measured by WPAI-PSO scores. Across trials, 5101 patients consented; 3866 were randomized (mean [SD] age, UNCOVER-1, 45.7 [12.9] y, 68.1% male; UNCOVER-2: 45.0 [13.0] y, 67.1% male; UNCOVER-3: 45.8 [13.1] y, 68.2% male). At week 12 in UNCOVER-1, the ixekizumab Q4W and ixekizumab Q2W groups showed significantly greater improvements in WPAI-PSO scores (least squares mean change from baseline [SE]) relative to placebo: absenteeism (-3.5 [0.87], P < .001; -2.6 [0.84], P = .003, respectively, vs 0.2 [0.88]), presenteeism (-18.8 [1.28], P < .001; -18.3 [1.24], P < .001, vs 0.5 [1.30]), work productivity loss (-20.6 [1.38], P < .001; -19.8 [1.33], P < .001, vs -0.8 [1.40]), and activity impairment (-24.5 [1.18], P < .001; -25.2 [1.15], P < .001, vs 0.8 [1.18]). Similar results were obtained for UNCOVER-2 and UNCOVER-3, with the exception of absenteeism with ixekizumab Q4W in UNCOVER-2. Additionally, ixekizumab-treated patients showed significantly greater improvements in WPAI-PSO scores vs etanercept-treated patients: UNCOVER-2: presenteeism, work productivity loss, activity impairment (P < .001 both doses), UNCOVER-3: activity impairment (ie, regular activities outside of work) (ixekizumab Q2W; P = .009). Improvements in WPAI-PSO scores at week 12 were sustained to at least week 60. Ixekizumab-treated patients reported short- and long-term improvements in work productivity, which could lead to reduced productivity-related cost burden in patients with psoriasis. clinicaltrials.gov Identifiers: NCT01474512, NCT01597245, NCT01646177.

The Politics of the Hidden Curriculum

ERIC Educational Resources Information Center

Giroux, Henry A.

1977-01-01

Schools teach much more than the traditional curriculum. They also teach a "hidden curriculum"--those unstated norms, values, and beliefs promoting hierarchic and authoritarian social relations that are transmitted to students through the underlying educational structure. Discusses the effects of the "hidden curriculum" on the…

Birefringence and hidden photons

NASA Astrophysics Data System (ADS)

Arza, Ariel; Gamboa, J.

2018-05-01

We study a model where photons interact with hidden photons and millicharged particles through a kinetic mixing term. Particularly, we focus on vacuum birefringence effects and we find a bound for the millicharged parameter assuming that hidden photons are a piece of the local dark matter density.

Extreme negotiations.

PubMed

Weiss, Jeff; Donigian, Aram; Hughes, Jonathan

2010-11-01

CEOs and other senior executives must make countless complex, high-stakes deals across functional areas and divisions, with alliance partners and critical suppliers, and with customers and regulators. The pressure of such negotiations may make them feel a lot like U.S. military officers in an Afghan village, fending off enemy fire while trying to win trust and get intelligence from the local populace. Both civilian and military leaders face what the authors call "dangerous negotiations," in which the traps are many and good advice is scarce. Although the sources of danger are quite different for executives and officers, they resort to the same kinds of behaviors. Both feel pressure to make quick progress, project strength and control (particularly when they have neither), rely on force rather than collaboration, trade resources for cooperation rather than build trust, and make unwanted compromises to minimize potential damage. The authors outline five core strategies that "in extremis" military negotiators use to resolve conflicts and influence others: maintaining a big-picture perspective; uncovering hidden agendas to improve collaboration; using facts and fairness to get buy-in; building trust; and focusing on process as well as outcomes. These strategies provide an effective framework that business executives can use to prepare for a negotiation and guide their moves at the bargaining table.

A Network Based Method for Analysis of lncRNA-Disease Associations and Prediction of lncRNAs Implicated in Diseases

PubMed Central

Yang, Xiaofei; Gao, Lin; Guo, Xingli; Shi, Xinghua; Wu, Hao; Song, Fei; Wang, Bingbo

2014-01-01

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer's disease, pancreatic cancer, and gastric cancer were verified by other independent studies. PMID:24498199

The potential of text mining in data integration and network biology for plant research: a case study on Arabidopsis.

PubMed

Van Landeghem, Sofie; De Bodt, Stefanie; Drebert, Zuzanna J; Inzé, Dirk; Van de Peer, Yves

2013-03-01

Despite the availability of various data repositories for plant research, a wealth of information currently remains hidden within the biomolecular literature. Text mining provides the necessary means to retrieve these data through automated processing of texts. However, only recently has advanced text mining methodology been implemented with sufficient computational power to process texts at a large scale. In this study, we assess the potential of large-scale text mining for plant biology research in general and for network biology in particular using a state-of-the-art text mining system applied to all PubMed abstracts and PubMed Central full texts. We present extensive evaluation of the textual data for Arabidopsis thaliana, assessing the overall accuracy of this new resource for usage in plant network analyses. Furthermore, we combine text mining information with both protein-protein and regulatory interactions from experimental databases. Clusters of tightly connected genes are delineated from the resulting network, illustrating how such an integrative approach is essential to grasp the current knowledge available for Arabidopsis and to uncover gene information through guilt by association. All large-scale data sets, as well as the manually curated textual data, are made publicly available, hereby stimulating the application of text mining data in future plant biology studies.

First-principles approach to the dynamic magnetoelectric couplings for the non-reciprocal directional dichroism in BiFeO 3

DOE PAGES

Kezsmarki, I.; Fishman, Randy Scott

2016-04-18

Due to the complicated magnetic and crystallographic structures of BiFeO 3, its magnetoelectric (ME) couplings and microscopic model Hamiltonian remain poorly understood. By employing a firstprinciples approach, we uncover all possibleMEcouplings associated with the spin-current (SC) and exchange-striction (ES) polarizations, and construct an appropriate Hamiltonian for the long-range spin-cycloid in BiFeO 3. First-principles calculations are used to understand the microscopic origins of theMEcouplings.Wefind that inversion symmetries broken by ferroelectric and antiferroelectric distortions induce the SC and the ES polarizations, which cooperatively produce the dynamicME effects in BiFeO 3. A model motivated by first principles reproduces the absorption difference of counter-propagatingmore » light beams called non-reciprocal directional dichroism. The current paper focuses on the spin-driven (SD) polarizations produced by a dynamic electric field, i.e. the dynamic MEcouplings. Due to the inertial properties of Fe, the dynamic SD polarizations differ significantly from the static SD polarizations. Our systematic approach can be generally applied to any multiferroic material, laying the foundation for revealing hiddenMEcouplings on the atomic scale and for exploiting opticalMEeffects in the next generation of technological devices such as optical diodes.« less

Genetic signatures of ecological diversity along an urbanization gradient.

PubMed

Kelly, Ryan P; O'Donnell, James L; Lowell, Natalie C; Shelton, Andrew O; Samhouri, Jameal F; Hennessey, Shannon M; Feist, Blake E; Williams, Gregory D

2016-01-01

Despite decades of work in environmental science and ecology, estimating human influences on ecosystems remains challenging. This is partly due to complex chains of causation among ecosystem elements, exacerbated by the difficulty of collecting biological data at sufficient spatial, temporal, and taxonomic scales. Here, we demonstrate the utility of environmental DNA (eDNA) for quantifying associations between human land use and changes in an adjacent ecosystem. We analyze metazoan eDNA sequences from water sampled in nearshore marine eelgrass communities and assess the relationship between these ecological communities and the degree of urbanization in the surrounding watershed. Counter to conventional wisdom, we find strongly increasing richness and decreasing beta diversity with greater urbanization, and similar trends in the diversity of life histories with urbanization. We also find evidence that urbanization influences nearshore communities at local (hundreds of meters) rather than regional (tens of km) scales. Given that different survey methods sample different components of an ecosystem, we then discuss the advantages of eDNA-which we use here to detect hundreds of taxa simultaneously-as a complement to traditional ecological sampling, particularly in the context of broad ecological assessments where exhaustive manual sampling is impractical. Genetic data are a powerful means of uncovering human-ecosystem interactions that might otherwise remain hidden; nevertheless, no sampling method reveals the whole of a biological community.

Phylogenomics and species delimitation of a complex radiation of Neotropical suboscine birds (Pachyramphus).

PubMed

Musher, Lukas J; Cracraft, Joel

2018-01-01

Phylogeographic studies within the Neotropics continue to uncover hidden diversity, the extent of which remains poorly known. In birds, molecular studies are producing evidence that species-level diversity is substantially underestimated. Many avian taxa comprise large complexes of subspecies that often represent species-level taxa by various criteria. One such group of Neotropical suboscine birds, the becards (Pachyramphus), ranges from Argentina through northern Mexico. Their taxonomic limits have been complex and controversial as the genus has bounced around a number of suboscine families. Additionally, the phylogenetic relationships within Pachyramphus are unresolved due to insufficient sampling of taxa and populations across species' ranges. We used target capture of ultraconserved elements for 62 individuals representing 42 taxa, and sequenced two mitochondrial genes and two nuclear introns covering 265 individuals of 51 taxa, including all recognized species, resulting in the most densely and completely sampled phylogenetic hypothesis for Pachyramphus to date. We delimited species using a traditional taxonomic approach and then tested them under a Bayesian multi-species coalescent framework. In doing so, we provide evidence for multiple young, previously undetected evolutionary lineages within Pachyramphus. Deep, well-supported branches and a high number of intraspecific lineages across the tree suggest that at least 50% of species diversity may be unrecognized. Copyright © 2017 Elsevier Inc. All rights reserved.

A persistent circhoral ultradian rhythm is identified in human core temperature.

PubMed

Lindsley, G; Dowse, H B; Burgoon, P W; Kolka, M A; Stephenson, L A

1999-01-01

There have been inconclusive reports of intermittent rhythmic fluctuations in human core temperature, with the fluctuations having a period of about an hour. However, there has been no definitive demonstration of the phenomenon. This is likely due to the intermittency and seeming instability of the events. They have been assumed to be secondary rather than autonomous phenomena, putatively arising from the oscillation between rapid eye movement (REM) and non-REM (NREM) sleep. In this study, we report identification of a clear, persistent circhoral ultradian rhythm in core temperature with a period for this study sample of 64 +/- 8 minutes. It appeared simultaneously with an intact circadian core temperature rhythm, persisted despite complex perturbations in core temperature brought about by the sequelae of 40 h of sleep deprivation, and could not be attributed to sleep stage alternation or other endogenous or exogenous factors. Analysis of power spectra using the maximum entropy spectral analysis (MESA) method, which can uncover hidden rhythmicities, demonstrated that the apparent intermittency of the rhythm is due to periodic interference of this rhythm by other rhythmic events. The persistence of this oscillation suggests that, in this system as in the endocrine system, circhoral regulation is an integral component of thermoregulatory control. Identifying the source and functional role of this novel rhythm warrants further work.

Professionalism in global, personalized cancer care: restoring authenticity and integrity.

PubMed

Surbone, Antonella

2013-01-01

Personalized medicine is revolutionizing cancer care and creating new expectations among oncologists and patients. At present the benefit is still marginal, however, and must be understood as incremental. In addition, cultural and resource disparities limit the sustainability of new cancer therapies on a global scale. Adequate instruments are needed to enable our exercise of sound and honest judgment in distinguishing breakthrough treatments from those that yield only marginal or doubtful improvements, and to develop strategies for formulation and correct application of balanced guidelines for sustainable cancer care. Professionalism requires that the acquisition of knowledge and skills go hand in hand with moral education in the intellectual virtues of humility, perseverance, adaptability, communicativeness, and commitment to resist self-deception or conflicts of interest. Hidden curricula undermine the moral values of medicine: these must be understood and uncovered. We should possess a special body of knowledge, skills, and values that allow us to change our practices when appropriate and to be stewards of society's limited resources through proper communication with our patients and families. In the era of personalized oncology and global issues of sustainability, professional authenticity and integrity in cancer clinical practice are key to bridging the gaps between true and false expectations of patients and the public.

Natural Products from Marine Fungi—Still an Underrepresented Resource

PubMed Central

Imhoff, Johannes F.

