Sample records for development remains largely

  1. Ground-water hydraulics, regional flow, and ground-water development of the Floridan aquifer system in Florida and in parts of Georgia, South Carolina, and Alabama

    USGS Publications Warehouse

    Bush, Peter W.; Johnston, Richard H.

    1988-01-01

    A considerable area remains of the Floridan aquifer system where large ground-water supplies may be developed. This area is largely inland from the coasts and characterized by high transmissivity and minimal development prior to the early 1980's. The major constraint on future development probably is degradation of water quality rather than water-quantity limitations.

  2. Professional Development: Then and Now

    ERIC Educational Resources Information Center

    Bolt, Susan

    2012-01-01

    Technological developments have altered pedagogies in classroom teaching but approaches to teacher professional development have remained largely unchanged. The purpose of this paper is to describe an evolving learning process that spans the last decade and draws from three different investigations into professional development. The author…

  3. The Vital Program: Transforming ICT Professional Development

    ERIC Educational Resources Information Center

    Bradshaw, Pete; Twining, Peter; Walsh, Christopher S.

    2012-01-01

    Developing a model for effective large-scale continuous professional development (CPD) for teachers remains a significant obstacle for many governments worldwide. This article describes the development and evolution of Vital--a CPD program designed to enhance the teaching of information communication technology in state-funded primary and…

  4. Developing a "Semi-Systematic" Approach to Using Large-Scale Data-Sets for Small-Scale Interventions: The "Baby Matterz" Initiative as a Case Study

    ERIC Educational Resources Information Center

    O'Brien, Mark

    2011-01-01

    The appropriateness of using statistical data to inform the design of any given service development or initiative often depends upon judgements regarding scale. Large-scale data sets, perhaps national in scope, whilst potentially important in informing the design, implementation and roll-out of experimental initiatives, will often remain unused…

  5. An Impact Evaluation of the "FoodMate" Programme: Perspectives of Homeless Young People and Staff

    ERIC Educational Resources Information Center

    Meiklejohn, Sarah J.; Barbour, Liza; Palermo, Claire E.

    2017-01-01

    Objectives: Food insecurity remains an issue for vulnerable populations in developed countries. The potential dietary and food security impacts of nutrition education programmes in Australia remain largely undocumented. This study investigated the impacts of an eight-session nutrition education programme delivered within community case management…

  6. Medical tourism today: what is the state of existing knowledge?

    PubMed

    Hopkins, Laura; Labonté, Ronald; Runnels, Vivien; Packer, Corinne

    2010-07-01

    One manifestation of globalization is medical tourism. As its implications remain largely unknown, we reviewed claimed benefits and risks. Driven by high health-care costs, long waiting periods, or lack of access to new therapies in developed countries, most medical tourists (largely from the United States, Canada, and Western Europe) seek care in Asia and Latin America. Although individual patient risks may be offset by credentialing and sophistication in (some) destination country facilities, lack of benefits to poorer citizens in developing countries offering medical tourism remains a generic equity issue. Data collection, measures, and studies of medical tourism all need to be greatly improved if countries are to assess better both the magnitude and potential health implications of this trade.

  7. Large Eddy Simulations of Transverse Combustion Instability in a Multi-Element Injector

    DTIC Science & Technology

    2016-07-27

    plagued the development of liquid rocket engines and remains a large riskin the development and acquisition of new liquid rocket engines. Combustion...simulations to better understand the physics that can lead combustion instability in liquid rocket engines. Simulations of this type are able to...instabilities found in liquid rocket engines are transverse. The motivating of the experiment behind the current work is to subject the CVRC injector

  8. Childhood Rituals and Executive Functions

    ERIC Educational Resources Information Center

    Tregay, Jenifer; Gilmour, Jane; Charman, Tony

    2009-01-01

    Repetitive and ritualistic behaviours (RRBs) are a feature of both typical and atypical development. While the cognitive correlates of these behaviours have been investigated in some neurodevelopmental conditions these links remain largely unexplored in typical development. The current study examined the relationship between RRBs and executive…

  9. The Changing Landscape of Education in Africa: Quality, Equality and Democracy

    ERIC Educational Resources Information Center

    Johnson, David, Ed.

    2008-01-01

    It is 40 years since Coombs (1967) first drew attention to the World Education Crisis, and specifically problems in the educational systems of countries in the developing world. Today, many of these problems remain, and are most visible in the educational systems of countries in sub-Saharan Africa. A large number of children remain out of school…

  10. Appropedia as a Tool for Service Learning in Sustainable Development

    ERIC Educational Resources Information Center

    Pearce, Joshua M.

    2009-01-01

    Numerous studies have demonstrated that university students are capable of contributing to sustainable development while improving their academic skills. Unfortunately for many institutions, the expense of sending large cohorts of students on international service learning trips is prohibitive. Yet, students remain enthusiastic and well equipped…

  11. A National Perspective: An Analysis of Factors That Influence Special Educators to Remain in the Field of Education

    ERIC Educational Resources Information Center

    Nickson, Lautrice M.; Kritsonis, William Allan

    2006-01-01

    The purpose of this article is to analyze factors that influence special educators to remain in the field of education. School administrators are perplexed by the large number of teachers who decide to leave the field of education after three years. The retention rates of special educators' require school administrators to focus on developing a…

  12. Using Learning Trajectories for Teacher Learning to Structure Professional Development

    ERIC Educational Resources Information Center

    Bargagliotti, Anna E.; Anderson, Celia Rousseau

    2017-01-01

    As a result of the increased focus on data literacy and data science across the world, there has been a large demand for professional development in statistics. However, exactly how these professional development opportunities should be structured remains an open question. The purpose of this paper is to describe the first iteration of a design…

  13. The Development of Stranger Fear in Infancy and Toddlerhood: Normative Development, Individual Differences, Antecedents, and Outcomes

    ERIC Educational Resources Information Center

    Brooker, Rebecca J.; Buss, Kristin A.; Lemery-Chalfant, Kathryn; Aksan, Nazan; Davidson, Richard J.; Goldsmith, H. Hill

    2013-01-01

    Despite implications that stranger fear is an important aspect of developing behavioral inhibition, a known risk factor for anxiety, normative and atypical developmental trajectories of stranger fear across infancy and toddlerhood remain understudied. We used a large, longitudinal data set (N = 1285) including multi-trait, multi-method assessments…

  14. Vygotsky's Legacy: A Foundation for Research and Practice

    ERIC Educational Resources Information Center

    Gredler, Margaret E.; Shields, Carolyn Claytor

    2007-01-01

    Most educators are familiar with Lev Vygotsky's concept of the "zone of proximal development," yet the bulk of Vygotsky's pioneering theory of cognitive development largely remains unknown. This volume provides a systematic, authoritative overview of Vygotsky's work and its implications for educational research and practice. Major topics include…

  15. Childhood Giftedness, Adolescent Agency: A Systemic Multiple-Case Study

    ERIC Educational Resources Information Center

    Mudrak, Jiri; Zabrodska, Katerina

    2015-01-01

    Although considerable research has addressed development from childhood giftedness to adult excellence, subjective perceptions of this development by gifted individuals themselves have remained largely unexplored. This multiple case study examined the ways in which young adults, who in the past had been identified as gifted, made sense of their…

  16. An innovative computer design for modeling forest landscape change in very large spatial extents with fine resolutions

    Treesearch

    Jian Yang; Hong S. He; Stephen R. Shifley; Frank R. Thompson; Yangjian Zhang

    2011-01-01

    Although forest landscape models (FLMs) have benefited greatly from ongoing advances of computer technology and software engineering, computing capacity remains a bottleneck in the design and development of FLMs. Computer memory overhead and run time efficiency are primary limiting factors when applying forest landscape models to simulate large landscapes with fine...

  17. (New hosts and vectors for genome cloning)

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

    Not Available

    The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

  18. [New hosts and vectors for genome cloning]. Progress report

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

    Not Available

    The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

  19. One-to-One Pedagogy: Developing a Protocol for Illuminating the Nature of Teaching in the Conservatoire

    ERIC Educational Resources Information Center

    Carey, Gemma; Grant, Catherine; McWilliam, Erica; Taylor, Peter

    2013-01-01

    This article outlines the approach used to develop a scheme to characterize the nature and quality of specific practices of one-to-one teaching, selected on the basis of their potential significance to the development of student performance. Although the value of one-to-one teaching remains largely unchallenged at the conservatoire level, music…

  20. The Path to Development: Expatriate Faculty Retention in the UAE

    ERIC Educational Resources Information Center

    Schoepp, Kevin W.

    2011-01-01

    Given the rapid development and large expatriate majority within the United Arab Emirates, the country is extremely reliant upon expatriate faculty to educate its people. Through the lens provided by Social Exchange Theory, this study examined the motivations of expatriate faculty to remain or leave their positions at institutions within the UAE.…

  1. Testing Alternative Hypotheses Regarding the Association between Behavioral Inhibition and Language Development in Toddlerhood

    ERIC Educational Resources Information Center

    Watts, Ashley K. Smith; Patel, Deepika; Corley, Robin P.; Friedman, Naomi P.; Hewitt, John K.; Robinson, JoAnn L.; Rhee, Soo H.

    2014-01-01

    Studies have reported an inverse association between language development and behavioral inhibition or shyness across childhood, but the direction of this association remains unclear. This study tested alternative hypotheses regarding this association in a large sample of toddlers. Data on behavioral inhibition and expressive and receptive…

  2. How Teachers Become Leaders: An Internationally Validated Theoretical Model of Teacher Leadership Development

    ERIC Educational Resources Information Center

    Poekert, Philip; Alexandrou, Alex; Shannon, Darbianne

    2016-01-01

    Teacher leadership is increasingly being touted as a practical response to guide teacher learning in school improvement and policy reform efforts. However, the field of research on teacher leadership in relation to post-compulsory educational development has been and remains largely atheoretical to date. This empirical study proposes a grounded…

  3. What will the future of cloud-based astronomical data processing look like?

    NASA Astrophysics Data System (ADS)

    Green, Andrew W.; Mannering, Elizabeth; Harischandra, Lloyd; Vuong, Minh; O'Toole, Simon; Sealey, Katrina; Hopkins, Andrew M.

    2017-06-01

    Astronomy is rapidly approaching an impasse: very large datasets require remote or cloud-based parallel processing, yet many astronomers still try to download the data and develop serial code locally. Astronomers understand the need for change, but the hurdles remain high. We are developing a data archive designed from the ground up to simplify and encourage cloud-based parallel processing. While the volume of data we host remains modest by some standards, it is still large enough that download and processing times are measured in days and even weeks. We plan to implement a python based, notebook-like interface that automatically parallelises execution. Our goal is to provide an interface sufficiently familiar and user-friendly that it encourages the astronomer to run their analysis on our system in the cloud-astroinformatics as a service. We describe how our system addresses the approaching impasse in astronomy using the SAMI Galaxy Survey as an example.

  4. Salt-gradient Solar Ponds: Summary of US Department of Energy Sponsored Research

    NASA Technical Reports Server (NTRS)

    French, R. L.; Johnson, D. H.; Jones, G. F.; Zangrando, F.

    1984-01-01

    The solar pond research program conducted by the United States Department of Energy was discontinued after 1983. This document summarizes the results of the program, reviews the state of the art, and identifies the remaining outstanding issues. Solar ponds is a generic term but, in the context of this report, the term solar pond refers specifically to saltgradient solar pond. Several small research solar ponds have been built and successfully tested. Procedures for filling the pond, maintaining the gradient, adjusting the zone boundaries, and extracting heat were developed. Theories and models were developed and verified. The major remaining unknowns or issues involve the physical behavior of large ponds; i.e., wind mixing of the surface, lateral range or reach of horizontally injected fluids, ground thermal losses, and gradient zone boundary erosion caused by pumping fluid for heat extraction. These issues cannot be scaled and must be studied in a large outdoor solar pond.

  5. Paving the Road to Success: Reflecting Critically on Year One of an Undergraduate Student Support Programme at a Large South African University

    ERIC Educational Resources Information Center

    de Klerk, Danie; Spark, Linda; Jones, Andrew; Maleswena, Tshepiso

    2017-01-01

    Student success, faculty and university throughput, and the need for adequate and appropriate student support remain prevalent issues in the South African and global higher education sectors. Subsequently, the Faculty of Commerce, Law, and Management at a large South African university applied for Teaching and Development Grant funding in order to…

  6. MIADS2 ... an alphanumeric map information assembly and display system for a large computer

    Treesearch

    Elliot L. Amidon

    1966-01-01

    A major improvement and extension of the Map Information Assembly and Display System (MIADS) developed in 1964 is described. Basic principles remain unchanged, but the computer programs have been expanded and rewritten for a large computer, in Fortran IV and MAP languages. The code system is extended from 99 integers to about 2,200 alphanumeric 2-character codes. Hand-...

  7. Vaccinology in the third millennium: scientific and social challenges

    PubMed Central

    Poland, Gregory A.; Whitaker, Jennifer A.; Poland, Caroline M.; Ovsyannikova, Inna G.; Kennedy, Richard B.

    2016-01-01

    The epidemiology of deaths due to vaccine-preventable diseases has been significantly and positively altered through the use of vaccines. Despite this, significant challenges remain in vaccine development and use in the third millennium. Both new (Ebola, Chikungunya, West Nile) and re-emerging diseases (measles, mumps, influenza) require the development of new or next-generation vaccines. The global aging of the population, and accumulating numbers of immunocompromised persons, will require new vaccine and adjuvant development to protect large segments of the population. After vaccine development, significant challenges remain globally in the cost and efficient use and acceptance of vaccines by the public. This article raises issues in these two areas and suggests a way forward that will benefit current and future generations. PMID:27039875

  8. Primer on Condition Curves for Water Mains

    EPA Science Inventory

    ABSTRACT The development of economical tools to prioritize pipe renewal based upon structural condition and remaining asset life is essential to effectively manage water infrastructure assets for both large and small diameter pipes. One tool that may facilitate asset management...

  9. Case Studies in U.S. Distance Education: Implications for Ghana's Under-Served High Schools

    ERIC Educational Resources Information Center

    Nsiah, Gabriel Kofi Boahen

    2010-01-01

    Ghana, like many other nations in recent years, has made education a top priority for national development. Despite newly developed policies, however, there remains a significant quality gap among high schools; due largely to an inequitable ratio of government's educational spending by geographic area. While most urban schools flourish with better…

  10. Communicative and Linguistic Development in Preterm Children: A Longitudinal Study from 12 to 24 Months

    ERIC Educational Resources Information Center

    Cattani, Allegra; Bonifacio, Serena; Fertz, Mariacristina; Iverson, Jana M.; Zocconi, Elisabetta; Caselli, M. Cristina

    2010-01-01

    Background: Research conducted on preterm children's linguistic skills has provided varying pictures, and the question of whether and to what extent preterm children are delayed in early language acquisition remains largely unresolved. Aims: To examine communicative and linguistic development during the second year in a group of Italian children…

  11. Testing the Predictors of Boredom at School: Development and Validation of the Precursors to Boredom Scales

    ERIC Educational Resources Information Center

    Daschmann, Elena C.; Goetz, Thomas; Stupnisky, Robert H.

    2011-01-01

    Background: Boredom has been found to be an important emotion for students' learning processes and achievement outcomes; however, the precursors of this emotion remain largely unexplored. Aim: In the current study, scales assessing the precursors to boredom in academic achievement settings were developed and tested. Sample: Participants were 1,380…

  12. Relational Agency and Teacher Development: A CHAT Analysis of a Collaborative Professional Inquiry Project with Biology Teachers

    ERIC Educational Resources Information Center

    McNicholl, Jane

    2013-01-01

    Teacher quality largely determines student outcomes and many argue for high quality teacher training and professional development (PD). Much PD has been heavily critiqued and what constitutes effective provision for teachers remains contested. Disenfranchisement of teachers, through neglect of prior expertise and failure to acknowledge teachers'…

  13. [New hosts and vectors for genome cloning]. Progress report, 1990--1991

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

    Not Available

    The main goal of our project remains the development of new bacterial hosts and vectors for the stable propagation of human DNA clones in E. coli. During the past six months of our current budget period, we have (1) continued to develop new hosts that permit the stable maintenance of unstable features of human DNA, and (2) developed a series of vectors for (a) cloning large DNA inserts, (b) assessing the frequency of human sequences that are lethal to the growth of E. coli, and (c) assessing the stability of human sequences cloned in M13 for large-scale sequencing projects.

  14. Inference of Evolutionary Jumps in Large Phylogenies using Lévy Processes

    PubMed Central

    Duchen, Pablo; Leuenberger, Christoph; Szilágyi, Sándor M.; Harmon, Luke; Eastman, Jonathan; Schweizer, Manuel

    2017-01-01

    Abstract Although it is now widely accepted that the rate of phenotypic evolution may not necessarily be constant across large phylogenies, the frequency and phylogenetic position of periods of rapid evolution remain unclear. In his highly influential view of evolution, G. G. Simpson supposed that such evolutionary jumps occur when organisms transition into so-called new adaptive zones, for instance after dispersal into a new geographic area, after rapid climatic changes, or following the appearance of an evolutionary novelty. Only recently, large, accurate and well calibrated phylogenies have become available that allow testing this hypothesis directly, yet inferring evolutionary jumps remains computationally very challenging. Here, we develop a computationally highly efficient algorithm to accurately infer the rate and strength of evolutionary jumps as well as their phylogenetic location. Following previous work we model evolutionary jumps as a compound process, but introduce a novel approach to sample jump configurations that does not require matrix inversions and thus naturally scales to large trees. We then make use of this development to infer evolutionary jumps in Anolis lizards and Loriinii parrots where we find strong signal for such jumps at the basis of clades that transitioned into new adaptive zones, just as postulated by Simpson’s hypothesis. [evolutionary jump; Lévy process; phenotypic evolution; punctuated equilibrium; quantitative traits. PMID:28204787

  15. Adaptive Management of Social-Ecological Systems: The Path Forward

    EPA Science Inventory

    Adaptive management remains at the forefront of environmental management nearly 40 years after its original conception, largely because we have yet to develop other methodologies that offer the same promise. Despite the criticisms of adaptive management and the numerous failed at...

  16. Relations between Intuitive Biological Thinking and Biological Misconceptions in Biology Majors and Nonmajors

    ERIC Educational Resources Information Center

    Coley, John D.; Tanner, Kimberly

    2015-01-01

    Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed "misconceptions," among biology students across biological domains. In parallel, cognitive and developmental psychologists…

  17. A critical needs assessment for collaborative ecotourism development linked to protected areas in Cross River State, Nigeria

    Treesearch

    Jeffrey J. Brooks; John Neary; Blessing E. Asuquo

    2007-01-01

    Nigeria has abundant natural resources, and the nation, working with its partners over the years, has made large strides toward conservation of this natural wealth, but the future of Nigeria's natural resources remains uncertain.

  18. Transcriptional regulators transforming growth factor-beta 1 and estrogen-related receptor-alpha identified as putative mediators of calf rumen epithelial tissue development and function during weaning

    USDA-ARS?s Scientific Manuscript database

    Molecular mechanisms controlling rumen epithelial development at weaning remain largely unknown. To identify gene networks and regulatory factors responsive to concentrate versus forage feeding at weaning, Holstein bull calves (n = 18) were fed commercial milk replacer only (MRO) until 42 d of age. ...

  19. Reaching the Hard Places: A Three-Year Evaluation of the Addition of Concise Online E-Clips into an Academic Development Program

    ERIC Educational Resources Information Center

    Quinn, Diana

    2010-01-01

    Purpose: The purpose of this paper is to examine current approaches to teaching used in academic development services and consider the diversity of their learners (academic faculty). Faculty engagement with teaching issues and innovations remains a concern for the higher education sector. The academic population contains large numbers of…

  20. Inherited Disorders as a Risk Factor and Predictor of Neurodevelopmental Outcome in Pediatric Cancer

    ERIC Educational Resources Information Center

    Ullrich, Nicole J.

    2008-01-01

    Each year in the United States, an average of one to two children per 10,000 develop cancer. The etiology of most childhood cancer remains largely unknown but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition…

  1. Large protein as a potential target for use in rabies diagnostics.

    PubMed

    Santos Katz, I S; Dias, M H; Lima, I F; Chaves, L B; Ribeiro, O G; Scheffer, K C; Iwai, L K

    Rabies is a zoonotic viral disease that remains a serious threat to public health worldwide. The rabies lyssavirus (RABV) genome encodes five structural proteins, multifunctional and significant for pathogenicity. The large protein (L) presents well-conserved genomic regions, which may be a good alternative to generate informative datasets for development of new methods for rabies diagnosis. This paper describes the development of a technique for the identification of L protein in several RABV strains from different hosts, demonstrating that MS-based proteomics is a potential method for antigen identification and a good alternative for rabies diagnosis.

  2. Sapporo, Hokkaido, Japan

    NASA Image and Video Library

    1992-09-20

    The city of Sapporo on the northernmost of the Japanese Home Island of Hokkaido (43.5N, 141.5E), host to the 1986 Winter Olympic Games is situated along the margin of a large valley which extends across the island from the Sea of Japan to the Pacific Ocean. The Valley is largely cultivated (the lighter green of the cultivated land distinguishes it from the gray urban development of Sapporo), but much of the island remains heavily forested.

  3. Doctoral Student Learning and Development: A Shared Responsibility

    ERIC Educational Resources Information Center

    Bair, Carolyn R.; Haworth, Jennifer Grant; Sandfort, Melissa

    2004-01-01

    Historically, student affairs professionals focused their work almost exclusively on undergraduate students. Doctoral faculty remained focused on the comprehensive needs of doctoral students. However, this situation is changing. Due largely to growth in numbers and diversity of graduate students, student affairs professionals at colleges and…

  4. The Status of Contemporary Image-Guided Modalities in Oncologic Surgery

    PubMed Central

    Rosenthal, Eben L; Warram, Jason M; Bland, Kirby I; Zinn, Kurt R

    2014-01-01

    Surgical resection remains the cornerstone of therapy for patients with early stage solid malignancies and more than half of all cancer patients undergo surgery each year. The technical ability of the surgeon to obtain clear surgical margins at the initial resection remains crucial to improve overall survival and long-term morbidity. Current resection techniques are largely based on subjective and subtle changes associated with tissue distortion by invasive cancer. As a result, positive surgical margins occur in a significant portion of tumor resections, which is directly correlated with a poor outcome. A variety of cancer imaging techniques have been adapted or developed for intraoperative surgical guidance that have been shown to improve functional and oncologic outcomes in randomized clinical trials. There are also a large number of novel, cancer-specific contrast agents that are in early stage clinical trials and preclinical development that demonstrate significant promise to improve real-time detection of subclinical cancer in the operative setting. PMID:25599326

  5. A Framework for Sustainable Energy Development beyond the Grid: Meeting the Needs of Rural and Remote Populations

    ERIC Educational Resources Information Center

    Agbemabiese, Lawrence

    2009-01-01

    Advances in energy access in developing countries over the past 25 years have been remarkable with more than 1 billion unserved people gaining access to electricity and modern fuels. However, as impressive as this may sound, large gaps remain: 1.6 billion people still lack access to electricity and another 2.5 billion continue to rely on…

  6. INTEGRATED WASTE AND WATER MANAGEMENT PROJECT (IWWMP) – BATANGAS, PHILIPPINES

    EPA Science Inventory

    Mass evacuations of rural residents in the Philippines to large urban areas overburden an already strained infrastructure. There have been investments by non-profit groups to develop housing to attract the evacuees back to their regions. However, there remains a great need for...

  7. Developing new minds

    NASA Astrophysics Data System (ADS)

    2008-12-01

    When African leaders met in Lagos, Nigeria, in April 1980 to devise a plan for economic development, they underlined the importance of science and technology with a pledge that each country should spend at least 1% of its GDP on research and development. Nearly 30 years later, the Lagos promise remains largely unfulfilled. Indeed, at a meeting of the African Union in Addis Ababa, Ethiopia, in January last year, the heads of state reiterated the need to increase funding for research and development to 1% by 2010.

  8. Inference of Evolutionary Jumps in Large Phylogenies using Lévy Processes.

    PubMed

    Duchen, Pablo; Leuenberger, Christoph; Szilágyi, Sándor M; Harmon, Luke; Eastman, Jonathan; Schweizer, Manuel; Wegmann, Daniel

    2017-11-01

    Although it is now widely accepted that the rate of phenotypic evolution may not necessarily be constant across large phylogenies, the frequency and phylogenetic position of periods of rapid evolution remain unclear. In his highly influential view of evolution, G. G. Simpson supposed that such evolutionary jumps occur when organisms transition into so-called new adaptive zones, for instance after dispersal into a new geographic area, after rapid climatic changes, or following the appearance of an evolutionary novelty. Only recently, large, accurate and well calibrated phylogenies have become available that allow testing this hypothesis directly, yet inferring evolutionary jumps remains computationally very challenging. Here, we develop a computationally highly efficient algorithm to accurately infer the rate and strength of evolutionary jumps as well as their phylogenetic location. Following previous work we model evolutionary jumps as a compound process, but introduce a novel approach to sample jump configurations that does not require matrix inversions and thus naturally scales to large trees. We then make use of this development to infer evolutionary jumps in Anolis lizards and Loriinii parrots where we find strong signal for such jumps at the basis of clades that transitioned into new adaptive zones, just as postulated by Simpson's hypothesis. [evolutionary jump; Lévy process; phenotypic evolution; punctuated equilibrium; quantitative traits. The Author(s) 2017. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

  9. Two-stage optics - High-acuity performance from low-acuity optical systems

    NASA Technical Reports Server (NTRS)

    Meinel, Aden B.; Meinel, Marjorie P.