2016-01-01

Marine fungi represent a huge potential for new natural products and an increased number of new metabolites have become known over the past years, while much of the hidden potential still needs to be uncovered. Representative examples of biodiversity studies of marine fungi and of natural products from a diverse selection of marine fungi from the author’s lab are highlighting important aspects of this research. If one considers the huge phylogenetic diversity of marine fungi and their almost ubiquitous distribution, and realizes that most of the published work on secondary metabolites of marine fungi has focused on just a few genera, strictly speaking Penicillium, Aspergillus and maybe also Fusarium and Cladosporium, the diversity of marine fungi is not adequately represented in investigations on their secondary metabolites and the less studied species deserve special attention. In addition to results on recently discovered new secondary metabolites of Penicillium species, the diversity of fungi in selected marine habitats is highlighted and examples of groups of secondary metabolites produced by representatives of a variety of different genera and their bioactivities are presented. Special focus is given to the production of groups of derivatives of metabolites by the fungi and to significant differences in biological activities due to small structural changes. PMID:26784209

Chinese Interpreting Studies: a data-driven analysis of a dynamic field of enquiry

PubMed Central

Pekelis, Leonid

2015-01-01

Over the five decades since its beginnings, Chinese Interpreting Studies (CIS) has evolved into a dynamic field of academic enquiry with more than 3,500 scholars and 4,200 publications. Using quantitative and qualitative analysis, this scientometric study delves deep into CIS citation data to examine some of the noteworthy trends and patterns of behavior in the field: how can the field’s progress be quantified by means of citation analysis? Do its authors tend repeatedly to cite ‘classic’ papers or are they more drawn to their colleagues’ latest research? What different effects does the choice of empirical vs. theoretical research have on the use of citations in the various research brackets? The findings show that the field is steadily moving forward with new papers continuously being cited, although a number of influential papers stand out, having received a stream of citations in all the years examined. CIS scholars also have a tendency to cite much older English than Chinese publications across all document types, and empirical research has the greatest influence on the citation behavior of doctoral scholars, while theoretical studies have the largest impact on that of article authors. The goal of this study is to demonstrate the merits of blending quantitative and qualitative analyses to uncover hidden trends. PMID:26401459

Beyond Fractals and 1/f Noise: Multifractal Analysis of Complex Physiological Time Series

NASA Astrophysics Data System (ADS)

Ivanov, Plamen Ch.; Amaral, Luis A. N.; Ashkenazy, Yosef; Stanley, H. Eugene; Goldberger, Ary L.; Hausdorff, Jeffrey M.; Yoneyama, Mitsuru; Arai, Kuniharu

2001-03-01

We investigate time series with 1/f-like spectra generated by two physiologic control systems --- the human heartbeat and human gait. We show that physiological fluctuations exhibit unexpected ``hidden'' structures often described by scaling laws. In particular, our studies indicate that when analyzed on different time scales the heartbeat fluctuations exhibit cascades of branching patterns with self-similar (fractal) properties, characterized by long-range power-law anticorrelations. We find that these scaling features change during sleep and wake phases, and with pathological perturbations. Further, by means of a new wavelet-based technique, we find evidence of multifractality in the healthy human heartbeat even under resting conditions, and show that the multifractal character and nonlinear properties of the healthy heart are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure. In contrast to the heartbeat, we find that the interstride interval time series of healthy human gait, a voluntary process under neural regulation, is described by a single fractal dimension (such as classical 1/f noise) indicating monofractal behavior. Thus our approach can help distinguish physiological and physical signals with comparable frequency spectra and two-point correlations, and guide modeling of their control mechanisms.

Implications of the measured angular anisotropy at the hidden order transition of URu2Si2

NASA Astrophysics Data System (ADS)

Chandra, P.; Coleman, P.; Flint, R.; Trinh, J.; Ramirez, A. P.

2018-05-01

The heavy fermion compound URu2Si2 continues to attract great interest due to the long-unidentified nature of the hidden order that develops below 17.5 K. Here we discuss the implications of an angular survey of the linear and nonlinear susceptibility of URu2Si2 in the vicinity of the hidden order transition [1]. While the anisotropic nature of spin fluctuations and low-temperature quasiparticles was previously established, our recent results suggest that the order parameter itself has intrinsic Ising anisotropy, and that moreover this anisotropy extends far above the hidden order transition. Consistency checks and subsequent questions for future experimental and theoretical studies of hidden order are discussed.

A Self-Organizing Incremental Spatiotemporal Associative Memory Networks Model for Problems with Hidden State

PubMed Central

2016-01-01

Identifying the hidden state is important for solving problems with hidden state. We prove any deterministic partially observable Markov decision processes (POMDP) can be represented by a minimal, looping hidden state transition model and propose a heuristic state transition model constructing algorithm. A new spatiotemporal associative memory network (STAMN) is proposed to realize the minimal, looping hidden state transition model. STAMN utilizes the neuroactivity decay to realize the short-term memory, connection weights between different nodes to represent long-term memory, presynaptic potentials, and synchronized activation mechanism to complete identifying and recalling simultaneously. Finally, we give the empirical illustrations of the STAMN and compare the performance of the STAMN model with that of other methods. PMID:27891146

Infinite hidden conditional random fields for human behavior analysis.

PubMed

Bousmalis, Konstantinos; Zafeiriou, Stefanos; Morency, Louis-Philippe; Pantic, Maja

2013-01-01

Hidden conditional random fields (HCRFs) are discriminative latent variable models that have been shown to successfully learn the hidden structure of a given classification problem (provided an appropriate validation of the number of hidden states). In this brief, we present the infinite HCRF (iHCRF), which is a nonparametric model based on hierarchical Dirichlet processes and is capable of automatically learning the optimal number of hidden states for a classification task. We show how we learn the model hyperparameters with an effective Markov-chain Monte Carlo sampling technique, and we explain the process that underlines our iHCRF model with the Restaurant Franchise Rating Agencies analogy. We show that the iHCRF is able to converge to a correct number of represented hidden states, and outperforms the best finite HCRFs--chosen via cross-validation--for the difficult tasks of recognizing instances of agreement, disagreement, and pain. Moreover, the iHCRF manages to achieve this performance in significantly less total training, validation, and testing time.

Sustained response with ixekizumab treatment of moderate-to-severe psoriasis with scalp involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2, UNCOVER-3).

PubMed

Reich, Kristian; Leonardi, Craig; Lebwohl, Mark; Kerdel, Francisco; Okubo, Yukari; Romiti, Ricardo; Goldblum, Orin; Dennehy, Ellen B; Kerr, Lisa; Sofen, Howard

2017-06-01

Scalp is a frequently affected and difficult-to-treat area in psoriasis patients. We assessed the efficacy of ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI). In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg bi-weekly etanercept through Week 12. Patients entering the open-label long-term extension (LTE) (UNCOVER-3) received ixekizumab Q4W; UNCOVER-1 and UNCOVER-2 included a blinded maintenance period in which static physician global assessment (sPGA) 0/1 responders were re-randomized to placebo, ixekizumab Q4W, or 80 mg ixekizumab every 12 weeks (Q12W) through Week 60. In patients with moderate-to-severe psoriasis with baseline scalp involvement, PSSI 90 and 100 were achieved at Week 12 in higher percentages of patients treated with ixekizumab Q2W (81.7% and 74.6%) or ixekizumab Q4W (75.6% and 68.9%) compared with patients treated with placebo (7.6% and 6.7%; p < .001 each ixekizumab arm versus placebo) or etanercept (55.5% and 48.1%; p < .001 each ixekizumab arm versus etanercept). These outcomes were maintained through Week 60 of the maintenance (UNCOVER-1 and UNCOVER-2) and LTE (UNCOVER-3) period in patients who continued on ixekizumab Q4W. Ixekizumab was efficacious in treating scalp psoriasis in patients with moderate-to-severe psoriasis, with most patients achieving complete or near-complete resolution of scalp psoriasis and maintaining this response over 60 weeks.

Bell's theorem and the problem of decidability between the views of Einstein and Bohr.

PubMed

Hess, K; Philipp, W

2001-12-04

Einstein, Podolsky, and Rosen (EPR) have designed a gedanken experiment that suggested a theory that was more complete than quantum mechanics. The EPR design was later realized in various forms, with experimental results close to the quantum mechanical prediction. The experimental results by themselves have no bearing on the EPR claim that quantum mechanics must be incomplete nor on the existence of hidden parameters. However, the well known inequalities of Bell are based on the assumption that local hidden parameters exist and, when combined with conflicting experimental results, do appear to prove that local hidden parameters cannot exist. This fact leaves only instantaneous actions at a distance (called "spooky" by Einstein) to explain the experiments. The Bell inequalities are based on a mathematical model of the EPR experiments. They have no experimental confirmation, because they contradict the results of all EPR experiments. In addition to the assumption that hidden parameters exist, Bell tacitly makes a variety of other assumptions; for instance, he assumes that the hidden parameters are governed by a single probability measure independent of the analyzer settings. We argue that the mathematical model of Bell excludes a large set of local hidden variables and a large variety of probability densities. Our set of local hidden variables includes time-like correlated parameters and a generalized probability density. We prove that our extended space of local hidden variables does permit derivation of the quantum result and is consistent with all known experiments.

Hidden attractors in dynamical systems

NASA Astrophysics Data System (ADS)

Dudkowski, Dawid; Jafari, Sajad; Kapitaniak, Tomasz; Kuznetsov, Nikolay V.; Leonov, Gennady A.; Prasad, Awadhesh

2016-06-01

Complex dynamical systems, ranging from the climate, ecosystems to financial markets and engineering applications typically have many coexisting attractors. This property of the system is called multistability. The final state, i.e., the attractor on which the multistable system evolves strongly depends on the initial conditions. Additionally, such systems are very sensitive towards noise and system parameters so a sudden shift to a contrasting regime may occur. To understand the dynamics of these systems one has to identify all possible attractors and their basins of attraction. Recently, it has been shown that multistability is connected with the occurrence of unpredictable attractors which have been called hidden attractors. The basins of attraction of the hidden attractors do not touch unstable fixed points (if exists) and are located far away from such points. Numerical localization of the hidden attractors is not straightforward since there are no transient processes leading to them from the neighborhoods of unstable fixed points and one has to use the special analytical-numerical procedures. From the viewpoint of applications, the identification of hidden attractors is the major issue. The knowledge about the emergence and properties of hidden attractors can increase the likelihood that the system will remain on the most desirable attractor and reduce the risk of the sudden jump to undesired behavior. We review the most representative examples of hidden attractors, discuss their theoretical properties and experimental observations. We also describe numerical methods which allow identification of the hidden attractors.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction.

PubMed

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-05-15

Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction

PubMed Central

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-01-01

Background/Aims Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. Methods A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. Results The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Conclusions Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs. PMID:28208003

77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental... review of the uncovered finished water reservoir requirement in the Long Term 2 Enhanced Surface Water... uncovered finished water reservoir requirement and the agency's Six Year Review process. EPA also plans to...

The Hidden Curriculum in Distance Education: An Updated View.

ERIC Educational Resources Information Center

Anderson, Terry

2001-01-01

Addressing recent criticism of distance education, explores the distinctive hidden curriculum (supposed "real" agenda) of distance education, focusing on both its positive and negative expressions. Also offers an updated view of the hidden curriculum of traditional, campus-based education, grounded in an emerging worldwide context of broadening…

77 FR 8253 - Notice of Proposed Settlement Agreement and Opportunity for Public Comment: Hidden Lane Landfill...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9631-3] Notice of Proposed Settlement Agreement and Opportunity for Public Comment: Hidden Lane Landfill Superfund Site ACTION: Notice. SUMMARY: In accordance... (``DOJ'') on behalf of EPA, in connection with the Hidden Lane Landfill Superfund Site, Sterling, Loudoun...

Hidden Curriculum as One of Current Issue of Curriculum

ERIC Educational Resources Information Center

Alsubaie, Merfat Ayesh

2015-01-01

There are several issues in the education system, especially in the curriculum field that affect education. Hidden curriculum is one of current controversial curriculum issues. Many hidden curricular issues are the result of assumptions and expectations that are not formally communicated, established, or conveyed within the learning environment.…

Hidden Variable Theories and Quantum Nonlocality

ERIC Educational Resources Information Center

Boozer, A. D.

2009-01-01

We clarify the meaning of Bell's theorem and its implications for the construction of hidden variable theories by considering an example system consisting of two entangled spin-1/2 particles. Using this example, we present a simplified version of Bell's theorem and describe several hidden variable theories that agree with the predictions of…

Building Simple Hidden Markov Models. Classroom Notes

ERIC Educational Resources Information Center

Ching, Wai-Ki; Ng, Michael K.

2004-01-01

Hidden Markov models (HMMs) are widely used in bioinformatics, speech recognition and many other areas. This note presents HMMs via the framework of classical Markov chain models. A simple example is given to illustrate the model. An estimation method for the transition probabilities of the hidden states is also discussed.

Seuss's Butter Battle Book: Is There Hidden Harm?

ERIC Educational Resources Information Center

Van Cleaf, David W.; Martin, Rita J.

1986-01-01

Examines whether elementary school children relate to the "harmful hidden message" about nuclear war in Dr. Seuss's THE BUTTER BATTLE BOOK. After ascertaining the children's cognitive level, they participated in activities to find hidden meanings in stories, including Seuss's book. Students failed to identify the nuclear war message in…

Comment on 'All quantum observables in a hidden-variable model must commute simultaneously'

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagata, Koji

Malley discussed [Phys. Rev. A 69, 022118 (2004)] that all quantum observables in a hidden-variable model for quantum events must commute simultaneously. In this comment, we discuss that Malley's theorem is indeed valid for the hidden-variable theoretical assumptions, which were introduced by Kochen and Specker. However, we give an example that the local hidden-variable (LHV) model for quantum events preserves noncommutativity of quantum observables. It turns out that Malley's theorem is not related to the LHV model for quantum events, in general.

[Probabilities cannot be calculated retrospectively--not even in the courtroom].

PubMed

van Gijn, J

2005-12-24

Chance events are part of everyday life, but coincidence of diseases often raises suspicions about hidden causes, for example when power lines are blamed for the geographical clustering of cancer. Recently, criminal procedures in the Netherlands have revolved around the question of whether statistical 'predictions' are a valid reason to hold a hospital nurse accountable for the occurrence of excess deaths during her duty hours, or a kindergarten employee for unexplained respiratory problems in several infants. In both cases, the appeals court judges did not accept the statistical 'argument' in the absence of other evidence. In the UK, however, Sally Clark's initial life sentence for the double murder of her 2 babies was largely based on 'probabilities in retrospect', put forward by the paediatrician Sir Roy Meadow as an expert witness. 4 years later she was acquitted, whereas Meadow was struck off the medical register on a charge of professional misconduct. There is no Bayesian or other mathematical solution to the problem of chance events. Only the detection of causal factors that are plausible and supported by new evidence can help to reinterpret coincidences as relationships. Scrupulous reasoning about probabilities is required, not only of physicians but also of judges and politicians.