    1992-01-01

    The concept of two-stage optics, developed under a program to enhance the performance, lower the cost, and increase the reliability of the 20-m Large Deployable Telescope, is examined. The concept permits the large primary mirror to remain as deployed or as space-assembled, with phasing and subsequent control of the system done by a small fully assembled optical active element placed at an exit pupil. The technique is being applied to correction of the fabrication/testing error in the Hubble Space Telescope primary mirror. The advantages offered by this concept for very large space telescopes are discussed.

  10. Unpacking Everyday "Teacher Talk" about Students and Families of Color: Implications for Teacher and School Leader Development

    ERIC Educational Resources Information Center

    Pollack, Terry M.

    2013-01-01

    Informal "teacher talk" about students is ubiquitous, but it remains largely unexamined. This study critically examines casual, everyday teacher discourse about students perceived to be racially or culturally "different." Data were collected through participants' journal entries, group discussion, and interviews. Findings…

  11. Specifying the Links between Household Chaos and Preschool Children's Development

    ERIC Educational Resources Information Center

    Martin, Anne; Razza, Rachel A.; Brooks-Gunn, Jeanne

    2012-01-01

    Household chaos has been linked to poorer cognitive, behavioural, and self-regulatory outcomes in young children, but the mechanisms responsible remain largely unknown. Using a diverse sample of families in Chicago, the present study tests for the independent contributions made by five indicators of household chaos: noise, crowding, family…

  12. SETTING EXPECTATIONS FOR THE OHIO RIVER FISH INDEX BASED ON IN-STREAM HABITAT

    EPA Science Inventory

    The use of habitat criteria for setting fish community assessment expectations is common for streams, but a standard approach for great rivers remains largely undeveloped. We developed assessment expectations for the Ohio River Fish Index (ORFIN) based on measures of in-stream h...

  13. Sensory Impairments and Autism: A Re-Examination of Causal Modelling

    ERIC Educational Resources Information Center

    Gerrard, Sue; Rugg, Gordon

    2009-01-01

    Sensory impairments are widely reported in autism, but remain largely unexplained by existing models. This article examines Kanner's causal reasoning and identifies unsupported assumptions implicit in later empirical work. Our analysis supports a heterogeneous causal model for autistic characteristics. We propose that the development of a…

  14. Characterization of spermidine hydroxycinnamoyl transferases from eggplant (Solanum melongena L.) and its wild relative Solanum richardii Dunal

    USDA-ARS?s Scientific Manuscript database

    Eggplant produces a variety of hydroxycinnamic acid amides (HCAAs) that play an important role in plant development and adaptation to environmental changes. However, the HCAA pathway remains largely uncharacterized in Solanaceae. In this study, a spermidine hydroxycinnamoyl transferase (SHT) from eg...

  15. Integrating Knowledge, Skills and Attitudes: Conceptualising Learning Processes towards Vocational Competence

    ERIC Educational Resources Information Center

    Baartman, Liesbeth K. J.; de Bruijn, Elly

    2011-01-01

    Current research focuses on competence development and complex professional tasks. However, "learning processes" towards the integration of knowledge, skills and attitudes largely remain a black box. This article conceptualises three integration processes, in analogy to theories on transfer. Knowledge, skills and attitudes are defined, reconciling…

  16. Drosophila Kruppel homolog 1 represses lipolysis through interactions with dFOXO

    USDA-ARS?s Scientific Manuscript database

    Juvenile hormone (JH) is a key endocrine signal involved in insect molting and metamorphosis. Recent studies suggest that JH is involved in not only development programming, but also in metabolic control. However, how JH modulates metabolism remains largely unknown. It has been shown that JH induces...

  17. Locational trends in R and D by large US corporations, 1965 to 1977

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

    Malecki, E.J.

    1979-10-01

    The locational decisions of large corporations, especially those involving research and development (R and D) and its role in technological change, have considerable effects on regional economic development. The locations of R and D facilities of 330 firms in the United States, are found primarily in metropolitan areas. Industry-specific patterns are present, but overall, a small number of major urban areas are the locations of corporate R and D. Changes in these patterns from 1965 to 1977 show that gains in R and D have taken place in only a few northeastern cities and in relatively few (SMSAs) Standard Metropolitanmore » Statistical Areas, in the Sunbelt. A second major shift in R and D is outward from some large cities, but within their urban regions. Corporate R and D, although experiencing some locational shifts, is remaining quite concentrated in large metropolitan areas. 47 references, 7 tables.« less

  18. [Diverticular disease of the large bowel - surgical treatment].

    PubMed

    Levý, M; Herdegen, P; Sutoris, K; Simša, J

    2013-07-01

    Surgical treatment, despite the rapid development of the numerous modern miniinvasive intervention techniques, remains essential in the treatment of complicated diverticular disease. The aim of this work is to summarize indications for surgical treatment in both acute and elective patients suffering from diverticular disease of the large bowel. Review of the literature and recent findings concerning indications for surgical intervention in patients with diverticulosis of the colon. The article describes indications, types of procedures, techniques and postoperative care in patients undergoing surgical intervention for diverticular disease.

  19. Drug development in neuropsychopharmacology.

    PubMed

    Fritze, Jürgen

    2008-03-01

    Personalized medicine is still in its infancy concerning drug development in neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug response and/or tolerability and safety largely remain to be identified. Possibly, this kind of personalized medicine will first gain clinical relevance in the dementias. The clinical relevance of the genotyping of drug-metabolizing enzymes as suggested by drug licensing authorities for the pharmacokinetic evaluation of medicinal products needs to be proven in sound clinical trials.

  20. [The role of the right hemisphere on recovery from Wernicke's aphasia].

    PubMed

    Tabuchi, M; Fujii, T; Yamadori, A; Onodera, K; Endou, K

    1998-04-01

    We report a rare case of severe Wernicke's aphasia who showed a rapid and surprisingly good recovery despite of a large infarct involving the left posterior language area. A 68-year-old right-handed woman without a family history of left-handedness developed a severe comprehension difficulty and paraphasic output following a large infarct in the left posterior temporoparietal region. However, in 6 weeks, naming, comprehension, and repetition of words became almost normal. Spontaneous speech also became almost normal, although comprehension and repetition of sentences remained slightly impaired. The lesion size remained unchanged. A dichotic listening test 4 months after the onset showed clear left ear superiority. We speculate from these observations that the dormant language function in the right hemisphere might have played a role for rapid and good recovery of this case.

  1. Development of a large inert gas ion thruster

    NASA Technical Reports Server (NTRS)

    Steiner, G.

    1982-01-01

    A 30 cm inert gas electrostatic ion thruster has been developed, exhibiting excellent performance. In the development, the effective anode area was reduced by altering the magnetic field geometry to improve plasma containment, consistent with operational stability. The propellant introduction scheme has the effect of 'folding' the discharge chamber without the increased wall loss penalty associated with a longer chamber. These features contribute to a low discharge cost (eV/ion) versus mass utilization characteristic which remains relatively flat even to high mass utilizations.

  2. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours | Office of Cancer Genomics

    Cancer.gov

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails.

  3. On the Crest of a Wave: A Review of Wave Power Technology

    ERIC Educational Resources Information Center

    Harris, Fank

    2014-01-01

    The energy potentially available from waves around the coast of the UK far exceeds our domestic and industrial demands and yet, despite much research, numerous patent applications and several pilot schemes, the exploitation of waves for their energy largely remains in transition between development and commercialisation. This article examines the…

  4. Positive Behavior Support for a Child with Inattentive Behavior in a Japanese Regular Classroom

    ERIC Educational Resources Information Center

    Baba, Chiharu; Tanaka-Matsumi, Junko

    2011-01-01

    Nondisruptive problem behaviors exist to a large extent in group-oriented Japanese regular classrooms. However, many children remain untreated. We implemented an antecedent-based functional behavioral assessment (FBA) and developed a behavioral support program for a first-grade boy who exhibited inattentive behavior in a Japanese regular…

  5. Activities for Babies and Toddlers with Down Syndrome: A Physiotherapy Approach.

    ERIC Educational Resources Information Center

    Kelso, Rose-Anne; Price, Sue

    Children with Down Syndrome have the potential for the development of a large range and variety of postures, balance reactions, movements, and skills. Sometimes this potential remains relatively untapped resulting in unusual, inefficient, or even detrimental patterns of movement. By handling and playing with the child, he or she becomes more aware…

  6. Maritime security report. April 1997 [Maritime smuggling of drugs and contraband goods through Haiti adversely impacting legitimate commerce and development; Partnering : a key to growing challenges confronting maritime security

    DOT National Transportation Integrated Search

    1997-04-01

    Haiti is a significant transshipment conduit for South American cocaine destined for the United States. This smuggling is facilitated by Haitis system of seaports which remain largely unmonitored. Smuggling and trafficking contraband merchandise aver...

  7. Aerobic Exercise and Other Healthy Lifestyle Factors That Influence Vascular Aging

    ERIC Educational Resources Information Center

    Santos-Parker, Jessica R.; LaRocca, Thomas J.; Seals, Douglas R

    2014-01-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development…

  8. Reforming the Higher Education System in Iraq: Internationalization via Decentralization

    ERIC Educational Resources Information Center

    Al-Janabi, Sufyan T. Faraj; Anderson, David

    2011-01-01

    In countries where higher education has largely been a state function, conservative bureaucracies are viewed as impediments to necessary development and change. Virtually everywhere, voices are raised to demand necessary reforms yet, in spite of these apparently common challenges, it remains true that policy-related education issues are framed by…

  9. California DREAMers: Activism, Identity, and Empowerment among Undocumented College Students

    ERIC Educational Resources Information Center

    DeAngelo, Linda; Schuster, Maximilian T.; Stebleton, Michael J.

    2016-01-01

    There is a large gap in college access and success for undocumented students. This emergent population remains uniquely and precariously situated within campus environments, despite the passage of Development, Relief, and Education for Alien Minors (DREAM) Acts in some states. These inequities have sparked activism for DREAMers associated with the…

  10. Using Narratives to Develop a Hermeneutic Understanding of HIV/AIDS in South Africa

    ERIC Educational Resources Information Center

    Baxen, Jean

    2008-01-01

    Constructions of the HIV/AIDS pandemic are largely influenced by the dominant discourses of sexuality and disease. Deeply embedded in positivistic frames of references that favour conceptions of a medicalised and/or moralised body which operates contextually and socially detached, these discourses remain those that, in the main, frame…

  11. An RNA-seq transcriptome analysis of orthophosphate-deficient white lupin reveals novel insights into phosphorus acclimation in plants

    USDA-ARS?s Scientific Manuscript database

    Phosphorus (P) is one of the most limiting macronutrients in soils for plant growth and development. However, the whole genome molecular mechanisms contributing to plant acclimation to Pi-deficiency remains largely unknown. White lupin (Lupinus albus L.) has evolved unique adaptation systems for gro...

  12. Development of L2 Interactional Resources for Online Collaborative Task Accomplishment

    ERIC Educational Resources Information Center

    Balaman, Ufuk; Sert, Olcay

    2017-01-01

    Technology-mediated task environments have long been considered integral parts of L2 learning and teaching processes. However, the interactional resources that the learners deploy to complete tasks in these environments have remained largely unexplored due to an overall focus on task design and outcomes rather than task engagement processes. With…

  13. A Theory-Grounded Measure of Adolescents' Response to a Media Literacy Intervention

    ERIC Educational Resources Information Center

    Greene, Kathryn; Yanovitzky, Itzhak; Carpenter, Amanda; Banerjee, Smita C.; Magsamen-Conrad, Kate; Hecht, Michael L.; Elek, Elvira

    2015-01-01

    Media literacy interventions offer promising avenues for the prevention of risky health behaviors among children and adolescents, but current literature remains largely equivocal about their efficacy. The primary objective of this study was to develop and test theoretically-grounded measures of audiences' degree of engagement with the content of…

  14. Global Patterns in Students' Views of Science and Interest in Science

    ERIC Educational Resources Information Center

    van Griethuijsen, Ralf A. L. F.; van Eijck, Michiel W.; Haste, Helen; den Brok, Perry J.; Skinner, Nigel C.; Mansour, Nasser; Savran Gencer, Ayse; BouJaoude, Saouma

    2015-01-01

    International studies have shown that interest in science and technology among primary and secondary school students in Western European countries is low and seems to be decreasing. In many countries outside Europe, and especially in developing countries, interest in science and technology remains strong. As part of the large-scale European Union…

  15. Moving zone Marangoni drying of wet objects using naturally evaporated solvent vapor

    DOEpatents

    Britten, Jerald A.

    1997-01-01

    A surface tension gradient driven flow (a Marangoni flow) is used to remove the thin film of water remaining on the surface of an object following rinsing. The process passively introduces by natural evaporation and diffusion of minute amounts of alcohol (or other suitable material) vapor in the immediate vicinity of a continuously refreshed meniscus of deionized water or another aqueous-based, nonsurfactant rinsing agent. Used in conjunction with cleaning, developing or wet etching application, rinsing coupled with Marangoni drying provides a single-step process for 1) cleaning, developing or etching, 2) rinsing, and 3) drying objects such as flat substrates or coatings on flat substrates without necessarily using heat, forced air flow, contact wiping, centrifugation or large amounts of flammable solvents. This process is useful in one-step cleaning and drying of large flat optical substrates, one-step developing/rinsing and drying or etching/rinsing/drying of large flat patterned substrates and flat panel displays during lithographic processing, and room-temperature rinsing/drying of other large parts, sheets or continuous rolls of material.

  16. Moving zone Marangoni drying of wet objects using naturally evaporated solvent vapor

    DOEpatents

    Britten, J.A.

    1997-08-26

    A surface tension gradient driven flow (a Marangoni flow) is used to remove the thin film of water remaining on the surface of an object following rinsing. The process passively introduces by natural evaporation and diffusion of minute amounts of alcohol (or other suitable material) vapor in the immediate vicinity of a continuously refreshed meniscus of deionized water or another aqueous-based, nonsurfactant rinsing agent. Used in conjunction with cleaning, developing or wet etching application, rinsing coupled with Marangoni drying provides a single-step process for (1) cleaning, developing or etching, (2) rinsing, and (3) drying objects such as flat substrates or coatings on flat substrates without necessarily using heat, forced air flow, contact wiping, centrifugation or large amounts of flammable solvents. This process is useful in one-step cleaning and drying of large flat optical substrates, one-step developing/rinsing and drying or etching/rinsing/drying of large flat patterned substrates and flat panel displays during lithographic processing, and room-temperature rinsing/drying of other large parts, sheets or continuous rolls of material. 5 figs.

  17. [A new look at the tomb of the physician, Morlongo Venice].

    PubMed

    Pardon-Labonnelie, Muriel

    2014-01-01

    The development of the inventory and synthetic study of collyrium stamps, commonly known as "oculist's stamps", includes the physico-chemical analysis of rare stamped collyrium's remains. The fragments of collyrium which were discovered in a tomb of Morlungo (Veneto) are all the more remarkable as the remedy's name stamped on two of them remains enigmatic at the moment and because of the association in a funerary context with an-other thirty-five finds. More specifically, they were discovered near surgical bronze instruments, a large amount of amber, a portable sundial and a seal box. Recent archaeological, textual and technological data thus make the study of the remains of collyriums of Morlungo particularly interesting for the history of medicine.

  18. Fully developed turbulence in slugs of pipe flows

    NASA Astrophysics Data System (ADS)

    Cerbus, Rory; Liu, Chien-Chia; Sakakibara, Jun; Gioia, Gustavo; Chakraborty, Pinaki

    2015-11-01

    Despite over a century of research, transition to turbulence in pipe flows remains a mystery. In theory the flow remains laminar for arbitrarily large Reynolds number, Re. In practice, however, the flow transitions to turbulence at a finite Re whose value depends on the disturbance, natural or artificial, in the experimental setup. The flow remains in the transition state for a range of Re ~ 0 (1000) ; for larger Re the flow becomes fully developed. The transition state for Re > 3000 consists of axially segregated regions of laminar and turbulent patches. These turbulent patches, known as slugs, grow as they move downstream. Their lengths span anywhere between a few pipe diameters to the whole length of the pipe. Here we report Stereo Particle Image Velocimetry measurements in the cross-section of the slugs. Notwithstanding the continuous growth of the slugs, we find that the mean velocity and stress profiles in the slugs are indistinguishable from that of statistically-stationary fully-developed turbulent flows. Our results are independent of the length of the slugs. We contrast our results with the well-known work of Wygnanski & Champagne (1973), whose measurements, we argue, are insufficient to draw a clear conclusion regarding fully developed turbulence in slugs.

  19. Adult Learning--Providing Equal Opportunities or Widening Differences? The Polish Case

    ERIC Educational Resources Information Center

    Kocór, Marcin; Worek, Barbara

    2017-01-01

    Educational activity among adults is not only a key factor of social development but also one of the most important priorities of public policies. Although large sums have been earmarked and numerous actions undertaken to encourage adult learning, many people remain educationally passive, a particularly acute problem in Poland. We point to the…

  20. 24 CFR 968.103 - Allocation of funds under section 14.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... from previous years may remain in the reserve until allocated. The requirements governing the reserve... year cap. (Weighted at 206.5); (5) In the case of a large agency, the number of units with 2 or more... 5 years after such reduction, and consists of 50 percent of the published Total Development Cost for...

  1. 24 CFR 968.103 - Allocation of funds under section 14.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... from previous years may remain in the reserve until allocated. The requirements governing the reserve... year cap. (Weighted at 206.5); (5) In the case of a large agency, the number of units with 2 or more... 5 years after such reduction, and consists of 50 percent of the published Total Development Cost for...

  2. Thinning effects on tree mortality and snag recruitment in western Oregon

    Treesearch

    Erich Kyle Dodson; Klaus J. Puettmann; Adrian Ares

    2013-01-01

    Tree mortality shapes forest structural development and the resulting dead wood provides habitat for many species. However, the eff ects of thinning on mortality and large snag recruitment have been variable and remain poorly understood. We examined thinning eff ects on tree mortality at eleven Density Management Study (DMS) sites in western Oregon. Th inning reduced...

  3. Learning to Make Sense: What Works in Entrepreneurial Education?

    ERIC Educational Resources Information Center

    Higgins, David; Elliott, Chris

    2011-01-01

    Purpose: The paper aims to explore the changing influences and relevance of passive and experiential methods of learning within what can be described as a new era of entrepreneurial education. What still largely remains unaddressed in the literature is how are entrepreneur's best educated and developed in a manner which can have a direct impact on…

  4. Community Collaborations and Youth Development: Preliminary Findings on the State of the Evidence. Research Brief Series

    ERIC Educational Resources Information Center

    Center for Promise, 2013

    2013-01-01

    In 2004, the Aspen Institute Roundtable on Community Change emphasized the need for a comprehensive base of information on the effectiveness of community collaborations for youth--an accessible, evidence-rich resource that could guide local efforts to bring about meaningful change. Nearly 10 years later, this need remains largely unmet. In…

  5. Reintroducing fire in regenerated dry forests following stand-replacing wildfire.

    Treesearch

    David W. Peterson; Paul F. Hessburg; Brion Salter; Kevin M. James; Matthew C. Dahlgreen; John A. Barnes

    2007-01-01

    Prescribed fire use may be effective for increasing fire resilience in young coniferous forests by reducing surface fuels, modifying overstory stand structure, and promoting development of large trees of fire resistant species. Questions remain, however, about when and how to reintroduce fire in regenerated forests, and to what end. We studied the effects of spring...

  6. Near-source mobile methane emission estimates using EPA Method33a and a novel probabilistic approach as a basis for leak quantification in urban areas

    EPA Science Inventory

    Methane emissions from underground pipeline leaks remain an ongoing issue in the development of accurate methane emission inventories for the natural gas supply chain. Application of mobile methods during routine street surveys would help address this issue, but there are large ...

  7. Learning Analysis of K-12 Students' Online Problem Solving: A Three-Stage Assessment Approach

    ERIC Educational Resources Information Center

    Hu, Yiling; Wu, Bian; Gu, Xiaoqing

    2017-01-01

    Problem solving is considered a fundamental human skill. However, large-scale assessment of problem solving in K-12 education remains a challenging task. Researchers have argued for the development of an enhanced assessment approach through joint effort from multiple disciplines. In this study, a three-stage approach based on an evidence-centered…

  8. Cell birth, cell death, cell diversity and DNA breaks: how do they all fit together?

    NASA Technical Reports Server (NTRS)

    Gilmore, E. C.; Nowakowski, R. S.; Caviness, V. S. Jr; Herrup, K.

    2000-01-01

    Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that are deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale, yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired. The cause and natural function of such breaks remains a mystery; however, their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes. If this is true, the target gene(s) of recombination and their significance remain to be determined.

  9. The development of young siblings of children with autism from 4 to 54 months.

    PubMed

    Gamliel, Ifat; Yirmiya, Nurit; Sigman, Marian

    2007-01-01

    Cognitive and language skills of 39 siblings of children with autism (SIBS-A) and 39 siblings of typically developing children (SIBS-TD) at ages 4, 14, 24, 36, and 54 months were compared. Twelve of the 39 SIBS-A revealed a delay in cognition and/or language (including one child diagnosed with autism) compared to only two SIBS-TD. Developmental trajectories revealed that the cognitive differences disappeared by age 54 months, but some differences in language ability remained. Thus, most SIBS-A were well-functioning, but some revealed cognitive and/or language difficulties during the preschool years. Even these siblings by and large caught up by the age of 54 months, with receptive and expressive language abilities remaining an area of difficulty for some earlier identified siblings.

  10. Impacts of policy and market incentives for solid waste recycling in Dhaka, Bangladesh.

    PubMed

    Matter, Anne; Ahsan, Mehedi; Marbach, Michelle; Zurbrügg, Christian

    2015-05-01

    Solid waste mismanagement in Dhaka, Bangladesh, illustrates a well-known market failure which can be summarized as: waste is a resource in the wrong place. Inorganic materials such as plastic or paper can be used to feed the demand for recycled materials in the industrial sector. Organic materials can be converted and used in the nutrient-starved agricultural sector which is currently heavily depending on chemical fertilizers. They are also a feedstock to generate renewable energy in the form of biogas for this energy-starved country relying on diminishing natural gas reserves and increasing import of coal. Reality however does not capitalize on this potential; instead the waste is a burden for municipal authorities who spend large portions of their budgets attempting to transport it out of the city for discharge into landfills. The major part of these materials still remains uncollected in the residential areas and is discarded indiscriminately in open spaces, polluting the residents' living environment including water, soil and air resources, in the city and beyond. Bangladeshi authorities have, to some extent, recognized this market failure and have developed policies to encourage the development of waste recycling activities. It is also important to note that this market failure is only partial: a large, mostly informal recycling sector has developed in Bangladesh, focusing on inorganic recyclables of market value. The fact that this sector remains largely informal means that these actors perceive significant barriers to formalization. Comparatively, the organic waste recycling sector is less driven by market mechanisms. Competition from chemical fertilizers and fossil fuels is fierce and hinders the development of market opportunities for compost and renewable energy. Nevertheless commercial production of compost and biogas from organic municipal waste is formalized and benefiting from policy incentives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Development costs of reusable launch vehicles

    NASA Astrophysics Data System (ADS)

    Koelle, D.

    2002-07-01

    The paper deals first with the definition and understanding of "Development Costs" in general. Usually there is large difference between initial "development cost guesses", "Proposal Cost Estimations" and the final "Cost-to-Completion". The reasons for the usual development cost increases during development are discussed. The second part discusses the range of historic launch systems' development costs under "Business-as-Usual" (BaU) - Conditions and potential cost reductions for future developments of RLVs, as well as the comparison to commercial, industrial development cost. Part three covers the potential reduction of development cost by application of "Cost Engineering Principles". An example of the large potential cost range (between 6 and 17 Billion USD) for the development of the same winged rocket-propelled SSTO launch vehicle concept is presented. Finally the tremendous development cost differences are shown which exist for the different potential Reusable Launch System Options which are under discussion. There remains an unresolved problem between the primary goals of the national space agencies with emphasis on new technology development/national prestige and the commercial market requirement of a simple low-cost RLV-System.