Bayesian networks for maritime traffic accident prevention: benefits and challenges.

PubMed

Hänninen, Maria

2014-12-01

Bayesian networks are quantitative modeling tools whose applications to the maritime traffic safety context are becoming more popular. This paper discusses the utilization of Bayesian networks in maritime safety modeling. Based on literature and the author's own experiences, the paper studies what Bayesian networks can offer to maritime accident prevention and safety modeling and discusses a few challenges in their application to this context. It is argued that the capability of representing rather complex, not necessarily causal but uncertain relationships makes Bayesian networks an attractive modeling tool for the maritime safety and accidents. Furthermore, as the maritime accident and safety data is still rather scarce and has some quality problems, the possibility to combine data with expert knowledge and the easy way of updating the model after acquiring more evidence further enhance their feasibility. However, eliciting the probabilities from the maritime experts might be challenging and the model validation can be tricky. It is concluded that with the utilization of several data sources, Bayesian updating, dynamic modeling, and hidden nodes for latent variables, Bayesian networks are rather well-suited tools for the maritime safety management and decision-making. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimizing Experimental Design for Comparing Models of Brain Function

PubMed Central

Daunizeau, Jean; Preuschoff, Kerstin; Friston, Karl; Stephan, Klaas

2011-01-01

This article presents the first attempt to formalize the optimization of experimental design with the aim of comparing models of brain function based on neuroimaging data. We demonstrate our approach in the context of Dynamic Causal Modelling (DCM), which relates experimental manipulations to observed network dynamics (via hidden neuronal states) and provides an inference framework for selecting among candidate models. Here, we show how to optimize the sensitivity of model selection by choosing among experimental designs according to their respective model selection accuracy. Using Bayesian decision theory, we (i) derive the Laplace-Chernoff risk for model selection, (ii) disclose its relationship with classical design optimality criteria and (iii) assess its sensitivity to basic modelling assumptions. We then evaluate the approach when identifying brain networks using DCM. Monte-Carlo simulations and empirical analyses of fMRI data from a simple bimanual motor task in humans serve to demonstrate the relationship between network identification and the optimal experimental design. For example, we show that deciding whether there is a feedback connection requires shorter epoch durations, relative to asking whether there is experimentally induced change in a connection that is known to be present. Finally, we discuss limitations and potential extensions of this work. PMID:22125485

Flammulina velutipes polysaccharides improve scopolamine-induced learning and memory impairment in mice by modulating gut microbiota composition.

PubMed

Su, Anxiang; Yang, Wenjian; Zhao, Liyan; Pei, Fei; Yuan, Biao; Zhong, Lei; Ma, Gaoxing; Hu, Qiuhui

2018-03-01

Flammulina velutipes polysaccharides (FVP) have been proved to be effective in improving learning and memory impairment in mice. However, their underlying mechanism remains unclear. The aim of this study was to investigate the relationship between memory improvement and gut microbiota regulation of FVP. The results showed a significant decrease in the relative abundances of Clostridia and Bacilli but a significant increase in Bacteroidia, Erysipelotrichia and Actinobacteria in the FVP-treated group versus the control group. Fecal microbiota transplantation of mice with 'FVP microbiota' derived from FVP-fed mice resulted in improved learning and memory function compared to colonization with 'common microbiota' derived from control individuals. FVP and 'FVP microbiota' significantly increased the numbers of platform crossings and the swimming distance of mice in the probe test and decreased the escape latency and total swimming distance of mice in the hidden platform test. Moreover, FVP and 'FVP microbiota' regulated cytokines, such as IL-1β, TNF-α, IL-6 and IL-10, suggesting a mechanism involving the suppression of neuroinflammation. This study indicated that the regulation of the gut microbiome may have a causal role in improving scopolamine-induced impairment of learning and memory.

Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks

PubMed Central

Vanvinckenroye, Amaury; Vandewalle, Gilles; Chellappa, Sarah L.

2016-01-01

Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states. PMID:26885400

Some Thermodynamic Considerations on the Physical and Quantum Nature of Space and Time

NASA Technical Reports Server (NTRS)

Sohrab, Siavash H.; Piltch, Nancy (Technical Monitor)

2000-01-01

It is suggested that the Planck h = m(sub k)c Lambda(sub k) and the Boltzmann k = m(sub k)c nu(sub k)Constants have stochastic foundation. It is further suggested that a body of fluid at equilibrium is composed of a spectrum of molecular clusters (energy levels) the size of which are governed by the Maxwell-Boltzmann distribution function. Brownian motions are attributed to equilibrium between suspensions and molecular clusters. Atomic (molecular) transition between different size atomic- (molecular-) clusters (energy levels) is shown to result in emission/absorption of energy in accordance with Bohr's theory of atomic spectra. Physical space is identified as a tachyonic fluid that is Dirac's stochastic ether or de Broglie's hidden thermostat. Compressibility of physical space, in accordance with Planck's compressible ether, is shown to result in the Lorentz-Fitzgerald contraction, thus providing a causal explanation of relativistic effect in accordance with the perceptions of Poincare and Lorentz. The invariant Schrodinger equation is derived from the invariant Bernoulli equation for incompressible potential flow. Following Heisenberg a temporal uncertainty relation is introduced as Delta(nu(sub Beta)) Delta(Rho(sub Beta)) > = k.

Variational Bayesian identification and prediction of stochastic nonlinear dynamic causal models.

PubMed

Daunizeau, J; Friston, K J; Kiebel, S J

2009-11-01

In this paper, we describe a general variational Bayesian approach for approximate inference on nonlinear stochastic dynamic models. This scheme extends established approximate inference on hidden-states to cover: (i) nonlinear evolution and observation functions, (ii) unknown parameters and (precision) hyperparameters and (iii) model comparison and prediction under uncertainty. Model identification or inversion entails the estimation of the marginal likelihood or evidence of a model. This difficult integration problem can be finessed by optimising a free-energy bound on the evidence using results from variational calculus. This yields a deterministic update scheme that optimises an approximation to the posterior density on the unknown model variables. We derive such a variational Bayesian scheme in the context of nonlinear stochastic dynamic hierarchical models, for both model identification and time-series prediction. The computational complexity of the scheme is comparable to that of an extended Kalman filter, which is critical when inverting high dimensional models or long time-series. Using Monte-Carlo simulations, we assess the estimation efficiency of this variational Bayesian approach using three stochastic variants of chaotic dynamic systems. We also demonstrate the model comparison capabilities of the method, its self-consistency and its predictive power.

Nonlinearity without superluminality

NASA Astrophysics Data System (ADS)

Kent, Adrian

2005-07-01

Quantum theory is compatible with special relativity. In particular, though measurements on entangled systems are correlated in a way that cannot be reproduced by local hidden variables, they cannot be used for superluminal signaling. As Czachor, Gisin, and Polchinski pointed out, this is not generally true of general nonlinear modifications of the Schrödinger equation. Excluding superluminal signaling has thus been taken to rule out most nonlinear versions of quantum theory. The no-superluminal-signaling constraint has also been used for alternative derivations of the optimal fidelities attainable for imperfect quantum cloning and other operations. These results apply to theories satisfying the rule that their predictions for widely separated and slowly moving entangled systems can be approximated by nonrelativistic equations of motion with respect to a preferred time coordinate. This paper describes a natural way in which this rule might fail to hold. In particular, it is shown that quantum readout devices which display the values of localized pure states need not allow superluminal signaling, provided that the devices display the values of the states of entangled subsystems as defined in a nonstandard, although natural, way. It follows that any locally defined nonlinear evolution of pure states can be made consistent with Minkowski causality.

Inference for dynamics of continuous variables: the extended Plefka expansion with hidden nodes

NASA Astrophysics Data System (ADS)

Bravi, B.; Sollich, P.

2017-06-01

We consider the problem of a subnetwork of observed nodes embedded into a larger bulk of unknown (i.e. hidden) nodes, where the aim is to infer these hidden states given information about the subnetwork dynamics. The biochemical networks underlying many cellular and metabolic processes are important realizations of such a scenario as typically one is interested in reconstructing the time evolution of unobserved chemical concentrations starting from the experimentally more accessible ones. We present an application to this problem of a novel dynamical mean field approximation, the extended Plefka expansion, which is based on a path integral description of the stochastic dynamics. As a paradigmatic model we study the stochastic linear dynamics of continuous degrees of freedom interacting via random Gaussian couplings. The resulting joint distribution is known to be Gaussian and this allows us to fully characterize the posterior statistics of the hidden nodes. In particular the equal-time hidden-to-hidden variance—conditioned on observations—gives the expected error at each node when the hidden time courses are predicted based on the observations. We assess the accuracy of the extended Plefka expansion in predicting these single node variances as well as error correlations over time, focussing on the role of the system size and the number of observed nodes.

Follow that fish: Uncovering the hidden blue economy in coral reef fisheries

PubMed Central

Teneva, Lida; Kittinger, John N.

2017-01-01

Despite their importance for human well-being, nearshore fisheries are often data poor, undervalued, and underappreciated in policy and development programs. We assess the value chain for nearshore Hawaiian coral reef fisheries, mapping post-catch distribution and disposition, and quantifying associated monetary, food security, and cultural values. We estimate that the total annual value of the nearshore fishery in Hawaiʻi is $10.3-$16.4 million, composed of non-commercial ($7.2-$12.9 million) and commercial ($2.97 million licensed + $148,500-$445,500 unlicensed) catch. Hawaii’s nearshore fisheries provide >7 million meals annually, with most (>5 million) from the non-commercial sector. Over a third (36%) of meals were planktivores, 26% piscivores, 21% primary consumers, and 18% secondary consumers. Only 62% of licensed commercial catch is accounted for in purchase reports, leaving 38% of landings unreported in sales. Value chains are complex, with major buyers for the commercial fishery including grocery stores (66%), retailers (19%), wholesalers (14%), and restaurants (<1%), who also trade and sell amongst themselves. The bulk of total nearshore catch (72–74%) follows a short value chain, with non-commercial fishers keeping catch for household consumption or community sharing. A small amount (~37,000kg) of reef fish—the equivalent of 1.8% of local catch—is imported annually into Hawaiʻi, 23,000kg of which arrives as passenger luggage on commercial flights from Micronesia. Evidence of exports to the US mainland exists, but is unquantifiable given existing data. Hawaiian nearshore fisheries support fundamental cultural values including subsistence, activity, traditional knowledge, and social cohesion. These small-scale coral reef fisheries provide large-scale benefits to the economy, food security, and cultural practices of Hawaiʻi, underscoring the need for sustainable management. This research highlights the value of information on the value chain for small-scale production systems, making the hidden economy of these fisheries visible and illuminating a range of conservation interventions applicable to Hawaiʻi and beyond. PMID:28771508

Covered versus uncovered self-expandable metal stents for malignant biliary strictures: A meta-analysis and systematic review.

PubMed

Moole, Harsha; Bechtold, Matthew L; Cashman, Micheal; Volmar, Fritz H; Dhillon, Sonu; Forcione, David; Taneja, Deepak; Puli, Srinivas R

2016-09-01

Self-expandable metal stents (SEMS) are used for palliating inoperable malignant biliary strictures. It is unclear if covered metal stents are superior to uncovered metal stents in these patients. We compared clinical outcomes in patients with covered and uncovered stents. Studies using covered and uncovered metallic stents for palliation in patients with malignant biliary stricture were reviewed. Articles were searched in MEDLINE, PubMed, and Ovid journals. Fixed and random effects models were used to calculate the pooled proportions. Initial search identified 1436 reference articles, of which 132 were selected and reviewed. Thirteen studies (n = 2239) for covered and uncovered metallic stents which met the inclusion criteria were included in this analysis. Odds ratio for stent occlusion rates in covered vs. uncovered stents was 0.79 (95 % CI = 0.65 to 0.96). Survival benefit in patients with covered vs. uncovered stents showed the odds ratio to be 1.29 (95 % CI = 0.95 to 1.74). Pooled odds ratio for migration of covered vs. uncovered stents was 9.9 (95 % CI = 4.5 to 22.3). Covered stents seemed to have significantly lesser occlusion rates, increased odds of migration, and increased odds of pancreatitis compared to uncovered stents. There was no statistically significant difference in the survival benefit, overall adverse event rate, and patency period of covered vs. uncovered metal stents in patients with malignant biliary strictures.

Increased taxon sampling reveals thousands of hidden orthologs in flatworms

PubMed Central

2017-01-01

Gains and losses shape the gene complement of animal lineages and are a fundamental aspect of genomic evolution. Acquiring a comprehensive view of the evolution of gene repertoires is limited by the intrinsic limitations of common sequence similarity searches and available databases. Thus, a subset of the gene complement of an organism consists of hidden orthologs, i.e., those with no apparent homology to sequenced animal lineages—mistakenly considered new genes—but actually representing rapidly evolving orthologs or undetected paralogs. Here, we describe Leapfrog, a simple automated BLAST pipeline that leverages increased taxon sampling to overcome long evolutionary distances and identify putative hidden orthologs in large transcriptomic databases by transitive homology. As a case study, we used 35 transcriptomes of 29 flatworm lineages to recover 3427 putative hidden orthologs, some unidentified by OrthoFinder and HaMStR, two common orthogroup inference algorithms. Unexpectedly, we do not observe a correlation between the number of putative hidden orthologs in a lineage and its “average” evolutionary rate. Hidden orthologs do not show unusual sequence composition biases that might account for systematic errors in sequence similarity searches. Instead, gene duplication with divergence of one paralog and weak positive selection appear to underlie hidden orthology in Platyhelminthes. By using Leapfrog, we identify key centrosome-related genes and homeodomain classes previously reported as absent in free-living flatworms, e.g., planarians. Altogether, our findings demonstrate that hidden orthologs comprise a significant proportion of the gene repertoire in flatworms, qualifying the impact of gene losses and gains in gene complement evolution. PMID:28400424

A Rose By Other Names: Some General Musings on Lawrence and Colleagues' Hidden Curriculum Scoping Review.

PubMed

Hafferty, Frederic W; Martimianakis, Maria Athina

2017-11-07

In this Commentary, the authors explore the scoping review by Lawrence and colleagues by challenging their conclusion that with over 25 years' worth of "ambiguous and seemingly ubiquitous use" of the hidden curriculum construct in health professions education scholarship, it is time to either move to a more uniform definitional foundation or abandon the term altogether. The commentary authors counter these remedial propositions by foregrounding the importance of theoretical diversity and the conceptual richness afforded when the hidden curriculum construct is used as an entry point for studying the interstitial space between the formal and a range of other-than-formal domains of learning. Further, they document how tightly-delimited scoping strategies fail to capture the wealth of educational scholarship that operates within a hidden curriculum framework, including "hidden" hidden curriculum articles, studies that employ alternative constructs, and investigations that target important tacit socio-cultural influences on learners and faculty without formally deploying the term. They offer examples of how the hidden curriculum construct, while undergoing significant transformation in its application within the field of health professions education, has created the conceptual foundation for the application of a number of critical perspectives that make visible the field's political investments in particular forms of knowing and associated practices. Finally, the commentary authors invite readers to consider the methodological promise afforded by conceptual heterogeneity, particularly strands of scholarship that resituate the hidden curriculum concept within the magically expansive dance of social relationships, social learning, and social life that form the learning environments of health professions education.

FIMP dark matter freeze-in gauge mediation and hidden sector

NASA Astrophysics Data System (ADS)

Tsao, Kuo-Hsing

2018-07-01

We explore the dark matter freeze-in mechanism within the gauge mediation framework, which involves a hidden feebly interacting massive particle (FIMP) coupling feebly with the messenger fields while the messengers are still in the thermal bath. The FIMP is the fermionic component of the pseudo-moduli in a generic metastable supersymmetry (SUSY) breaking model and resides in the hidden sector. The relic abundance and the mass of the FIMP are determined by the SUSY breaking scale and the feeble coupling. The gravitino, which is the canonical dark matter candidate in the gauge mediation framework, contributes to the dark matter relic abundance along with the freeze-in of the FIMP. The hidden sector thus becomes two-component with both the FIMP and gravitino lodging in the SUSY breaking hidden sector. We point out that the ratio between the FIMP and the gravitino is determined by how SUSY breaking is communicated to the messengers. In particular when the FIMP dominates the hidden sector, the gravitino becomes the minor contributor in the hidden sector. Meanwhile, the neutralino is assumed to be both the weakly interacting massive particle dark matter candidate in the freeze-out mechanism and the lightest observable SUSY particle. We further find out the neutralino has the sub-leading contribution to the current dark matter relic density in the parameter space of our freeze-in gauge mediation model. Our result links the SUSY breaking scale in the gauge mediation framework with the FIMP freeze-in production rate leading to a natural and predicting scenario for the studies of the dark matter in the hidden sector.

Information transfer across the scales of climate variability: The effect of the 7-8 year cycle on the annual and interannual scales

NASA Astrophysics Data System (ADS)

Palus, Milan; Jajcay, Nikola; Hlinka, Jaroslav; Kravtsov, Sergey; Tsonis, Anastasios

2016-04-01

Complexity of the climate system stems not only from the fact that it is variable over a huge range of spatial and temporal scales, but also from the nonlinear character of the climate system that leads to interactions of dynamics across scales. The dynamical processes on large time scales influence variability on shorter time scales. This nonlinear phenomenon of cross-scale causal interactions can be observed due to the recently introduced methodology [1] which starts with a wavelet decomposition of a multi-scale signal into quasi-oscillatory modes of a limited bandwidth, described using their instantaneous phases and amplitudes. Then their statistical associations are tested in order to search for interactions across time scales. An information-theoretic formulation of the generalized, nonlinear Granger causality [2] uncovers causal influence and information transfer from large-scale modes of climate variability with characteristic time scales from years to almost a decade to regional temperature variability on short time scales. In analyses of air temperature records from various European locations, a quasioscillatory phenomenon with the period around 7-8 years has been identified as the factor influencing variability of surface air temperature (SAT) on shorter time scales. Its influence on the amplitude of the SAT annual cycle was estimated in the range 0.7-1.4 °C and the effect on the overall variability of the SAT anomalies (SATA) leads to the changes 1.5-1.7 °C in the annual SATA means. The strongest effect of the 7-8 year cycle was observed in the winter SATA means where it reaches 4-5 °C in central European station and reanalysis data [3]. This study is supported by the Ministry of Education, Youth and Sports of the Czech Republic within the Program KONTAKT II, Project No. LH14001. [1] M. Palus, Phys. Rev. Lett. 112 078702 (2014) [2] M. Palus, M. Vejmelka, Phys. Rev. E 75, 056211 (2007) [3] N. Jajcay, J. Hlinka, S. Kravtsov, A. A. Tsonis, M. Palus, Time-scales of the European surface air temperature variability: The role of the 7-8 year cycle. Geophys. Res. Lett., in press, DOI: 10.1002/2015GL067325

Birth weight differences between those offered financial voucher incentives for verified smoking cessation and control participants enrolled in the Cessation in Pregnancy Incentives Trial (CPIT), employing an intuitive approach and a Complier Average Causal Effects (CACE) analysis.

PubMed

McConnachie, Alex; Haig, Caroline; Sinclair, Lesley; Bauld, Linda; Tappin, David M

2017-07-20

The Cessation in Pregnancy Incentives Trial (CPIT), which offered financial incentives for smoking cessation during pregnancy showed a clinically and statistically significant improvement in cessation. However, infant birth weight was not seen to be affected. This study re-examines birth weight using an intuitive and a complier average causal effects (CACE) method to uncover important information missed by intention-to-treat analysis. CPIT offered financial incentives up to £400 to pregnant smokers to quit. With incentives, 68 women (23.1%) were confirmed non-smokers at primary outcome, compared to 25 (8.7%) without incentives, a difference of 14.3% (Fisher test, p < 0.0001). For this analysis, randomised groups were split into three theoretical sub-groups: independent quitters - quit without incentives, hardened smokers - could not quit even with incentives and potential quitters - required the addition of financial incentives to quit. Viewed in this way, the overall birth weight gain with incentives is attributable only to potential quitters. We compared an intuitive approach to a CACE analysis. Mean birth weight of potential quitters in the incentives intervention group (who therefore quit) was 3338 g compared with potential quitters in the control group (who did not quit) 3193 g. The difference attributable to incentives, was 3338 - 3193 = 145 g (95% CI -617, +803). The mean difference in birth weight between the intervention and control groups was 21 g, and the difference in the proportion who managed to quit was 14.3%. Since the intervention consisted of the offer of incentives to quit smoking, the intervention was received by all women in the intervention group. However, "compliance" was successfully quitting with incentives, and the CACE analysis yielded an identical result, causal birth weight increase 21 g ÷ 0.143 = 145 g. Policy makers have great difficulty giving pregnant women money to stop smoking. This study indicates that a small clinically insignificant improvement in average birth weight is likely to hide an important clinically significant increase in infants born to pregnant smokers who want to stop but cannot achieve smoking cessation without the addition of financial voucher incentives. ISRCTN Registry, ISRCTN87508788 . Registered on 1 September 2011.

What Should We Do With a Hidden Curriculum When We Fine One?

ERIC Educational Resources Information Center

Martin, Jane R.

1976-01-01

A hidden curriculum consists of those learning states of a setting that are either unintended or intended but not openly acknowledged to the learners in the setting unless the learners are aware of them. Consciousness-raising may be the best weapon of individuals who are subject to hidden curricula. (Author/MLF)

Manifestations of Hidden Curriculum in a Community College Online Opticianry Program: An Ecological Approach

ERIC Educational Resources Information Center

Hubbard, Barry

2010-01-01

Understanding the influential factors at work within an online learning environment is a growing area of interest. Hidden or implicit expectations, skill sets, knowledge, and social process can help or hinder student achievement, belief systems, and persistence. This qualitative study investigated how hidden curricular issues transpired in an…

The Hidden Reason Behind Children's Misbehavior.

ERIC Educational Resources Information Center

Nystul, Michael S.

1986-01-01

Discusses hidden reason theory based on the assumptions that: (1) the nature of people is positive; (2) a child's most basic psychological need is involvement; and (3) a child has four possible choices in life (good somebody, good nobody, bad somebody, or severely mentally ill.) A three step approach for implementing hidden reason theory is…

Student Teaching: A Hidden Wholeness

ERIC Educational Resources Information Center

Bowman, Richard F.

2007-01-01

Productive student teachers lead learning by emergently sensing and honoring the hidden wholeness of life in classrooms. That hidden wholeness mirrors seven contextual concerns which learners reflect upon in the everydayness of classroom life: What are we going to do in class today? What am I going to have to do in class? What counts in today's…

Environmental Assessment for the Expansion of Permitted Land and Operations at the 9940 Complex and Thunder Range at Sandia National Laboratories/New Mexico

DTIC Science & Technology

2008-03-01

vivipara Hidden flower Cryptantha crassisepala Hidden flower Cryptantha fulvocanescens James’s hidden flower Cryptantha jamesii Buffalo gourd...pumila Bigbract verbena ta Verbena bractea Banana yucca ta Yucca bacca Soapweed yucca Yucca glauca Rocky Mountain zinnia Zinnia grandiflora A-9

Hidden Agendas in Marriage: Affective and Longitudinal Dimensions.

ERIC Educational Resources Information Center

Krokoff, Lowell J.

1990-01-01

Examines how couples' discussions of troublesome problems reveal hidden agendas (issues not directly discussed or explored). Finds disgust and contempt are at the core of both love and respect agendas for husbands and wives. Finds that wives' more than husbands' hidden agendas are directly predictive of how negatively they argue at home. (SR)

Driving style recognition method using braking characteristics based on hidden Markov model

PubMed Central

Wu, Chaozhong; Lyu, Nengchao; Huang, Zhen

2017-01-01

Since the advantage of hidden Markov model in dealing with time series data and for the sake of identifying driving style, three driving style (aggressive, moderate and mild) are modeled reasonably through hidden Markov model based on driver braking characteristics to achieve efficient driving style. Firstly, braking impulse and the maximum braking unit area of vacuum booster within a certain time are collected from braking operation, and then general braking and emergency braking characteristics are extracted to code the braking characteristics. Secondly, the braking behavior observation sequence is used to describe the initial parameters of hidden Markov model, and the generation of the hidden Markov model for differentiating and an observation sequence which is trained and judged by the driving style is introduced. Thirdly, the maximum likelihood logarithm could be implied from the observable parameters. The recognition accuracy of algorithm is verified through experiments and two common pattern recognition algorithms. The results showed that the driving style discrimination based on hidden Markov model algorithm could realize effective discriminant of driving style. PMID:28837580

A possible loophole in the theorem of Bell.

PubMed

Hess, K; Philipp, W

2001-12-04

The celebrated inequalities of Bell are based on the assumption that local hidden parameters exist. When combined with conflicting experimental results, these inequalities appear to prove that local hidden parameters cannot exist. This contradiction suggests to many that only instantaneous action at a distance can explain the Einstein, Podolsky, and Rosen type of experiments. We show that, in addition to the assumption that hidden parameters exist, Bell tacitly makes a variety of other assumptions that contribute to his being able to obtain the desired contradiction. For instance, Bell assumes that the hidden parameters do not depend on time and are governed by a single probability measure independent of the analyzer settings. We argue that the exclusion of time has neither a physical nor a mathematical basis but is based on Bell's translation of the concept of Einstein locality into the language of probability theory. Our additional set of local hidden variables includes time-like correlated parameters and a generalized probability density. We prove that our extended space of local hidden variables does not permit Bell-type proofs to go forward.

Reputation and Competition in a Hidden Action Model

PubMed Central

Fedele, Alessandro; Tedeschi, Piero

2014-01-01

The economics models of reputation and quality in markets can be classified in three categories. (i) Pure hidden action, where only one type of seller is present who can provide goods of different quality. (ii) Pure hidden information, where sellers of different types have no control over product quality. (iii) Mixed frameworks, which include both hidden action and hidden information. In this paper we develop a pure hidden action model of reputation and Bertrand competition, where consumers and firms interact repeatedly in a market with free entry. The price of the good produced by the firms is contractible, whilst the quality is noncontractible, hence it is promised by the firms when a contract is signed. Consumers infer future quality from all available information, i.e., both from what they know about past quality and from current prices. According to early contributions, competition should make reputation unable to induce the production of high-quality goods. We provide a simple solution to this problem by showing that high quality levels are sustained as an outcome of a stationary symmetric equilibrium. PMID:25329387

Reputation and competition in a hidden action model.