  12. Dispersion in Rectangular Networks: Effective Diffusivity and Large-Deviation Rate Function

    NASA Astrophysics Data System (ADS)

    Tzella, Alexandra; Vanneste, Jacques

    2016-09-01

    The dispersion of a diffusive scalar in a fluid flowing through a network has many applications including to biological flows, porous media, water supply, and urban pollution. Motivated by this, we develop a large-deviation theory that predicts the evolution of the concentration of a scalar released in a rectangular network in the limit of large time t ≫1 . This theory provides an approximation for the concentration that remains valid for large distances from the center of mass, specifically for distances up to O (t ) and thus much beyond the O (t1 /2) range where a standard Gaussian approximation holds. A byproduct of the approach is a closed-form expression for the effective diffusivity tensor that governs this Gaussian approximation. Monte Carlo simulations of Brownian particles confirm the large-deviation results and demonstrate their effectiveness in describing the scalar distribution when t is only moderately large.

  13. Prepreg and Melt Infiltration Technology Developed for Affordable, Robust Manufacturing of Ceramic Matrix Composites

    NASA Technical Reports Server (NTRS)

    Singh, Mrityunjay; Petko, Jeannie F.

    2004-01-01

    Affordable fiber-reinforced ceramic matrix composites with multifunctional properties are critically needed for high-temperature aerospace and space transportation applications. These materials have various applications in advanced high-efficiency and high-performance engines, airframe and propulsion components for next-generation launch vehicles, and components for land-based systems. A number of these applications require materials with specific functional characteristics: for example, thick component, hybrid layups for environmental durability and stress management, and self-healing and smart composite matrices. At present, with limited success and very high cost, traditional composite fabrication technologies have been utilized to manufacture some large, complex-shape components of these materials. However, many challenges still remain in developing affordable, robust, and flexible manufacturing technologies for large, complex-shape components with multifunctional properties. The prepreg and melt infiltration (PREMI) technology provides an affordable and robust manufacturing route for low-cost, large-scale production of multifunctional ceramic composite components.

  14. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders.

    PubMed

    Gurwitz, David

    2016-09-01

    The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

  15. The Role of Policy and Institutions on Health Spending.

    PubMed

    de la Maisonneuve, Christine; Moreno-Serra, Rodrigo; Murtin, Fabrice; Oliveira Martins, Joaquim

    2017-07-01

    This paper investigates the impact of policies and institutions on health expenditures for a large panel of Organisation for Economic Co-operation and Development countries for the period of 2000-2010. A set of 20 policy and institutional indicators developed by the Organisation for Economic Co-operation and Development are integrated into a theoretically motivated econometric framework, alongside control variables related to demographic (dependency ratio) and non-demographic (income, prices and technology) drivers of health expenditures per capita. Although a large share of cross-country differences in public health expenditures can be explained by demographic and economic factors (around 71%), cross-country variations in policies and institutions also have a significant influence, explaining most of the remaining difference in public health spending (23%). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Human Gut Microbiome: Function Matters.

    PubMed

    Heintz-Buschart, Anna; Wilmes, Paul

    2017-11-22

    The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction.

    PubMed

    Gosselin, H; Qi, X; Rouleau, J L

    1998-01-01

    Early after infarction, ventricular dysfunction occurs as a result of loss of myocardial tissue. Although papillary muscle studies suggest that reduced myocardial contractility contributes to this ventricular dysfunction, in vivo studies indicate that at rest, cardiac output is normal or near normal, suggesting that contractility of the remaining viable myocardium of the ventricular wall is preserved. However, this has never been verified. To explore this further, 100 rats with various-sized myocardial infarctions had ventricular function assessed by Langendorff preparation or by isolated papillary muscle studies 5 weeks after infarction. Morphologic studies were also done. Rats with large infarctions (54%) had marked ventricular dilatation (dilatation index from 0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7 to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease less than one would expect with an infarct size of 54%. The contractility of the remaining viable myocardium of the ventricle was also moderately depressed (peak systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions (32%) had less marked but still moderate ventricular dilatation (dilatation index 0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2 g/mm2, p < 0.01). However, their decrease in ventricular function was only mild (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect with an infarct size of 32%. The remaining viable myocardium of the ventricular wall appeared to have normal contractility (peak systolic midwall stress = 86 mmHg, ns). We conclude that in this postinfarction model, in large myocardial infarctions, a loss of contractility of the remaining viable myocardium of the ventricular wall occurs as early as 5 weeks after infarction and that papillary muscle studies slightly overestimate the degree of ventricular dysfunction. In moderate infarctions, the remaining viable myocardium of the ventricular wall has preserved contractility while papillary muscle function is depressed. In this relatively early postinfarction phase, ventricular remodelling appears to help maintain left ventricular function in both moderate and large infarctions.

  18. [Categories and characteristics of BPH drug evaluation models: a comparative study].

    PubMed

    Huang, Dong-Yan; Wu, Jian-Hui; Sun, Zu-Yue

    2014-02-01

    Benign prostatic hyperplasia (BPH) is a worldwide common disease in men over 50 years old, and the exact cause of BPH remains largely unknown. In order to elucidate its pathogenesis and screen effective drugs for the treatment of BPH, many BPH models have been developed at home and abroad. This article presents a comprehensive analysis of the categories and characteristics of BPH drug evaluation models, highlighting the application value of each model, to provide a theoretical basis for the development of BPH drugs.

  19. Telehealth and Indian healthcare: moving to scale and sustainability.

    PubMed

    Carroll, Mark; Horton, Mark B

    2013-05-01

    Telehealth innovation has brought important improvements in access to quality healthcare for American Indian and Alaska Native communities. Despite these improvements, substantive work remains before telehealth capability can be more available and sustainable across Indian healthcare. Some of this work will rely on system change guided by new care model development. Such care model development depends on expansion of telehealth reimbursement. The U.S. Indian healthcare system is an ideal framework for implementing and evaluating large-scale change in U.S. telehealth reimbursement policy.

  20. Development and management of a geographic information system for health research in a developing-country setting: a case study from Bangladesh.

    PubMed

    Sugimoto, Jonathan D; Labrique, Alain B; Ahmad, Salahuddin; Rashid, Mahbubur; Klemm, Rolf D W; Christian, Parul; West, Keith P

    2007-12-01

    In the last decade, geographic information systems (GIS) have become accessible to researchers in developing countries, yet guidance remains sparse for developing a GIS. Drawing on experience in developing a GIS for a large community trial in rural Bangladesh, six stages for constructing, maintaining, and using a GIS for health research purposes were outlined. The system contains 0.25 million landmarks, including 150,000 houses, in an area of 435 sq km with over 650,000 people. Assuming access to reasonably accurate paper boundary maps of the intended working area and the absence of pre-existing digital local-area maps, the six stages are: to (a) digitize and update existing paper maps, (b) join the digitized maps into a large-area map, (c) reference this large-area map to a geographic coordinate system, (d) insert location landmarks of interest, (e) maintain the GIS, and (f) link it to other research databases. These basic steps can produce a household-level, updated, scaleable GIS that can both enhance field efficiency and support epidemiologic analyses of demographic patterns, diseases, and health outcomes.

  1. Development and Management of a Geographic Information System for Health Research in a Developing-country Setting: A Case Study from Bangladesh

    PubMed Central

    Sugimoto, Jonathan D.; Labrique, Alain B.; Salahuddin, Ahmad; Rashid, Mahbubur; Klemm, Rolf D.W.; Christian, Parul; West, Keith P.

    2007-01-01

    In the last decade, geographic information systems (GIS) have become accessible to researchers in developing countries, yet guidance remains sparse for developing a GIS. Drawing on experience in developing a GIS for a large community trial in rural Bangladesh, six stages for constructing, maintaining, and using a GIS for health research purposes were outlined. The system contains 0.25 million landmarks, including 150,000 houses, in an area of 435 sq km with over 650,000 people. Assuming access to reasonably accurate paper boundary maps of the intended working area and the absence of pre-existing digital local-area maps, the six stages are: to (a) digitize and update existing paper maps, (b) join the digitized maps into a large-area map, (c) reference this large-area map to a geographic coordinate system, (d) insert location landmarks of interest, (e) maintain the GIS, and (f) link it to other research databases. These basic steps can produce a household-level, updated, scaleable GIS that can both enhance field efficiency and support epidemiologic analyses of demographic patterns, diseases, and health outcomes. PMID:18402187

  2. From Service to Action? Students, Volunteering and Community Action in Mid Twentieth-Century Britain

    ERIC Educational Resources Information Center

    Brewis, Georgina

    2010-01-01

    Volunteering by higher education students in the UK has a long history which remains largely unexplored despite recent research and policy attention. This article offers a brief overview of the development of student volunteering before the 1960s and then discusses a shift from student social service to Student Community Action in the late 1960s…

  3. The Role of Curriculum in Fostering National Cohesion and Integration: Opportunities and Challenges. IBE Working Papers on Curriculum Issues No. 11

    ERIC Educational Resources Information Center

    Njeng'ere, David

    2014-01-01

    Curriculum planning emphasizes that education should serve to enable society to achieve its needs and aspirations. One such need in Kenya, which has remained largely elusive, is national cohesion and integration. Research has revealed that education contributes to the development of social capital by increasing individual propensity to trust and…

  4. 2010 U.S. Drinking Water Innovation Vendor Outlook - Report on the Companies and Market Trends Shaping Innovation in the U.S. Drinking Water Sector

    EPA Science Inventory

    Innovation in the water sector is unanimously viewed as critical to meeting water challenges that will emerge in the 21st century. However, a large number of open questions remain around the speed at which innovation must occur, where financing of development will come from, and ...

  5. 1997 Technology Applications Report,

    DTIC Science & Technology

    1997-01-01

    handle high -power loads at microwave radio frequencies , microwave vacuum tubes remain the chosen technology to amplify high power. Aria Microwave...structure called the active RF cavity amplifier (ARFCA). With this design , the amplifier handles high -power loads at radio and microwave frequencies ...developed this technology using BMDO-funded modeling methods designed to simulate the dynamics of large space-based structures. Because it increases

  6. Brain Development in Autism: Early Overgrowth Followed by Premature Arrest of Growth

    ERIC Educational Resources Information Center

    Courchesne, Eric

    2004-01-01

    Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies…

  7. The remains of the dam: what have we learned from 15 years of US dam removals?

    Treesearch

    Gordon E. Grant; Sarah L. Lewis

    2015-01-01

    Important goals for studying dam removal are to learn how rivers respond to large and rapid introductions of sediment, and to develop predictive models to guide future dam removals. Achieving these goals requires organizing case histories systematically so that underlying physical mechanisms determining rates and styles of sediment erosion, transport, and deposition...

  8. Supporting the Role of Associate Dean in Universities: An Alternative Approach to Management Development

    ERIC Educational Resources Information Center

    Preston, Diane; Floyd, Alan

    2016-01-01

    Located between senior management and academic staff, the role of the Associate Dean in universities appears to be growing in number, complexity and importance in recent years. A role arguably fraught with complexity, it remains largely undefined and under-researched. While little is known about the role in general, less still is known about their…

  9. Experimental Investigation of Very Large Model Wind Turbine Arrays

    NASA Astrophysics Data System (ADS)

    Charmanski, Kyle; Wosnik, Martin

    2013-11-01

    The decrease in energy yield in large wind farms (array losses) and associated revenue losses can be significant. When arrays are sufficiently large they can reach what is known as a fully developed wind turbine array boundary layer, or fully developed wind farm condition. This occurs when the turbulence statistics and the structure of the turbulence, within and above a wind farm, as well as the performance of the turbines remain the same from one row to the next. The study of this condition and how it is affected by parameters such as turbine spacing, power extraction, tip speed ratio, etc. is important for the optimization of large wind farms. An experimental investigation of the fully developed wind farm condition was conducted using a large array of porous disks (upstream) and realistically scaled 3-bladed wind turbines with a diameter of 0.25m. The turbines and porous disks were placed inside a naturally grown turbulent boundary layer in the 6m × 2.5m × 72m test section of the UNH Flow Physics Facility which can achieve test section velocities of up to 14 m/s and Reynolds numbers δ+ = δuτ / ν ~ 20 , 000 . Power, rate of rotation and rotor thrust were measured for select turbines, and hot-wire anemometry was used for flow measurements.

  10. Development of Eddy Current Techniques for the Detection of Cracking in Space Shuttle Primary Reaction Control Thrusters

    NASA Technical Reports Server (NTRS)

    Wincheski, Buzz A.; Simpson, John W.; Koshti, Ajay

    2007-01-01

    A recent identification of cracking in the Space Shuttle Primary Reaction Control System (PRCS) thrusters triggered an extensive nondestructive evaluation effort to develop techniques capable of identifying such damage on installed shuttle hardware. As a part of this effort, specially designed eddy current probes inserted into the acoustic cavity were explored for the detection of such flaws and for evaluation of the remaining material between the crack tip and acoustic cavity. The technique utilizes two orthogonal eddy current probes which are scanned under stepper motor control in the acoustic cavity to identify cracks hidden with as much as 0.060 remaining wall thickness to the cavity. As crack growth rates in this area have been determined to be very slow, such an inspection provides a large safety margin for continued operation of the critical shuttle hardware. Testing has been performed on thruster components with both actual and fabricated defects. This paper will review the design and performance of the developed eddy current inspection system. Detection of flaws as a function of remaining wall thickness will be presented along with the proposed system configuration for depot level or on-vehicle inspection capabilities.

  11. Development of Eddy Current Technique for the Detection of Stress Corrosion Cracking in Space Shuttle Primary Reaction Control Thrusters

    NASA Technical Reports Server (NTRS)

    Wincheski, Buzz; Simpson, John; Koshti, Ajay

    2006-01-01

    A recent identification of stress corrosion cracking in the Space Shuttle Primary Reaction Control System (PRCS) thrusters triggered an extensive nondestructive evaluation effort to develop techniques capable of identifying such damage on installed shuttle hardware. As a part of this effort, specially designed eddy current probes inserted into the acoustic cavity were explored for the detection of such flaws and for evaluation of the remaining material between the crack tip and acoustic cavity. The technique utilizes two orthogonal eddy current probes which are scanned under stepper motor control in the acoustic cavity to identify cracks hidden with as much as 0.060 remaining wall thickness to the cavity. As crack growth rates in this area have been determined to be very slow, such an inspection provides a large safety margin for continued operation of the critical shuttle hardware. Testing has been performed on thruster components with both actual and fabricated defects. This paper will review the design and performance of the developed eddy current inspection system. Detection of flaws as a function of remaining wall thickness will be presented along with the proposed system configuration for depot level or on-vehicle inspection capabilities.

  12. Joint CO2 and CH4 accountability for global warming

    PubMed Central

    Smith, Kirk R.; Desai, Manish A.; Rogers, Jamesine V.; Houghton, Richard A.

    2013-01-01

    We propose a transparent climate debt index incorporating both methane (CH4) and carbon dioxide (CO2) emissions. We develop national historic emissions databases for both greenhouse gases to 2005, justifying 1950 as the starting point for global perspectives. We include CO2 emissions from fossil sources [CO2(f)], as well as, in a separate analysis, land use change and forestry. We calculate the CO2(f) and CH4 remaining in the atmosphere in 2005 from 205 countries using the Intergovernmental Panel on Climate Change’s Fourth Assessment Report impulse response functions. We use these calculations to estimate the fraction of remaining global emissions due to each country, which is applied to total radiative forcing in 2005 to determine the combined climate debt from both greenhouse gases in units of milliwatts per square meter per country or microwatts per square meter per person, a metric we term international natural debt (IND). Australia becomes the most indebted large country per capita because of high CH4 emissions, overtaking the United States, which is highest for CO2(f). The differences between the INDs of developing and developed countries decline but remain large. We use IND to assess the relative reduction in IND from choosing between CO2(f) and CH4`control measures and to contrast the imposed versus experienced health impacts from climate change. Based on 2005 emissions, the same hypothetical impact on world 2050 IND could be achieved by decreasing CH4 emissions by 46% as stopping CO2 emissions entirely, but with substantial differences among countries, implying differential optimal strategies. Adding CH4 shifts the basic narrative about differential international accountability for climate change. PMID:23847202

  13. Joint CO2 and CH4 accountability for global warming.

    PubMed

    Smith, Kirk R; Desai, Manish A; Rogers, Jamesine V; Houghton, Richard A

    2013-07-30

    We propose a transparent climate debt index incorporating both methane (CH4) and carbon dioxide (CO2) emissions. We develop national historic emissions databases for both greenhouse gases to 2005, justifying 1950 as the starting point for global perspectives. We include CO2 emissions from fossil sources [CO2(f)], as well as, in a separate analysis, land use change and forestry. We calculate the CO2(f) and CH4 remaining in the atmosphere in 2005 from 205 countries using the Intergovernmental Panel on Climate Change's Fourth Assessment Report impulse response functions. We use these calculations to estimate the fraction of remaining global emissions due to each country, which is applied to total radiative forcing in 2005 to determine the combined climate debt from both greenhouse gases in units of milliwatts per square meter per country or microwatts per square meter per person, a metric we term international natural debt (IND). Australia becomes the most indebted large country per capita because of high CH4 emissions, overtaking the United States, which is highest for CO2(f). The differences between the INDs of developing and developed countries decline but remain large. We use IND to assess the relative reduction in IND from choosing between CO2(f) and CH4`control measures and to contrast the imposed versus experienced health impacts from climate change. Based on 2005 emissions, the same hypothetical impact on world 2050 IND could be achieved by decreasing CH4 emissions by 46% as stopping CO2 emissions entirely, but with substantial differences among countries, implying differential optimal strategies. Adding CH4 shifts the basic narrative about differential international accountability for climate change.

  14. [Robotic general surgery: where do we stand in 2013?].

    PubMed

    Buchs, Nicolas C; Pugin, François; Ris, Frédéric; Jung, Minoa; Hagen, Monika E; Volonté, Francesco; Azagury, Dan; Morel, Philippe

    2013-06-19

    While the number of publications concerning robotic surgery is increasing, the level of evidence remains to be improved. The safety of robotic approach has been largely demonstrated, even for complex procedures. Yet, the objective advantages of this technology are still lacking in several fields, notably in comparison to laparoscopy. On the other hand, the development of robotic surgery is on its way, as the enthusiasm of the public and the surgical community can testify. Still, clear clinical indications remain to be determined in the field of general surgery. The study aim is to review the current literature on robotic general surgery and to give the reader an overview in 2013.

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

    Schreck, S.; Sant, T.; Micallef, D.

    Wind turbine structures and components suffer excessive loads and premature failures when key aerodynamic phenomena are not well characterized, fail to be understood, or are inaccurately predicted. Turbine blade rotational augmentation remains incompletely characterized and understood, thus limiting robust prediction for design. Pertinent rotational augmentation research including experimental, theoretical, and computational work has been pursued for some time, but large scale wind tunnel testing is a relatively recent development for investigating wind turbine blade aerodynamics. Because of their large scale and complementary nature, the MEXICO and UAE Phase VI wind tunnel experiments offer unprecedented synergies to better characterize and understandmore » rotational augmentation of blade aerodynamics.« less

  16. Broadband metasurfaces enabling arbitrarily large delay-bandwidth products

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

    Ginis, Vincent; Tassin, Philippe; Koschny, Thomas

    2016-01-19

    Metasurfaces allow for advanced manipulation of optical signals by imposing phase discontinuities across flat interfaces. Unfortunately, these phase shifts remain restricted to values between 0 and 2π, limiting the delay-bandwidth product of such sheets. Here, we develop an analytical tool to design metasurfaces that mimic three-dimensional materials of arbitrary thickness. In this way, we demonstrate how large phase discontinuities can be realized by combining several subwavelength Lorentzian resonances in the unit cell of the surface. Finally, our methods open up the temporal response of metasurfaces and may lead to the construction of metasurfaces with a plethora of new optical functions.

  17. Dysphagia in the high-risk infant: potential factors and mechanisms123

    PubMed Central

    Jadcherla, Sudarshan

    2016-01-01

    Neonatal dysphagia, or abnormalities of swallowing, represent a major global problem, and consequences of dysfunctional feeding patterns carry over into infancy and toddler age groups. Growth, development, and independent feeding skills are all delayed among high-risk infants. Such a group comprises premature birth, low-birth-weight, congenital anomalies, perinatal asphyxia, postsurgical, and sepsis categories. The conflict between pathophysiologic and pragmatic feeding strategies remains a major conundrum and is largely due to a lack of validated diagnostic approaches amid heterogeneity of the patient phenotype. Thus, well-tested feeding management strategies that can be generalizable are lacking. Furthermore, the aerodigestive symptoms and signs, potential risk factors, and contributory etiologies remain nonspecific. This article presents mechanistic evidence related to the pathophysiologic basis of neonatal dysphagia as well as potential opportunities to improve feeding abilities and long-term development. PMID:26791178

  18. Immune tolerance: critical issues of factor dose, purity and treatment complications.

    PubMed

    DiMichele, D M

    2006-12-01

    The current practice of immune tolerance induction (ITI) therapy has been largely influenced by the results of small institutional studies and three large registries. However, many questions remain. Successful outcome predictors for ITI in haemophilia A have been suggested by the analyses of two of these registries. Among these predictors, factor VIII (FVIII) dose/dosing regimen remains a controversial outcome parameter, demonstrating a strong direct relationship to ITI success in the international registry and a weaker inverse relationship in the North American registry. There is an international multicentre prospective randomized trial underway to further study the role of FVIII dose in successful ITI induction in a good risk haemophilia A inhibitor patient cohort. FVIII purity also remains an unproved ITI outcome predictor. Institutional experience with von-Willebrand-factor-containing products has suggested its therapeutic advantage in both inhibitor development and eradication. The International ITI Study, although not designed to answer this particular question, may be able to determine an impact on outcome depending on the final distribution of investigator choice of product among the study subjects. Much less is known about the influence of factor IX (FIX) dose and purity on ITI success in haemophilia B. Importantly, nephrotic syndrome has been a major determinant of ITI failure in FIX inhibitor patients, particularly those with the allergic phenotype. Unfortunately, large prospective randomized trials in this group will not be feasible. Rather, we will have to rely on prospectively collected registry data to build our knowledge base of inhibitors and ITI in haemophilia B.

  19. Cost Modeling for Space Optical Telescope Assemblies

    NASA Technical Reports Server (NTRS)

    Stahl, H. Philip; Henrichs, Todd; Luedtke, Alexander; West, Miranda

    2011-01-01

    Parametric cost models are used to plan missions, compare concepts and justify technology investments. This paper reviews an on-going effort to develop cost modes for space telescopes. This paper summarizes the methodology used to develop cost models and documents how changes to the database have changed previously published preliminary cost models. While the cost models are evolving, the previously published findings remain valid: it costs less per square meter of collecting aperture to build a large telescope than a small telescope; technology development as a function of time reduces cost; and lower areal density telescopes cost more than more massive telescopes.

  20. Longitudinal Stability in Reading Comprehension Is Largely Heritable from Grades 1 to 6

    PubMed Central

    Soden, Brooke; Christopher, Micaela E.; Hulslander, Jacqueline; Olson, Richard K.; Cutting, Laurie; Keenan, Janice M.; Thompson, Lee A.; Wadsworth, Sally J.; Willcutt, Erik G.; Petrill, Stephen A.

    2015-01-01

    Reading comprehension is a foundational academic skill and significant attention has focused on reading development. This report is the first to examine the stability and change in genetic and environmental influences on reading comprehension across Grades 1 to 6. This developmental range is particularly important because it encompasses the timespan in which most children move from learning how to read to using reading for learning. Longitudinal simplex models were fitted separately for two independent twin samples (N = 706; N = 976). Results suggested that the shared environment contributed to variance in early but not later reading. Instead, stability in reading development was largely mediated by continuous genetic influences. Thus, although reading is clearly a learned skill and the environment remains important for reading development, individual differences in reading comprehension appear to be also influenced by a core of genetic stability that persists through the developmental course of reading. PMID:25602760

  1. Waste management CDM projects barriers NVivo 10® qualitative dataset.

    PubMed

    Bufoni, André Luiz; de Sousa Ferreira, Aracéli Cristina; Oliveira, Luciano Basto

    2017-12-01

    This article contains one NVivo 10® file with the complete 432 projects design documents (PDD) of seven waste management sector industries registered as Clean Development Mechanism (CDM) under United Nations Framework Convention on Climate Change (UNFCCC) Kyoto Protocol Initiative from 2004 to 2014. All data analyses and sample statistics made during the research remain in the file. We coded PDDs in 890 fragments of text, classified in five categories of barriers (nodes): technological, financial, human resources, regulatory, socio-political. The data supports the findings of author thesis [1] and other two indexed publication in Waste Management Journal: "The financial attractiveness assessment of large waste management projects registered as clean development mechanism" and "The declared barriers of the large developing countries waste management projects: The STAR model" [2], [3]. The data allows any computer assisted qualitative content analysis (CAQCA) on the sector and it is available at Mendeley [4].