PubMed

Fedele, Alessandro; Tedeschi, Piero

2014-01-01

The economics models of reputation and quality in markets can be classified in three categories. (i) Pure hidden action, where only one type of seller is present who can provide goods of different quality. (ii) Pure hidden information, where sellers of different types have no control over product quality. (iii) Mixed frameworks, which include both hidden action and hidden information. In this paper we develop a pure hidden action model of reputation and Bertrand competition, where consumers and firms interact repeatedly in a market with free entry. The price of the good produced by the firms is contractible, whilst the quality is noncontractible, hence it is promised by the firms when a contract is signed. Consumers infer future quality from all available information, i.e., both from what they know about past quality and from current prices. According to early contributions, competition should make reputation unable to induce the production of high-quality goods. We provide a simple solution to this problem by showing that high quality levels are sustained as an outcome of a stationary symmetric equilibrium.

Photoacoustic imaging of hidden dental caries by using a bundle of hollow optical fibers

NASA Astrophysics Data System (ADS)

Koyama, Takuya; Kakino, Satoko; Matsuura, Yuji

2018-02-01

Photoacoustic imaging system using a bundle of hollow-optical fibers to detect hidden dental caries is proposed. Firstly, we fabricated a hidden caries model with a brown pigment simulating a common color of caries lesion. It was found that high frequency ultrasonic waves are generated from hidden carious part when radiating Nd:YAG laser light with a 532 nm wavelength to occlusal surface of model tooth. We calculated by Fourier transform and found that the waveform from the carious part provides frequency components of approximately from 0.5 to 1.2 MHz. Then a photoacoustic imaging system using a bundle of hollow optical fiber was fabricated for clinical applications. From intensity map of frequency components in 0.5-1.2 MHz, photoacoustic images of hidden caries in the simulated samples were successfully obtained.

On the LHC sensitivity for non-thermalised hidden sectors

NASA Astrophysics Data System (ADS)

Kahlhoefer, Felix

2018-04-01

We show under rather general assumptions that hidden sectors that never reach thermal equilibrium in the early Universe are also inaccessible for the LHC. In other words, any particle that can be produced at the LHC must either have been in thermal equilibrium with the Standard Model at some point or must be produced via the decays of another hidden sector particle that has been in thermal equilibrium. To reach this conclusion, we parametrise the cross section connecting the Standard Model to the hidden sector in a very general way and use methods from linear programming to calculate the largest possible number of LHC events compatible with the requirement of non-thermalisation. We find that even the HL-LHC cannot possibly produce more than a few events with energy above 10 GeV involving states from a non-thermalised hidden sector.

Optimization of Artificial Neural Network using Evolutionary Programming for Prediction of Cascading Collapse Occurrence due to the Hidden Failure Effect

NASA Astrophysics Data System (ADS)

Idris, N. H.; Salim, N. A.; Othman, M. M.; Yasin, Z. M.

2018-03-01

This paper presents the Evolutionary Programming (EP) which proposed to optimize the training parameters for Artificial Neural Network (ANN) in predicting cascading collapse occurrence due to the effect of protection system hidden failure. The data has been collected from the probability of hidden failure model simulation from the historical data. The training parameters of multilayer-feedforward with backpropagation has been optimized with objective function to minimize the Mean Square Error (MSE). The optimal training parameters consists of the momentum rate, learning rate and number of neurons in first hidden layer and second hidden layer is selected in EP-ANN. The IEEE 14 bus system has been tested as a case study to validate the propose technique. The results show the reliable prediction of performance validated through MSE and Correlation Coefficient (R).

Hidden charged dark matter and chiral dark radiation

NASA Astrophysics Data System (ADS)

Ko, P.; Nagata, Natsumi; Tang, Yong

2017-10-01

In the light of recent possible tensions in the Hubble constant H0 and the structure growth rate σ8 between the Planck and other measurements, we investigate a hidden-charged dark matter (DM) model where DM interacts with hidden chiral fermions, which are charged under the hidden SU(N) and U(1) gauge interactions. The symmetries in this model assure these fermions to be massless. The DM in this model, which is a Dirac fermion and singlet under the hidden SU(N), is also assumed to be charged under the U(1) gauge symmetry, through which it can interact with the chiral fermions. Below the confinement scale of SU(N), the hidden quark condensate spontaneously breaks the U(1) gauge symmetry such that there remains a discrete symmetry, which accounts for the stability of DM. This condensate also breaks a flavor symmetry in this model and Nambu-Goldstone bosons associated with this flavor symmetry appear below the confinement scale. The hidden U(1) gauge boson and hidden quarks/Nambu-Goldstone bosons are components of dark radiation (DR) above/below the confinement scale. These light fields increase the effective number of neutrinos by δNeff ≃ 0.59 above the confinement scale for N = 2, resolving the tension in the measurements of the Hubble constant by Planck and Hubble Space Telescope if the confinement scale is ≲1 eV. DM and DR continuously scatter with each other via the hidden U(1) gauge interaction, which suppresses the matter power spectrum and results in a smaller structure growth rate. The DM sector couples to the Standard Model sector through the exchange of a real singlet scalar mixing with the Higgs boson, which makes it possible to probe our model in DM direct detection experiments. Variants of this model are also discussed, which may offer alternative ways to investigate this scenario.

Nonparametric model validations for hidden Markov models with applications in financial econometrics.

PubMed

Zhao, Zhibiao

2011-06-01

We address the nonparametric model validation problem for hidden Markov models with partially observable variables and hidden states. We achieve this goal by constructing a nonparametric simultaneous confidence envelope for transition density function of the observable variables and checking whether the parametric density estimate is contained within such an envelope. Our specification test procedure is motivated by a functional connection between the transition density of the observable variables and the Markov transition kernel of the hidden states. Our approach is applicable for continuous time diffusion models, stochastic volatility models, nonlinear time series models, and models with market microstructure noise.

State Space Model with hidden variables for reconstruction of gene regulatory networks.

PubMed

Wu, Xi; Li, Peng; Wang, Nan; Gong, Ping; Perkins, Edward J; Deng, Youping; Zhang, Chaoyang

2011-01-01

State Space Model (SSM) is a relatively new approach to inferring gene regulatory networks. It requires less computational time than Dynamic Bayesian Networks (DBN). There are two types of variables in the linear SSM, observed variables and hidden variables. SSM uses an iterative method, namely Expectation-Maximization, to infer regulatory relationships from microarray datasets. The hidden variables cannot be directly observed from experiments. How to determine the number of hidden variables has a significant impact on the accuracy of network inference. In this study, we used SSM to infer Gene regulatory networks (GRNs) from synthetic time series datasets, investigated Bayesian Information Criterion (BIC) and Principle Component Analysis (PCA) approaches to determining the number of hidden variables in SSM, and evaluated the performance of SSM in comparison with DBN. True GRNs and synthetic gene expression datasets were generated using GeneNetWeaver. Both DBN and linear SSM were used to infer GRNs from the synthetic datasets. The inferred networks were compared with the true networks. Our results show that inference precision varied with the number of hidden variables. For some regulatory networks, the inference precision of DBN was higher but SSM performed better in other cases. Although the overall performance of the two approaches is compatible, SSM is much faster and capable of inferring much larger networks than DBN. This study provides useful information in handling the hidden variables and improving the inference precision.

Cryptic diversity in Ptyodactylus (Reptilia: Gekkonidae) from the northern Hajar Mountains of Oman and the United Arab Emirates uncovered by an integrative taxonomic approach

PubMed Central

Simó-Riudalbas, Marc; de Pous, Philip; Els, Johannes; Jayasinghe, Sithum; Péntek-Zakar, Erika; Wilms, Thomas; Al-Saadi, Saleh

2017-01-01

The Hajar Mountains of south-eastern Arabia form an isolated massif surrounded by the sea to the east and by a large desert to the west. As a result of their old geological origin, geographical isolation, complex topography and local climate, these mountains provide an important refuge for endemic and relict species of plants and animals. With 19 species restricted to the Hajar Mountains, reptiles are the vertebrate group with the highest level of endemicity, becoming an excellent model for understanding the patterns and processes that generate and shape diversity in this arid mountain range. The geckos of the Ptyodactylus hasselquistii species complex are the largest geckos in Arabia and are found widely distributed across the Arabian Mountains, constituting a very important component of the reptile mountain fauna. Preliminary analyses suggested that their diversity in the Hajar Mountains may be higher than expected and that their systematics should be revised. In order to tackle these questions, we inferred a nearly complete calibrated phylogeny of the genus Ptyodactylus to identify the origin of the Hajar Mountains lineages using information from two mitochondrial and four nuclear genes. Genetic variability within the Hajar Mountains was further investigated using 68 specimens of Ptyodactylus from 46 localities distributed across the entire mountain range and sequenced for the same genes as above. The molecular phylogenies and morphological analyses as well as niche comparisons indicate the presence of two very old sister cryptic species living in allopatry: one restricted to the extreme northern Hajar Mountains and described as a new species herein; the other distributed across the rest of the Hajar Mountains that can be confidently assigned to the species P. orlovi. Similar to recent findings in the geckos of the genus Asaccus, the results of the present study uncover more hidden diversity in the northern Hajar Mountains and stress once again the importance of this unique mountain range as a hot spot of biodiversity and a priority focal point for reptile conservation in Arabia. PMID:28767644

What Makes You Tick? An Empirical Study of Space Science Related Social Media Communications Using Machine Learning

NASA Astrophysics Data System (ADS)

Hwong, Y. L.; Oliver, C.; Van Kranendonk, M. J.

2016-12-01

The rise of social media has transformed the way the public engages with scientists and science organisations. `Retweet', `Like', `Share' and `Comment' are a few ways users engage with messages on Twitter and Facebook, two of the most popular social media platforms. Despite the availability of big data from these digital footprints, research into social media science communication is scant. This paper presents the results of an empirical study into the processes and outcomes of space science related social media communications using machine learning. The study is divided into two main parts. The first part is dedicated to the use of supervised learning methods to investigate the features of highly engaging messages., e.g. highly retweeted tweets and shared Facebook posts. It is hypothesised that these messages contain certain psycholinguistic features that are unique to the field of space science. We built a predictive model to forecast the engagement levels of social media posts. By using four feature sets (n-grams, psycholinguistics, grammar and social media), we were able to achieve prediction accuracies in the vicinity of 90% using three supervised learning algorithms (Naive Bayes, linear classifier and decision tree). We conducted the same experiments on social media messages from three other fields (politics, business and non-profit) and discovered several features that are exclusive to space science communications: anger, authenticity, hashtags, visual descriptions and a tentative tone. The second part of the study focuses on the extraction of topics from a corpus of texts using topic modelling. This part of the study is exploratory in nature and uses an unsupervised method called Latent Dirichlet Allocation (LDA) to uncover previously unknown topics within a large body of documents. Preliminary results indicate a strong potential of topic model algorithms to automatically uncover themes hidden within social media chatters on space related issues, with keywords such as `exoplanet', `water' and `life' being clustered together forming a topic (i.e. 'Astrobiology'). Results also demonstrate the freewheeling nature of social media conversations, while providing evidence for the role of these platforms in facilitating meaningful exchanges among science audience.

Memetic algorithms for de novo motif-finding in biomedical sequences.

PubMed

Bi, Chengpeng

2012-09-01

The objectives of this study are to design and implement a new memetic algorithm for de novo motif discovery, which is then applied to detect important signals hidden in various biomedical molecular sequences. In this paper, memetic algorithms are developed and tested in de novo motif-finding problems. Several strategies in the algorithm design are employed that are to not only efficiently explore the multiple sequence local alignment space, but also effectively uncover the molecular signals. As a result, there are a number of key features in the implementation of the memetic motif-finding algorithm (MaMotif), including a chromosome replacement operator, a chromosome alteration-aware local search operator, a truncated local search strategy, and a stochastic operation of local search imposed on individual learning. To test the new algorithm, we compare MaMotif with a few of other similar algorithms using simulated and experimental data including genomic DNA, primary microRNA sequences (let-7 family), and transmembrane protein sequences. The new memetic motif-finding algorithm is successfully implemented in C++, and exhaustively tested with various simulated and real biological sequences. In the simulation, it shows that MaMotif is the most time-efficient algorithm compared with others, that is, it runs 2 times faster than the expectation maximization (EM) method and 16 times faster than the genetic algorithm-based EM hybrid. In both simulated and experimental testing, results show that the new algorithm is compared favorably or superior to other algorithms. Notably, MaMotif is able to successfully discover the transcription factors' binding sites in the chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) data, correctly uncover the RNA splicing signals in gene expression, and precisely find the highly conserved helix motif in the transmembrane protein sequences, as well as rightly detect the palindromic segments in the primary microRNA sequences. The memetic motif-finding algorithm is effectively designed and implemented, and its applications demonstrate it is not only time-efficient, but also exhibits excellent performance while compared with other popular algorithms. Copyright © 2012 Elsevier B.V. All rights reserved.

Cryptic diversity in Ptyodactylus (Reptilia: Gekkonidae) from the northern Hajar Mountains of Oman and the United Arab Emirates uncovered by an integrative taxonomic approach.

PubMed

Simó-Riudalbas, Marc; Metallinou, Margarita; de Pous, Philip; Els, Johannes; Jayasinghe, Sithum; Péntek-Zakar, Erika; Wilms, Thomas; Al-Saadi, Saleh; Carranza, Salvador

2017-01-01

The Hajar Mountains of south-eastern Arabia form an isolated massif surrounded by the sea to the east and by a large desert to the west. As a result of their old geological origin, geographical isolation, complex topography and local climate, these mountains provide an important refuge for endemic and relict species of plants and animals. With 19 species restricted to the Hajar Mountains, reptiles are the vertebrate group with the highest level of endemicity, becoming an excellent model for understanding the patterns and processes that generate and shape diversity in this arid mountain range. The geckos of the Ptyodactylus hasselquistii species complex are the largest geckos in Arabia and are found widely distributed across the Arabian Mountains, constituting a very important component of the reptile mountain fauna. Preliminary analyses suggested that their diversity in the Hajar Mountains may be higher than expected and that their systematics should be revised. In order to tackle these questions, we inferred a nearly complete calibrated phylogeny of the genus Ptyodactylus to identify the origin of the Hajar Mountains lineages using information from two mitochondrial and four nuclear genes. Genetic variability within the Hajar Mountains was further investigated using 68 specimens of Ptyodactylus from 46 localities distributed across the entire mountain range and sequenced for the same genes as above. The molecular phylogenies and morphological analyses as well as niche comparisons indicate the presence of two very old sister cryptic species living in allopatry: one restricted to the extreme northern Hajar Mountains and described as a new species herein; the other distributed across the rest of the Hajar Mountains that can be confidently assigned to the species P. orlovi. Similar to recent findings in the geckos of the genus Asaccus, the results of the present study uncover more hidden diversity in the northern Hajar Mountains and stress once again the importance of this unique mountain range as a hot spot of biodiversity and a priority focal point for reptile conservation in Arabia.

The Hidden Curriculum of Youth Policy: A Dutch Example

ERIC Educational Resources Information Center

Hopman, Marit; de Winter, Micha; Koops, Willem

2014-01-01

Youth policy is more than a mere response to the actual behavior of children, but it is equally influenced by values and beliefs of policy makers. These values are however rarely made explicit and, therefore, the authors refer to them as "the hidden curriculum" of youth policy. The study investigation explicates this hidden curriculum by…

Hidden School Dropout among Immigrant Students: A Cross-Sectional Study

ERIC Educational Resources Information Center

Makarova, Elena; Herzog, Walter

2013-01-01

Actual school dropout among immigrant youth has been addressed in a number of studies, but research on hidden school dropout among immigrant students is rare. Thus, the objective of this paper is to analyze hidden school dropout among primary school students with an immigrant background. The analyses were performed using survey data of 1186…

Secret Codes: The Hidden Curriculum of Semantic Web Technologies

ERIC Educational Resources Information Center

Edwards, Richard; Carmichael, Patrick

2012-01-01

There is a long tradition in education of examination of the hidden curriculum, those elements which are implicit or tacit to the formal goals of education. This article draws upon that tradition to open up for investigation the hidden curriculum and assumptions about students and knowledge that are embedded in the coding undertaken to facilitate…

Hidden Costs of Hospital Based Delivery from Two Tertiary Hospitals in Western Nepal.

PubMed

Acharya, Jeevan; Kaehler, Nils; Marahatta, Sujan Babu; Mishra, Shiva Raj; Subedi, Sudarshan; Adhikari, Bipin

2016-01-01

Hospital based delivery has been an expensive experience for poor households because of hidden costs which are usually unaccounted in hospital costs. The main aim of this study was to estimate the hidden costs of hospital based delivery and determine the factors associated with the hidden costs. A hospital based cross-sectional study was conducted among 384 post-partum mothers with their husbands/house heads during the discharge time in Manipal Teaching Hospital and Western Regional Hospital, Pokhara, Nepal. A face to face interview with each respondent was conducted using a structured questionnaire. Hidden costs were calculated based on the price rate of the market during the time of the study. The total hidden costs for normal delivery and C-section delivery were 243.4 USD (US Dollar) and 321.6 USD respectively. Of the total maternity care expenditures; higher mean expenditures were found for food & drinking (53.07%), clothes (9.8%) and transport (7.3%). For postpartum women with their husband or house head, the total mean opportunity cost of "days of work loss" were 84.1 USD and 81.9 USD for normal delivery and C-section respectively. Factors such as literate mother (p = 0.007), employed house head (p = 0.011), monthly family income more than 25,000 NRs (Nepalese Rupees) (p = 0.014), private hospital as a place of delivery (p = 0.0001), C-section as a mode of delivery (p = 0.0001), longer duration (>5days) of stay in hospital (p = 0.0001), longer distance (>15km) from house to hospital (p = 0.0001) and longer travel time (>240 minutes) from house to hospital (p = 0.007) showed a significant association with the higher hidden costs (>25000 NRs). Experiences of hidden costs on hospital based delivery and opportunity costs of days of work loss were found high. Several socio-demographic factors, delivery related factors (place and mode of delivery, length of stay, distance from hospital and travel time) were associated with hidden costs. Hidden costs can be a critical factor for many poor and remote households who attend the hospital for delivery. Current remuneration (10-15 USD for normal delivery, 30 USD for complicated delivery and 70 USD for caesarean section delivery) for maternity incentive needs to account the hidden costs by increasing it to 250 USD for normal delivery and 350 USD for C-section. Decentralization of the obstetric care to remote and under-privileged population might reduce the economic burden of pregnant women and can facilitate their attendance at the health care centers.

On the zigzagging causility model of EPR correlations and on the interpretation of quantum mechanics

NASA Astrophysics Data System (ADS)

de Beauregard, O. Costa

1988-09-01

Being formalized inside the S-matrix scheme, the zigzagging causility model of EPR correlations has full Lorentz and CPT invariance. EPR correlations, proper or reversed, and Wheeler's smoky dragon metaphor are respectively pictured in spacetime or in the momentum-energy space, as V-shaped, A-shaped, or C-shaped ABC zigzags, with a summation at B over virtual states |B>

Environmental triggers of Past Ebola Outbreaks in Africa, 1981 - 2014

NASA Astrophysics Data System (ADS)

Dartevelle, S.; NguyRobertson, A. L.

2016-12-01

Ebola virus, especially its most common and lethal form, Zaire Ebolavirus, has eluded scientists nearly 50 years. What is its primary host? Why does it go dormant to suddenly to reappear full force years later? What are the driving forces behind its intriguing dynamic? It has been surmised that local environmental factors (such as droughts, seasons) might be at play behind the on-and-off Ebola outbreak outbursts. However, so far, no clear lead has been demonstrated making Ebola a constant hidden lethal menace lurking in the environment for many African communities. We have analyzed long-term time-series of three environmental variables that influence the controlling factor behind the cycle of Ebola virus outbreaks: (i) vegetation health, as determined from the Normalized Difference Vegetation Index (NDVI) collected by AVHRR and MODIS satellite sensors, and the weather variables (ii) temperature and (iii) precipitation from the Climate Forecast System ver. 2. Time series data were averaged monthly and spatially over a 100 km grid around past known outbreak locations. Seasonal effects were removed from these time series before applying statistical analyses identifying causal linkages between NDVI, temperature, precipitation and Ebola outbreaks. Likewise, possible tipping-points prior to outbreaks (i.e., early warning signals of an upcoming outbreak) were identified. Our results indicate that there is a causal dynamic link between outbreaks and the three environmental variables examined months prior to an outbreak. This was likely due to an abnormal change in the local precipitation pattern which influence NDVI values and to a lesser extent temperature. Furthermore, our results provide evidence that these factors demonstrate early warning signals of a dynamical system at a tipping-point, prior to a future outbreak. These tipping-point or early warning models may open new ways to furthermore develop forecast models of future Ebola outbreaks. [US Government — Approved for Public Release 16-560].

Dopamine reward prediction errors reflect hidden state inference across time

PubMed Central

Starkweather, Clara Kwon; Babayan, Benedicte M.; Uchida, Naoshige; Gershman, Samuel J.

2017-01-01

Midbrain dopamine neurons signal reward prediction error (RPE), or actual minus expected reward. The temporal difference (TD) learning model has been a cornerstone in understanding how dopamine RPEs could drive associative learning. Classically, TD learning imparts value to features that serially track elapsed time relative to observable stimuli. In the real world, however, sensory stimuli provide ambiguous information about the hidden state of the environment, leading to the proposal that TD learning might instead compute a value signal based on an inferred distribution of hidden states (a ‘belief state’). In this work, we asked whether dopaminergic signaling supports a TD learning framework that operates over hidden states. We found that dopamine signaling exhibited a striking difference between two tasks that differed only with respect to whether reward was delivered deterministically. Our results favor an associative learning rule that combines cached values with hidden state inference. PMID:28263301

Modelling proteins' hidden conformations to predict antibiotic resistance

NASA Astrophysics Data System (ADS)

Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

2016-10-01

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM's specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models' prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.

Cosmological abundance of the QCD axion coupled to hidden photons

NASA Astrophysics Data System (ADS)

Kitajima, Naoya; Sekiguchi, Toyokazu; Takahashi, Fuminobu

2018-06-01

We study the cosmological evolution of the QCD axion coupled to hidden photons. For a moderately strong coupling, the motion of the axion field leads to an explosive production of hidden photons by tachyonic instability. We use lattice simulations to evaluate the cosmological abundance of the QCD axion. In doing so, we incorporate the backreaction of the produced hidden photons on the axion dynamics, which becomes significant in the non-linear regime. We find that the axion abundance is suppressed by at most O (102) for the decay constant fa =1016GeV, compared to the case without the coupling. For a sufficiently large coupling, the motion of the QCD axion becomes strongly damped, and as a result, the axion abundance is enhanced. Our results show that the cosmological upper bound on the axion decay constant can be relaxed by a few hundred for a certain range of the coupling to hidden photons.

Perspective: Disclosing hidden sources of funding.

PubMed

Resnik, David B

2009-09-01

In this article, the author discusses ethical and policy issues related to the disclosure of hidden sources of funding in research. The author argues that authors have an ethical obligation to disclose hidden sources of funding and that journals should adopt policies to enforce this obligation. Journal policies should require disclosure of hidden sources of funding that authors know about and that have a direct relation to their research. To stimulate this discussion, the author describes a recent case: investigators who conducted a lung cancer screening study had received funding from a private foundation that was supported by a tobacco company, but they did not disclose this relationship to the journal. Investigators and journal editors must be prepared to deal with these issues in a manner that promotes honesty, transparency, fairness, and accountability in research. The development of well-defined, reasonable policies pertaining to hidden sources of funding can be a step in this direction.

Modelling proteins’ hidden conformations to predict antibiotic resistance

PubMed Central

Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

2016-01-01

TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM’s specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models’ prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design. PMID:27708258

Dopamine reward prediction errors reflect hidden-state inference across time.

PubMed

Starkweather, Clara Kwon; Babayan, Benedicte M; Uchida, Naoshige; Gershman, Samuel J

2017-04-01

Midbrain dopamine neurons signal reward prediction error (RPE), or actual minus expected reward. The temporal difference (TD) learning model has been a cornerstone in understanding how dopamine RPEs could drive associative learning. Classically, TD learning imparts value to features that serially track elapsed time relative to observable stimuli. In the real world, however, sensory stimuli provide ambiguous information about the hidden state of the environment, leading to the proposal that TD learning might instead compute a value signal based on an inferred distribution of hidden states (a 'belief state'). Here we asked whether dopaminergic signaling supports a TD learning framework that operates over hidden states. We found that dopamine signaling showed a notable difference between two tasks that differed only with respect to whether reward was delivered in a deterministic manner. Our results favor an associative learning rule that combines cached values with hidden-state inference.

Identification of new risk factors for rolandic epilepsy: CNV at Xp22.31 and alterations at cholinergic synapses.

PubMed

Addis, Laura; Sproviero, William; Thomas, Sanjeev V; Caraballo, Roberto H; Newhouse, Stephen J; Gomez, Kumudini; Hughes, Elaine; Kinali, Maria; McCormick, David; Hannan, Siobhan; Cossu, Silvia; Taylor, Jacqueline; Akman, Cigdem I; Wolf, Steven M; Mandelbaum, David E; Gupta, Rajesh; van der Spek, Rick A; Pruna, Dario; Pal, Deb K

2018-05-22

Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in GRIN2A accounting for >5% of cases. To identify rare, causal CNV in patients with RE. We used high-density SNP arrays to analyse the presence of rare CNVs in 186 patients with RE from the UK, the USA, Sardinia, Argentina and Kerala, India. We identified 84 patients with one or more rare CNVs, and, within this group, 14 (7.5%) with recurrent risk factor CNVs and 15 (8.0%) with likely pathogenic CNVs. Nine patients carried recurrent hotspot CNVs including at 16p13.11 and 1p36, with the most striking finding that four individuals (three from Sardinia) carried a duplication, and one a deletion, at Xp22.31. Five patients with RE carried a rare CNV that disrupted genes associated with other epilepsies ( KCTD7 , ARHGEF15 , CACNA2D1, GRIN2A and ARHGEF4 ), and 17 cases carried CNVs that disrupted genes associated with other neurological conditions or that are involved in neuronal signalling/development. Network analysis of disrupted genes with high brain expression identified significant enrichment in pathways of the cholinergic synapse, guanine-exchange factor activation and the mammalian target of rapamycin. Our results provide a CNV profile of an ethnically diverse cohort of patients with RE, uncovering new areas of research focus, and emphasise the importance of studying non-western European populations in oligogenic disorders to uncover a full picture of risk variation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Nurture Hidden Talents: Transform School Culture into One That Values Teacher Expertise

ERIC Educational Resources Information Center

Zimmerman, Diane P.