  2. Injectable controlled release depots for large molecules

    PubMed Central

    Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

    2014-01-01

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

  3. Translation in cardiovascular stents and occluders: From biostable to fully degradable

    PubMed Central

    Huang, Yingying; Wong, Yee Shan; Ng, Herr Cheun Anthony; Boey, Freddy Y. C.

    2017-01-01

    Abstract Cardiovascular disease is a major cause of morbidity and mortality, especially in developed countries. Most academic research efforts in cardiovascular disease management focus on pharmacological interventions, or are concerned with discovering new disease markers for diagnosis and monitoring. Nonpharmacological interventions with therapeutic devices, conversely, are driven largely by novel materials and device design. Examples of such devices include coronary stents, heart valves, ventricular assist devices, and occluders for septal defects. Until recently, development of such devices remained largely with medical device companies. We trace the materials evolution story in two of these devices (stents and occluders), while also highlighting academic contributions, including our own, to the evolution story. Specifically, it addresses not only our successes, but also the challenges facing the translatability of concepts generated via academic research. PMID:29313029

  4. Worldwide Report, Nuclear Development and Proliferation

    DTIC Science & Technology

    1986-07-09

    Union’s Nuclear Disaster ? This reporter asked Vice Minister Zhou Ping: In your opinion, how should we view the Soviet Union’s recent nuclear accident...statement on Thurs- day announced that Bangladesh environment remained free from pullution follow- ing recent nuclear disaster at Chernobyl Nuclear...Chernobyl were based largely on nuclear disaster . American practice. However, a statement Mr Semark said de- issued yesterday by Es- tailed plans

  5. Black-White Residential Segregation: The Views of Myrdal in the 1940s and Trends of the 1980s.

    ERIC Educational Resources Information Center

    Farley, Reynolds

    1994-01-01

    Traces the development of black-white residential segregation in U.S. cities, and applies the views of Gunnar Myrdal, expressed in the 1940s, to housing trends in the 1980s. While such segregation has decreased, blacks remain more segregated than two other large minority groups (i.e., Hispanics and Asians). Forces influencing residential…

  6. Whole-tree utilization of southern pine advanced by developments in mechanical conversion

    Treesearch

    P. Koch

    1973-01-01

    In 1963 approximately 30 percent of the dry weight of above- and below-ground parts of southern pine trees ended as dry-surfaced lumber or paper; the remaining 70 percent was largely unused. By 1980, computer-controlled chipping headrigs, thin-kerf saws, lamination of lumber from rotary-cut veneer, high-yield pulping processes, and more intensive use of roots, bark,...

  7. Whole-tree utilization of southern pine advanced by developments in mechanical conversion

    Treesearch

    Peter Koch

    1973-01-01

    In 1963 approximately 30 percent of the dry weight of aboe- and below-ground parts of southern pine trees ended as dry-surfaced lumber or paper; the remaining 70 percent was largely unused. By 1980, computer-controlled chipping headrigs, think-kerf saws, lamination of lumber from rotary-cut veneer, high-yield pulping processes, and more intensive use of roots, bark,...

  8. Global Well-Posedness of the Boltzmann Equation with Large Amplitude Initial Data

    NASA Astrophysics Data System (ADS)

    Duan, Renjun; Huang, Feimin; Wang, Yong; Yang, Tong

    2017-07-01

    The global well-posedness of the Boltzmann equation with initial data of large amplitude has remained a long-standing open problem. In this paper, by developing a new {L^∞_xL^1v\\cap L^∞_{x,v}} approach, we prove the global existence and uniqueness of mild solutions to the Boltzmann equation in the whole space or torus for a class of initial data with bounded velocity-weighted {L^∞} norm under some smallness condition on the {L^1_xL^∞_v} norm as well as defect mass, energy and entropy so that the initial data allow large amplitude oscillations. Both the hard and soft potentials with angular cut-off are considered, and the large time behavior of solutions in the {L^∞_{x,v}} norm with explicit rates of convergence are also studied.

  9. Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development.

    PubMed

    Callens, Nina; Van Kuyk, Maaike; van Kuppenveld, Jet H; Drop, Stenvert L S; Cohen-Kettenis, Peggy T; Dessens, Arianne B

    2016-11-01

    The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Surfzone vorticity in the presence of extreme bathymetric variability

    NASA Astrophysics Data System (ADS)

    Clark, D.; Elgar, S.; Raubenheimer, B.

    2014-12-01

    Surfzone vorticity was measured at Duck, NC using a novel 5-m diameter vorticity sensor deployed in 1.75 m water depth. During the 4-week deployment the initially alongshore uniform bathymetry developed 200-m long mega-cusps with alongshore vertical changes of 1.5 m or more. When waves were small and the vorticity sensor was seaward of the surfzone, vorticity variance and mean vorticity varied with the tidally modulated water depth, consistent with a net seaward flux of surfzone-generated vorticity. Vorticity variance increased with incident wave heights up to 2-m. However, vorticity variance remained relatively constant for incident wave heights above 2-m, and suggests that eddy energy may become saturated in the inner surfzone during large wave events. In the presence of mega-cusps the mean vorticity (shear) is often large and generated by bathymetrically controlled rip currents, while vorticity variance remains strongly correlated with the incident wave height. Funded by NSF, ASD(R&E), and WHOI Coastal Ocean Institute.

  11. Large thermo-erosional tunnel for a river in northeast Greenland

    NASA Astrophysics Data System (ADS)

    Docherty, Catherine L.; Hannah, David M.; Riis, Tenna; Rosenhøj Leth, Simon; Milner, Alexander M.

    2017-12-01

    Thermo-erosional river bank undercutting is caused by the combined action of thermal and mechanical erosion of the permafrost by Arctic rivers whilst the overlying sediment withstands collapse temporarily. Here, we report the discovery of a large thermo-erosional tunnel that formed in the banks of a meltwater-fed stream in northeast Greenland in summer 2015. The tunnel was observed over eight days (14-22 July), during which period the tunnel remained open but bank-side slumping increased. Stream solute load increased immediately downstream and remained high 800 m from the tunnel. Whilst this field observation was opportunistic and information somewhat limited, our study provides a rare insight into an extreme event impacting permafrost, local geomorphology and stream habitat. With accelerated climate change in Arctic regions, increased permafrost degradation and warmer stream water temperature are predicted thereby enhancing potential for thermo-erosional niche development and associated stream bank slumping. This change could have significant implications for stream physicochemical habitat and, in turn, stream benthic communities, through changes in aquatic habitat conditions.

  12. Catastrophic antiphospholipid syndrome (Ronald Asherson syndrome) and obstetric pathology.

    PubMed

    Makatsariya, Alexander D; Khizroeva, Jamilya; Bitsadze, Viktoriya O

    2018-05-24

    Catastrophic antiphospholipid syndrome (CAPS) is an uncommon, often fatal, variant of the antiphospholipid syndrome (APS) that results in a widespread coagulopathy and high titres of antiphospholipid antibodies (aPL) and affects predominantly small vessels supplying organs with the development of multiorgan failure. It remains unclear why some patients develop the typical clinical picture of APS (thrombosis of large vessels), whereas others show the development of progressive microthrombosis, which the authors called "thrombotic storm" and multiple organ failure, that is, CAPS. Since 2001-2016, we discovered 17 patients with CAPS development. CAPS is life-threatening condition, but optimal treatment for CAPS is not developed yet and the mortality rate is as high as 30%-40%.

  13. Coal resources, reserves and peak coal production in the United States

    USGS Publications Warehouse

    Milici, Robert C.; Flores, Romeo M.; Stricker, Gary D.

    2013-01-01

    In spite of its large endowment of coal resources, recent studies have indicated that United States coal production is destined to reach a maximum and begin an irreversible decline sometime during the middle of the current century. However, studies and assessments illustrating coal reserve data essential for making accurate forecasts of United States coal production have not been compiled on a national basis. As a result, there is a great deal of uncertainty in the accuracy of the production forecasts. A very large percentage of the coal mined in the United States comes from a few large-scale mines (mega-mines) in the Powder River Basin of Wyoming and Montana. Reported reserves at these mines do not account for future potential reserves or for future development of technology that may make coal classified currently as resources into reserves in the future. In order to maintain United States coal production at or near current levels for an extended period of time, existing mines will eventually have to increase their recoverable reserves and/or new large-scale mines will have to be opened elsewhere. Accordingly, in order to facilitate energy planning for the United States, this paper suggests that probabilistic assessments of the remaining coal reserves in the country would improve long range forecasts of coal production. As it is in United States coal assessment projects currently being conducted, a major priority of probabilistic assessments would be to identify the numbers and sizes of remaining large blocks of coal capable of supporting large-scale mining operations for extended periods of time and to conduct economic evaluations of those resources.

  14. History of ball bearings

    NASA Technical Reports Server (NTRS)

    Dowson, D.; Hamrock, B. J.

    1981-01-01

    The familiar precision rolling-element bearings of the twentieth century are products of exacting technology and sophisticated science. Their very effectiveness and basic simplicity of form may discourage further interest in their history and development. Yet the full story covers a large portion of recorded history and surprising evidence of an early recognition of the advantages of rolling motion over sliding action and progress toward the development of rolling-element bearings. The development of rolling-element bearings is followed from the earliest civilizations to the end of the eighteenth century. The influence of general technological developments, particularly those concerned with the movement of large building blocks, road transportation, instruments, water-raising equipment, and windmills are discussed, together with the emergence of studies of the nature of rolling friction and the impact of economic factors. By 1800 the essential features of ball and rolling-element bearings had emerged and it only remained for precision manufacture and mass production to confirm the value of these fascinating machine elements.

  15. 3D Audio System

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Ames Research Center research into virtual reality led to the development of the Convolvotron, a high speed digital audio processing system that delivers three-dimensional sound over headphones. It consists of a two-card set designed for use with a personal computer. The Convolvotron's primary application is presentation of 3D audio signals over headphones. Four independent sound sources are filtered with large time-varying filters that compensate for motion. The perceived location of the sound remains constant. Possible applications are in air traffic control towers or airplane cockpits, hearing and perception research and virtual reality development.

  16. Packaging of silicon photonic devices: from prototypes to production

    NASA Astrophysics Data System (ADS)

    Morrissey, Padraic E.; Gradkowski, Kamil; Carroll, Lee; O'Brien, Peter

    2018-02-01

    The challenges associated with the photonic packaging of silicon devices is often underestimated and remains technically challenging. In this paper, we review some key enabling technologies that will allow us to overcome the current bottleneck in silicon photonic packaging; while also describing the recent developments in standardisation, including the establishment of PIXAPP as the worlds first open-access PIC packaging and assembly Pilot Line. These developments will allow the community to move from low volume prototype photonic packaged devices to large scale volume manufacturing, where the full commercialisation of PIC technology can be realised.

  17. Acoustics of old Asian bells

    NASA Astrophysics Data System (ADS)

    Rossing, Thomas D.

    2004-05-01

    The art of casting bronze bells developed to a high level of sophistication in China during the Shang dynasty (1766-1123 BC). Many chimes of two-tone bells remain from the Western and Eastern Zhou dynasties (1122-249 BC). With the spread of Buddhism from the third century, large round temple bells developed in China and later in Korea, Japan, and other Asian countries. Vibrational modes of some of these bells have been studied by means of holographic interferometry and experimental modal testing. Their musical as well as acoustical properties are discussed.

  18. An evaluation of very large airplanes and alternative fuels. Interim report

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

    Mikolowsky, W.T.; Noggle, L.W.; Hederman, W.F.

    1976-12-01

    Very large airplanes using alternative fuels are examined in the context of existing and possible future Air Force missions. Synthetic jet fuel (JP), liquid methane, liquid hydrogen, and nuclear propulsion are the fuel alternatives selected for detailed analysis. Conceptual designs of airplanes using each of these fuels were developed and estimates were made of their lifecycle cost and life-cycle energy consumption. Mission analyses were performed to determine the effectiveness of the alternative airplanes in strategic airlift specifically and in the station-keeping role in general. Results indicate that for most military applications airplanes with gross weights in excess of one millionmore » pounds promise to be superior to any comtemporary airplanes in terms of cost-effectiveness and energy-hydrocarbon jet fuel, whether manufactured from oil shale, coal or crude oil, remains the most attractive aviation fuel for future Air Force use. Policy recommendations are made pertaining both to alternative fuels and to advanced-technology large airplanes. Future research and developments are also identified.« less

  19. The endoplasmic reticulum: structure, function and response to cellular signaling.

    PubMed

    Schwarz, Dianne S; Blower, Michael D

    2016-01-01

    The endoplasmic reticulum (ER) is a large, dynamic structure that serves many roles in the cell including calcium storage, protein synthesis and lipid metabolism. The diverse functions of the ER are performed by distinct domains; consisting of tubules, sheets and the nuclear envelope. Several proteins that contribute to the overall architecture and dynamics of the ER have been identified, but many questions remain as to how the ER changes shape in response to cellular cues, cell type, cell cycle state and during development of the organism. Here we discuss what is known about the dynamics of the ER, what questions remain, and how coordinated responses add to the layers of regulation in this dynamic organelle.