2014-01-01

This article looks into the school culture where teacher expertise is often hidden and underused. While the media-rich culture places a high value on talent, the irony is that talent is underrated in most schools, and educators often remain silent about their hidden talents. Many school cultures are not conducive to dialogue that supports displays…

Nonparametric model validations for hidden Markov models with applications in financial econometrics

PubMed Central

Zhao, Zhibiao

2011-01-01

We address the nonparametric model validation problem for hidden Markov models with partially observable variables and hidden states. We achieve this goal by constructing a nonparametric simultaneous confidence envelope for transition density function of the observable variables and checking whether the parametric density estimate is contained within such an envelope. Our specification test procedure is motivated by a functional connection between the transition density of the observable variables and the Markov transition kernel of the hidden states. Our approach is applicable for continuous time diffusion models, stochastic volatility models, nonlinear time series models, and models with market microstructure noise. PMID:21750601

Hidden Area and Mechanical Nonlinearities in Freestanding Graphene.

PubMed

Nicholl, Ryan J T; Lavrik, Nickolay V; Vlassiouk, Ivan; Srijanto, Bernadeta R; Bolotin, Kirill I

2017-06-30

We investigated the effect of out-of-plane crumpling on the mechanical response of graphene membranes. In our experiments, stress was applied to graphene membranes using pressurized gas while the strain state was monitored through two complementary techniques: interferometric profilometry and Raman spectroscopy. By comparing the data obtained through these two techniques, we determined the geometric hidden area which quantifies the crumpling strength. While the devices with hidden area ∼0% obeyed linear mechanics with biaxial stiffness 428±10  N/m, specimens with hidden area in the range 0.5%-1.0% were found to obey an anomalous nonlinear Hooke's law with an exponent ∼0.1.

Hidden Area and Mechanical Nonlinearities in Freestanding Graphene

NASA Astrophysics Data System (ADS)

Nicholl, Ryan J. T.; Lavrik, Nickolay V.; Vlassiouk, Ivan; Srijanto, Bernadeta R.; Bolotin, Kirill I.

2017-06-01

We investigated the effect of out-of-plane crumpling on the mechanical response of graphene membranes. In our experiments, stress was applied to graphene membranes using pressurized gas while the strain state was monitored through two complementary techniques: interferometric profilometry and Raman spectroscopy. By comparing the data obtained through these two techniques, we determined the geometric hidden area which quantifies the crumpling strength. While the devices with hidden area ˜0 % obeyed linear mechanics with biaxial stiffness 428 ±10 N /m , specimens with hidden area in the range 0.5%-1.0% were found to obey an anomalous nonlinear Hooke's law with an exponent ˜0.1 .

Multilayer neural networks with extensively many hidden units.

PubMed

Rosen-Zvi, M; Engel, A; Kanter, I

2001-08-13

The information processing abilities of a multilayer neural network with a number of hidden units scaling as the input dimension are studied using statistical mechanics methods. The mapping from the input layer to the hidden units is performed by general symmetric Boolean functions, whereas the hidden layer is connected to the output by either discrete or continuous couplings. Introducing an overlap in the space of Boolean functions as order parameter, the storage capacity is found to scale with the logarithm of the number of implementable Boolean functions. The generalization behavior is smooth for continuous couplings and shows a discontinuous transition to perfect generalization for discrete ones.

Hidden hyperchaos and electronic circuit application in a 5D self-exciting homopolar disc dynamo

NASA Astrophysics Data System (ADS)

Wei, Zhouchao; Moroz, Irene; Sprott, J. C.; Akgul, Akif; Zhang, Wei

2017-03-01

We report on the finding of hidden hyperchaos in a 5D extension to a known 3D self-exciting homopolar disc dynamo. The hidden hyperchaos is identified through three positive Lyapunov exponents under the condition that the proposed model has just two stable equilibrium states in certain regions of parameter space. The new 5D hyperchaotic self-exciting homopolar disc dynamo has multiple attractors including point attractors, limit cycles, quasi-periodic dynamics, hidden chaos or hyperchaos, as well as coexisting attractors. We use numerical integrations to create the phase plane trajectories, produce bifurcation diagram, and compute Lyapunov exponents to verify the hidden attractors. Because no unstable equilibria exist in two parameter regions, the system has a multistability and six kinds of complex dynamic behaviors. To the best of our knowledge, this feature has not been previously reported in any other high-dimensional system. Moreover, the 5D hyperchaotic system has been simulated using a specially designed electronic circuit and viewed on an oscilloscope, thereby confirming the results of the numerical integrations. Both Matlab and the oscilloscope outputs produce similar phase portraits. Such implementations in real time represent a new type of hidden attractor with important consequences for engineering applications.

Hidden hyperchaos and electronic circuit application in a 5D self-exciting homopolar disc dynamo.

PubMed

Wei, Zhouchao; Moroz, Irene; Sprott, J C; Akgul, Akif; Zhang, Wei

2017-03-01

We report on the finding of hidden hyperchaos in a 5D extension to a known 3D self-exciting homopolar disc dynamo. The hidden hyperchaos is identified through three positive Lyapunov exponents under the condition that the proposed model has just two stable equilibrium states in certain regions of parameter space. The new 5D hyperchaotic self-exciting homopolar disc dynamo has multiple attractors including point attractors, limit cycles, quasi-periodic dynamics, hidden chaos or hyperchaos, as well as coexisting attractors. We use numerical integrations to create the phase plane trajectories, produce bifurcation diagram, and compute Lyapunov exponents to verify the hidden attractors. Because no unstable equilibria exist in two parameter regions, the system has a multistability and six kinds of complex dynamic behaviors. To the best of our knowledge, this feature has not been previously reported in any other high-dimensional system. Moreover, the 5D hyperchaotic system has been simulated using a specially designed electronic circuit and viewed on an oscilloscope, thereby confirming the results of the numerical integrations. Both Matlab and the oscilloscope outputs produce similar phase portraits. Such implementations in real time represent a new type of hidden attractor with important consequences for engineering applications.

Partially covered metal stents have longer patency than uncovered and fully covered metal stents in the management of distal malignant biliary obstruction: a retrospective study.

PubMed

Yokota, Yudai; Fukasawa, Mitsuharu; Takano, Shinichi; Kadokura, Makoto; Shindo, Hiroko; Takahashi, Ei; Hirose, Sumio; Kawakami, Satoshi; Fukasawa, Yoshimitsu; Sato, Tadashi; Enomoto, Nobuyuki

2017-10-11

Self-expandable metal stents (SEMSs) are widely used for malignant biliary obstructions. Nitinol-covered SEMSs have been developed to improve stent patency. Currently, SEMSs may be uncovered, partially covered, or fully covered; however, there is no consensus on the best stent type for the management of malignant distal biliary obstruction (MDBO). Patients with unresectable MDBO receiving SEMS (Wallflex™) were retrospectively analyzed. Time to recurrent biliary obstruction (TRBO) and survival time were compared among the three types of SEMSs. Univariate and multivariate analyses were performed to identify risk factors for stent dysfunction. In total, 101 patients received SEMSs for unresectable MDBO (44 uncovered, 28 partially covered, and 29 fully covered SEMSs). Median survival time was 200, 168, and 276 days in the uncovered, partially covered, and fully covered SEMSs groups, respectively. There were no differences in survival among the three groups. Median TRBO was 199, 444, and 194 days in the uncovered, partially covered, and fully covered SEMSs groups, respectively. Partially covered SEMSs had longer TRBO than uncovered (p = 0.013) and fully covered (p = 0.010) SEMSs. Tumor ingrowth occurred only with uncovered SEMSs and stent migration occurred only with fully covered SEMSs. Multivariate analyses confirmed that partially covered SEMSs have lower risk of dysfunction. Partially covered SEMSs with a proximal uncovered flared end have longer patency than uncovered and fully covered SEMSs by preventing tumor ingrowth and stent migration.

Causal Networks or Causal Islands? The Representation of Mechanisms and the Transitivity of Causal Judgment

ERIC Educational Resources Information Center

Johnson, Samuel G. B.; Ahn, Woo-kyoung

2015-01-01

Knowledge of mechanisms is critical for causal reasoning. We contrasted two possible organizations of causal knowledge--an interconnected causal "network," where events are causally connected without any boundaries delineating discrete mechanisms; or a set of disparate mechanisms--causal "islands"--such that events in different…

Humanism, the Hidden Curriculum, and Educational Reform: A Scoping Review and Thematic Analysis.

PubMed

Martimianakis, Maria Athina Tina; Michalec, Barret; Lam, Justin; Cartmill, Carrie; Taylor, Janelle S; Hafferty, Frederic W

2015-11-01

Medical educators have used the hidden curriculum concept for over three decades to make visible the effects of tacit learning, including how culture, structures, and institutions influence professional identity formation. In response to calls to see more humanistic-oriented training in medicine, the authors examined how the hidden curriculum construct has been applied in the English language medical education literature with a particular (and centering) look at its use within literature pertaining to humanism. They also explored the ends to which the hidden curriculum construct has been used in educational reform efforts (at the individual, organizational, and/or systems levels) related to nurturing and/or increasing humanism in health care. The authors conducted a scoping review and thematic analysis that draws from the tradition of critical discourse analysis. They identified 1,887 texts in the literature search, of which 200 met inclusion criteria. The analysis documents a strong preoccupation with negative effects of the hidden curriculum, particularly the moral erosion of physicians and the perceived undermining of humanistic values in health care. A conflation between professionalism and humanism was noted. Proposals for reform largely target medical students and medical school faculty, with very little consideration for how organizations, institutions, and sociopolitical relations more broadly contribute to problematic behaviors. The authors argue that there is a need to transcend conceptualizations of the hidden curriculum as antithetical to humanism and offer suggestions for future research that explores the necessity and value of humanism and the hidden curriculum in medical education and training.

The Matchmaker Exchange: a platform for rare disease gene discovery.

PubMed

Philippakis, Anthony A; Azzariti, Danielle R; Beltran, Sergi; Brookes, Anthony J; Brownstein, Catherine A; Brudno, Michael; Brunner, Han G; Buske, Orion J; Carey, Knox; Doll, Cassie; Dumitriu, Sergiu; Dyke, Stephanie O M; den Dunnen, Johan T; Firth, Helen V; Gibbs, Richard A; Girdea, Marta; Gonzalez, Michael; Haendel, Melissa A; Hamosh, Ada; Holm, Ingrid A; Huang, Lijia; Hurles, Matthew E; Hutton, Ben; Krier, Joel B; Misyura, Andriy; Mungall, Christopher J; Paschall, Justin; Paten, Benedict; Robinson, Peter N; Schiettecatte, François; Sobreira, Nara L; Swaminathan, Ganesh J; Taschner, Peter E; Terry, Sharon F; Washington, Nicole L; Züchner, Stephan; Boycott, Kym M; Rehm, Heidi L

2015-10-01

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow. © 2015 WILEY PERIODICALS, INC.

Towards large-cohort comparative studies to define the factors influencing the gut microbial community structure of ASD patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Daniel; Hornig, Mady; Lozupone, Catherine

Differences in the gut microbiota have been reported between individuals with autism spectrum disorders (ASD) and neurotypical controls, although direct evidence that changes in the microbiome contribute to causing ASD has been scarce to date. Here we summarize some considerations of experimental design that can help untangle causality in this complex system. In particular, large cross-sectional studies that can factor out important variables such as diet, prospective longitudinal studies that remove some of the influence of interpersonal variation in the microbiome (which is generally high, especially in children), and studies transferring microbial communities into germ-free mice may be especially useful.more » Controlling for the effects of technical variables, which have complicated efforts to combine existing studies, is critical when biological effect sizes are small. Large citizen-science studies with thousands of participants such as the American Gut Project have been effective at uncovering subtle microbiome effects in self-collected samples and with self-reported diet and behavior data, and may provide a useful complement to other types of traditionally funded and conducted studies in the case of ASD, especially in the hypothesis generation phase.« less

The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery

PubMed Central

Philippakis, Anthony A.; Azzariti, Danielle R.; Beltran, Sergi; Brookes, Anthony J.; Brownstein, Catherine A.; Brudno, Michael; Brunner, Han G.; Buske, Orion J.; Carey, Knox; Doll, Cassie; Dumitriu, Sergiu; Dyke, Stephanie O.M.; den Dunnen, Johan T.; Firth, Helen V.; Gibbs, Richard A.; Girdea, Marta; Gonzalez, Michael; Haendel, Melissa A.; Hamosh, Ada; Holm, Ingrid A.; Huang, Lijia; Hurles, Matthew E.; Hutton, Ben; Krier, Joel B.; Misyura, Andriy; Mungall, Christopher J.; Paschall, Justin; Paten, Benedict; Robinson, Peter N.; Schiettecatte, François; Sobreira, Nara L.; Swaminathan, Ganesh J.; Taschner, Peter E.; Terry, Sharon F.; Washington, Nicole L.; Züchner, Stephan; Boycott, Kym M.; Rehm, Heidi L.

2015-01-01

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for “the needle in a haystack” to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can “match” these cases to build evidence for causality. However, serendipity has never proven to be a reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. Three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow. PMID:26295439

TMS uncovers details about sub-regional language-specific processing networks in early bilinguals.

PubMed

Hämäläinen, Sini; Mäkelä, Niko; Sairanen, Viljami; Lehtonen, Minna; Kujala, Teija; Leminen, Alina

2018-05-01

Despite numerous functional neuroimaging and intraoperative electrical cortical mapping studies aimed at investigating the cortical organisation of native (L1) and second (L2) language processing, the neural underpinnings of bilingualism remain elusive. We investigated whether the neural network engaged in speech production over the bilateral posterior inferior frontal gyrus (pIFG) is the same (i.e., shared) or different (i.e., language-specific) for the two languages of bilingual speakers. Navigated transcranial magnetic stimulation (TMS) was applied over the left and right posterior inferior gyrus (pIFG), while early simultaneous bilinguals performed a picture naming task with their native languages. An ex-Gaussian distribution was fitted to the naming latencies and the resulting parameters were compared between languages and across stimulation conditions. The results showed that although the naming performance in general was highly comparable between the languages, TMS produced a language-specific effect when the pulses were delivered to the left pIFG at 200 ms poststimulus. We argue that this result causally demonstrates, for the first time, that even within common language-processing areas, there are distinct language-specific neural populations for the different languages in early simultaneous bilinguals. Copyright © 2018 Elsevier Inc. All rights reserved.

Association analysis of multiple traits by an approach of combining P values.

PubMed

Chen, Lili; Wang, Yong; Zhou, Yajing

2018-03-01

Increasing evidence shows that one variant can affect multiple traits, which is a widespread phenomenon in complex diseases. Joint analysis of multiple traits can increase statistical power of association analysis and uncover the underlying genetic mechanism. Although there are many statistical methods to analyse multiple traits, most of these methods are usually suitable for detecting common variants associated with multiple traits. However, because of low minor allele frequency of rare variant, these methods are not optimal for rare variant association analysis. In this paper, we extend an adaptive combination of P values method (termed ADA) for single trait to test association between multiple traits and rare variants in the given region. For a given region, we use reverse regression model to test each rare variant associated with multiple traits and obtain the P value of single-variant test. Further, we take the weighted combination of these P values as the test statistic. Extensive simulation studies show that our approach is more powerful than several other comparison methods in most cases and is robust to the inclusion of a high proportion of neutral variants and the different directions of effects of causal variants.

Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci

PubMed Central

Huang, Hailiang; Menelaou, Androniki; Redler, Silke; Becker, Tim; Heilmann, Stefanie; Yamany, Tarek; Duvic, Madeliene; Hordinsky, Maria; Norris, David; Price, Vera H.; Mackay-Wiggan, Julian; de Jong, Annemieke; DeStefano, Gina M.; Moebus, Susanne; Böhm, Markus; Blume-Peytavi, Ulrike; Wolff, Hans; Lutz, Gerhard; Kruse, Roland; Bian, Li; Amos, Christopher I.; Lee, Annette; Gregersen, Peter K.; Blaumeiser, Bettina; Altshuler, David; Clynes, Raphael; de Bakker, Paul I. W.; Nöthen, Markus M.; Daly, Mark J.; Christiano, Angela M.

2015-01-01

Alopecia areata (AA) is a prevalent autoimmune disease with ten known susceptibility loci. Here we perform the first meta-analysis in AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the MHC, where we fine-map 4 independent effects, all implicating HLA-DR as a key etiologic driver. Outside the MHC, we identify two novel loci that exceed statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, TGFß/Tregs and JAK kinase signaling, and support the causal role of aberrant immune processes in AA. PMID:25608926

The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery

DOE PAGES

Philippakis, Anthony A.; Azzariti, Danielle R.; Beltran, Sergi; ...

2015-09-17

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be amore » reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. In conclusion, three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow.« less

The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Philippakis, Anthony A.; Azzariti, Danielle R.; Beltran, Sergi

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for "the needle in a haystack" to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can "match" these cases to build evidence for causality. However, serendipity has never proven to be amore » reliable or scalable approach in science. As such, the Matchmaker Exchange (MME) was launched to provide a robust and systematic approach to rare disease gene discovery through the creation of a federated network connecting databases of genotypes and rare phenotypes using a common application programming interface (API). The core building blocks of the MME have been defined and assembled. In conclusion, three MME services have now been connected through the API and are available for community use. Additional databases that support internal matching are anticipated to join the MME network as it continues to grow.« less

Does Hunger Contribute to Socioeconomic Gradients in Behavior?

PubMed Central

Nettle, Daniel

2017-01-01

Recent research has uncovered many examples of socioeconomic gradients in behavior and psychological states. As yet there is no theoretical consensus on the nature of the causal processes that produce these gradients. Here, I present the hunger hypothesis, namely the claim that part of the reason that people of lower socioeconomic position behave and feel as they do is that they are relatively often hungry. The hunger hypothesis applies in particular to impulsivity-hyperactivity, irritability-aggression, anxiety, and persistent narcotic use, all of which have been found to show socioeconomic gradients. I review multiple lines of evidence showing that hunger produces strong increases in these outcomes. I also review the literatures on food insufficiency and food insecurity to show that, within affluent societies, the poor experience a substantial burden of hunger, despite obtaining sufficient or excess calories on average. This leads to the distinctive prediction that hunger is an important mediator of the relationships between socioeconomic variables and the behavioral/psychological outcomes. This approach has a number of far-reaching implications, not least that some behavioral and psychological differences between social groups, though persistent under current economic arrangements, are potentially highly reversible with changes to the distribution of financial resources and food. PMID:28344567

Screen Media Exposure and Obesity in Children and Adolescents.

PubMed

Robinson, Thomas N; Banda, Jorge A; Hale, Lauren; Lu, Amy Shirong; Fleming-Milici, Frances; Calvert, Sandra L; Wartella, Ellen

2017-11-01

Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children's preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context. Copyright © 2017 by the American Academy of Pediatrics.

Experimental Myocardial Infarction Upregulates Circulating Fibroblast Growth Factor‐23

PubMed Central

Andrukhova, Olena; Slavic, Svetlana; Odörfer, Kathrin I; Erben, Reinhold G

2015-01-01

ABSTRACT Myocardial infarction (MI) is a major cause of death worldwide. Epidemiological studies have linked vitamin D deficiency to MI incidence. Because fibroblast growth factor‐23 (FGF23) is a master regulator of vitamin D hormone production and has been shown to be associated with cardiac hypertrophy per se, we explored the hypothesis that FGF23 may be a previously unrecognized pathophysiological factor causally linked to progression of cardiac dysfunction post‐MI. Here, we show that circulating intact Fgf23 was profoundly elevated, whereas serum vitamin D hormone levels were suppressed, after induction of experimental MI in rat and mouse models, independent of changes in serum soluble Klotho or serum parathyroid hormone. Both skeletal and cardiac expression of Fgf23 was increased after MI. Although the molecular link between the cardiac lesion and circulating Fgf23 concentrations remains to be identified, our study has uncovered a novel heart–bone–kidney axis that may have important clinical implications and may inaugurate the new field of cardio‐osteology. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). PMID:25858796

World views: Their nature and function in the biology classroom

NASA Astrophysics Data System (ADS)

Armstrong, Kerri Lynn

There has been sufficient research in the area of conceptual change that indicates that students' conceptions or alternative theories are much more resistant to change than was previously thought. The work of cultural anthropologists and, more recently science educators, points to the role of individual world views in the learning of science concepts. A world view is one's fundamental assumptions and presuppositions concerning perceptions of reality. The purpose of this ethnographic investigation was to shed light on the dynamic interaction of individual world views within the college biology classroom in relation to understanding key biological concepts in genetics, evolution and natural selection, and ecology and ecological relationships. The subjects for this study were 22 students enrolled in an introductory level non-majors biology class at the Community College of Philadelphia. Ten of these students participated in the interviews reported here. The outcomes of this investigation revealed that students do not view themselves as part of science or nature. The investigation also uncovered students' views of the self, nonself, relationship and causality that affect their learning and apprehension of key biological concepts. This investigation provides further demonstration of the influence of world views and the interplay of those views with the notion of scientific literacy.

Genetic Susceptibility to ANCA-Associated Vasculitis: State of the Art

PubMed Central

Bonatti, Francesco; Reina, Michele; Neri, Tauro Maria; Martorana, Davide

2014-01-01

ANCA-associated vasculitis (AAV) is a group of disorders that is caused by inflammation affecting small blood vessels. Both arteries and veins are affected. AAV includes microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) renamed from Wegener’s granulomatosis, and eosinophilic granulomatosis with polyangiitis (EGPA), renamed from Churg–Strauss syndrome. AAV is primarily due to leukocyte migration and resultant damage. Despite decades of research, the mechanisms behind AAV disease etiology are still not fully understood, although it is clear that genetic and environmental factors are involved. To improve the understanding of the disease, the genetic component has been extensively studied by candidate association studies and two genome-wide association studies. The majority of the identified genetic AAV risk factors are common variants. These have uncovered information that still needs further investigation to clarify its importance. In this review, we summarize and discuss the results of the genetic studies in AAV. We also present the novel approaches to identifying the causal variants in complex susceptibility loci and disease mechanisms. Finally, we discuss the limitations of current methods and the challenges that we still have to face in order to incorporate genomic and epigenomic data into clinical practice. PMID:25452756

A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.

PubMed

Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N

2016-04-01

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

PubMed

Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

2016-05-01

Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Towards large-cohort comparative studies to define the factors influencing the gut microbial community structure of ASD patients

DOE PAGES

McDonald, Daniel; Hornig, Mady; Lozupone, Catherine; ...

2015-03-09

Differences in the gut microbiota have been reported between individuals with autism spectrum disorders (ASD) and neurotypical controls, although direct evidence that changes in the microbiome contribute to causing ASD has been scarce to date. Here we summarize some considerations of experimental design that can help untangle causality in this complex system. In particular, large cross-sectional studies that can factor out important variables such as diet, prospective longitudinal studies that remove some of the influence of interpersonal variation in the microbiome (which is generally high, especially in children), and studies transferring microbial communities into germ-free mice may be especially useful.more » Controlling for the effects of technical variables, which have complicated efforts to combine existing studies, is critical when biological effect sizes are small. Large citizen-science studies with thousands of participants such as the American Gut Project have been effective at uncovering subtle microbiome effects in self-collected samples and with self-reported diet and behavior data, and may provide a useful complement to other types of traditionally funded and conducted studies in the case of ASD, especially in the hypothesis generation phase.« less

Behavioral and Temporal Pattern Detection Within Financial Data With Hidden Information

DTIC Science & Technology

2012-02-01

probabilistic pattern detector to monitor the pattern. 15. SUBJECT TERMS Runtime verification, Hidden data, Hidden Markov models, Formal specifications...sequences in many other fields besides financial systems [L, TV, LC, LZ ]. Rather, the technique suggested in this paper is positioned as a hybrid...operation of the pattern detector . Section 7 describes the operation of the probabilistic pattern-matching monitor, and section 8 describes three

Image Steganography for Hidden Communication

DTIC Science & Technology

2000-04-01

ARMY RESEARCH LABORATORY Image Steganography for Hidden Communication by Lisa M. Marvel sx:8 lÄPSilll msmmmmsi IH :’:-:’X^:-:-:-:o-x...2000 Image Steganography for Hidden Communication Lisa M. Marvel Information Science and Technology Directorate, ARL Approved for public release...Capacity for Image Steganography 14 3.4 Summary 1’ 4. Spread Spectrum Image Steganography (SSIS) 19 4.1 Modulation 21 4.1.1 Sign-Detector System

2015 Cataloging Hidden Special Collections and Archives Unconference and Symposium: Innovation, Collaboration, and Models. Proceedings of the CLIR Cataloging Hidden Special Collections and Archives Symposium (Philadelphia, Pennsylvania, March 12-13, 2015)

ERIC Educational Resources Information Center

Oestreicher, Cheryl, Ed.

2015-01-01

The 2015 CLIR Unconference & Symposium was the capstone event to seven years of grant funding through CLIR's Cataloging Hidden Special Collections and Archives program. These proceedings group presentations by theme. Collaborations provides examples of multi-institutional projects, including one international collaboration; Student and Faculty…

Hidden Statistics of Schroedinger Equation

NASA Technical Reports Server (NTRS)

Zak, Michail

2011-01-01

Work was carried out in determination of the mathematical origin of randomness in quantum mechanics and creating a hidden statistics of Schr dinger equation; i.e., to expose the transitional stochastic process as a "bridge" to the quantum world. The governing equations of hidden statistics would preserve such properties of quantum physics as superposition, entanglement, and direct-product decomposability while allowing one to measure its state variables using classical methods.

The Hidden Messages of Secondary Reading Programs: What Students Learn vs. What Teachers Teach.

ERIC Educational Resources Information Center

Battraw, Judith L.

Hidden messages are part of the culture of reading at any school, particularly at the secondary level. In many schools, the overt message that reading is essential to success on state-mandated tests and in society is jeopardized due to hidden messages about the nature of the reading process and the place of reading in everyday life. A qualitative…