  20. Thinking globally and acting locally in Mindanao: Supporting the delicate balance of future sustainability in South-East Asian wilderness as well as rural areas

    NASA Astrophysics Data System (ADS)

    Richards, C.

    2014-02-01

    Although models of future sustainability often talk about effectively balancing economic, social and environmental imperatives or factors, in practice this typically remains an elusive ideal. This paper explores the exemplary possibilities but also dilemmas of a proposed initiative in the resource-rich but under-developed Filippino island province of Mindanao to achieve such a delicate balance in practice. This initiative by Raintrust Sustainable Ventures' proposes to link foreign investment in agricultural development to both the social advancement of local tribal peoples and the protection of large amounts of remaining wilderness areas. Such a case study provides an exemplary basis for discussing the challenge of achieving social and environmental as well as economic domains of 'future sustainability'. The crucial supporting role of information and geospatial technologies in the Raintrust plan will also be discussed.

  1. Ontogenetic development of the nervus terminalis in toothed whales. Evidence for its non-olfactory nature.

    PubMed

    Buhl, E H; Oelschläger, H A

    1986-01-01

    For the first time in cetaceans, the development of the terminalis system and its continuity between the olfactory placode and the telencephalon has been demonstrated by light microscopy. In the early development of toothed whales (Odontoceti) this system is partially incorporated within the fila olfactoria which grow out from the olfactory placode. As the peripheral olfactory system is reduced in later stages, a strongly developed ganglionlike structure (terminalis ganglion) remains within the primitive meninx. Peripherally it is connected via the cribriform plate with ganglionic cell clusters near the septal mucosa. Centrally it is attached to the telencephalon (olfactory tubercle, septal region) by several nerve fibre bundles. In contrast to all other mammalian groups, toothed whales and dolphins are anosmatic while being totally adapted to aquatic life. Therefore the remaining ganglion and plexus must have non-olfactory properties. They may be responsible for the autonomic innervation of intracranial arteries and of the large mucous epithelia in the accessory nasal air sacs. The morphology, evolution and functional implications of the terminalis system in odontocetes and other mammals are discussed.

  2. A modular approach to creating large engineered cartilage surfaces.

    PubMed

    Ford, Audrey C; Chui, Wan Fung; Zeng, Anne Y; Nandy, Aditya; Liebenberg, Ellen; Carraro, Carlo; Kazakia, Galateia; Alliston, Tamara; O'Connell, Grace D

    2018-01-23

    Native articular cartilage has limited capacity to repair itself from focal defects or osteoarthritis. Tissue engineering has provided a promising biological treatment strategy that is currently being evaluated in clinical trials. However, current approaches in translating these techniques to developing large engineered tissues remains a significant challenge. In this study, we present a method for developing large-scale engineered cartilage surfaces through modular fabrication. Modular Engineered Tissue Surfaces (METS) uses the well-known, but largely under-utilized self-adhesion properties of de novo tissue to create large scaffolds with nutrient channels. Compressive mechanical properties were evaluated throughout METS specimens, and the tensile mechanical strength of the bonds between attached constructs was evaluated over time. Raman spectroscopy, biochemical assays, and histology were performed to investigate matrix distribution. Results showed that by Day 14, stable connections had formed between the constructs in the METS samples. By Day 21, bonds were robust enough to form a rigid sheet and continued to increase in size and strength over time. Compressive mechanical properties and glycosaminoglycan (GAG) content of METS and individual constructs increased significantly over time. The METS technique builds on established tissue engineering accomplishments of developing constructs with GAG composition and compressive properties approaching native cartilage. This study demonstrated that modular fabrication is a viable technique for creating large-scale engineered cartilage, which can be broadly applied to many tissue engineering applications and construct geometries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Scaling laws of passive-scalar diffusion in the interstellar medium

    NASA Astrophysics Data System (ADS)

    Colbrook, Matthew J.; Ma, Xiangcheng; Hopkins, Philip F.; Squire, Jonathan

    2017-05-01

    Passive-scalar mixing (metals, molecules, etc.) in the turbulent interstellar medium (ISM) is critical for abundance patterns of stars and clusters, galaxy and star formation, and cooling from the circumgalactic medium. However, the fundamental scaling laws remain poorly understood in the highly supersonic, magnetized, shearing regime relevant for the ISM. We therefore study the full scaling laws governing passive-scalar transport in idealized simulations of supersonic turbulence. Using simple phenomenological arguments for the variation of diffusivity with scale based on Richardson diffusion, we propose a simple fractional diffusion equation to describe the turbulent advection of an initial passive scalar distribution. These predictions agree well with the measurements from simulations, and vary with turbulent Mach number in the expected manner, remaining valid even in the presence of a large-scale shear flow (e.g. rotation in a galactic disc). The evolution of the scalar distribution is not the same as obtained using simple, constant 'effective diffusivity' as in Smagorinsky models, because the scale dependence of turbulent transport means an initially Gaussian distribution quickly develops highly non-Gaussian tails. We also emphasize that these are mean scalings that apply only to ensemble behaviours (assuming many different, random scalar injection sites): individual Lagrangian 'patches' remain coherent (poorly mixed) and simply advect for a large number of turbulent flow-crossing times.

  4. Pathogenesis of amyotrophic lateral sclerosis.

    PubMed

    Morgan, Sarah; Orrell, Richard W

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) or motor neuron disease is a rapidly progressive neurodegenerative disorder. The primary involvement is of motor neurons in the brain, spinal cord and peripherally. There is secondary weakness of muscles and primary involvement of other brain regions, especially involving cognition. Peer-reviewed journal articles and reviews. PubMed.gov The pathogenesis of ALS remains largely unknown. There are a wide range of potential mechanisms related to neurodegeneration. An increasing number of genetic factors are recognized. There remains controversy, or lack of knowledge, in explaining how cellular events manifest as the complex human disease. There is controversy as to how well cellular and animal models of disease relate to the human disease. Large-scale international collaborative genetic epidemiological studies are replacing local studies. Therapies related to pathogenesis remain elusive, with the greatest advances to date relating to provision of care (including multidisciplinary management) and supportive care (nutrition and respiratory support). The identification of C9orf72 hexanucleotide repeats as the most frequent genetic background to ALS, and the association with frontotemporal dementia, gives the potential of a genetic background against which to study other risk factors, triggers and pathogenic mechanisms, and to develop potential therapies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Wind and Wildlife in the Northern Great Plains: Identifying Low-Impact Areas for Wind Development

    PubMed Central

    Fargione, Joseph; Kiesecker, Joseph; Slaats, M. Jan; Olimb, Sarah

    2012-01-01

    Wind energy offers the potential to reduce carbon emissions while increasing energy independence and bolstering economic development. However, wind energy has a larger land footprint per Gigawatt (GW) than most other forms of energy production and has known and predicted adverse effects on wildlife. The Northern Great Plains (NGP) is home both to some of the world’s best wind resources and to remaining temperate grasslands, the most converted and least protected ecological system on the planet. Thus, appropriate siting and mitigation of wind development is particularly important in this region. Steering energy development to disturbed lands with low wildlife value rather than placing new developments within large and intact habitats would reduce impacts to wildlife. Goals for wind energy development in the NGP are roughly 30 GW of nameplate capacity by 2030. Our analyses demonstrate that there are large areas where wind development would likely have few additional impacts on wildlife. We estimate there are ∼1,056 GW of potential wind energy available across the NGP on areas likely to have low-impact for biodiversity, over 35 times development goals. New policies and approaches will be required to guide wind energy development to low-impact areas. PMID:22848505

  6. Wind and wildlife in the Northern Great Plains: identifying low-impact areas for wind development.

    PubMed

    Fargione, Joseph; Kiesecker, Joseph; Slaats, M Jan; Olimb, Sarah

    2012-01-01

    Wind energy offers the potential to reduce carbon emissions while increasing energy independence and bolstering economic development. However, wind energy has a larger land footprint per Gigawatt (GW) than most other forms of energy production and has known and predicted adverse effects on wildlife. The Northern Great Plains (NGP) is home both to some of the world's best wind resources and to remaining temperate grasslands, the most converted and least protected ecological system on the planet. Thus, appropriate siting and mitigation of wind development is particularly important in this region. Steering energy development to disturbed lands with low wildlife value rather than placing new developments within large and intact habitats would reduce impacts to wildlife. Goals for wind energy development in the NGP are roughly 30 GW of nameplate capacity by 2030. Our analyses demonstrate that there are large areas where wind development would likely have few additional impacts on wildlife. We estimate there are ∼1,056 GW of potential wind energy available across the NGP on areas likely to have low-impact for biodiversity, over 35 times development goals. New policies and approaches will be required to guide wind energy development to low-impact areas.

  7. Ethical Considerations for Clinical Trials in Inflammatory Bowel Disease

    PubMed Central

    Becker, Samuel; Siegler, Mark

    2014-01-01

    Although advancements in the field of inflammatory bowel disease (IBD) include effective therapies for many patients with Crohn’s disease and ulcerative colitis, there remains a large unmet need, and there is a large number of investigational agents in the pipeline. Drug development through clinical trials is critical to understanding the safety and efficacy of new therapies in the affected human population, and the need for ethical trial design is of the utmost importance. This paper explores the ethical issues of clinical trials in IBD, focusing on placebo-controlled trials, vulnerable patients, exposure to monoclonal antibodies, globalization of trials, and surgical advances. PMID:24799837

  8. Pitch sensation involves stochastic resonance

    PubMed Central

    Martignoli, Stefan; Gomez, Florian; Stoop, Ruedi

    2013-01-01

    Pitch is a complex hearing phenomenon that results from elicited and self-generated cochlear vibrations. Read-off vibrational information is relayed higher up the auditory pathway, where it is then condensed into pitch sensation. How this can adequately be described in terms of physics has largely remained an open question. We have developed a peripheral hearing system (in hardware and software) that reproduces with great accuracy all salient pitch features known from biophysical and psychoacoustic experiments. At the level of the auditory nerve, the system exploits stochastic resonance to achieve this performance, which may explain the large amount of noise observed in the working auditory nerve. PMID:24045830

  9. Results of an Institutional LGBT Climate Survey at an Academic Medical Center.

    PubMed

    Chester, Sean D; Ehrenfeld, Jesse M; Eckstrand, Kristen L

    2014-12-01

    The purpose of this study was to characterize the climate and culture experienced by lesbian, gay, bisexual, and transgender (LGBT) employees and students at one large academic medical center. An anonymous, online institutional climate survey was used to assess the attitudes and experiences of LGBT employees and students. There were 42 LGBT and 14 non-LGBT survey participants. Results revealed that a surprisingly large percentage of LGBT individuals experienced pressure to remain "closeted" and were harassed despite medical center policies of non-discrimination. Continuing training, inclusive policies and practices, and the development of mechanisms to address LGBT-specific harassment are necessary for improving institutional climate.

  10. Reverse engineering and analysis of large genome-scale gene networks

    PubMed Central

    Aluru, Maneesha; Zola, Jaroslaw; Nettleton, Dan; Aluru, Srinivas

    2013-01-01

    Reverse engineering the whole-genome networks of complex multicellular organisms continues to remain a challenge. While simpler models easily scale to large number of genes and gene expression datasets, more accurate models are compute intensive limiting their scale of applicability. To enable fast and accurate reconstruction of large networks, we developed Tool for Inferring Network of Genes (TINGe), a parallel mutual information (MI)-based program. The novel features of our approach include: (i) B-spline-based formulation for linear-time computation of MI, (ii) a novel algorithm for direct permutation testing and (iii) development of parallel algorithms to reduce run-time and facilitate construction of large networks. We assess the quality of our method by comparison with ARACNe (Algorithm for the Reconstruction of Accurate Cellular Networks) and GeneNet and demonstrate its unique capability by reverse engineering the whole-genome network of Arabidopsis thaliana from 3137 Affymetrix ATH1 GeneChips in just 9 min on a 1024-core cluster. We further report on the development of a new software Gene Network Analyzer (GeNA) for extracting context-specific subnetworks from a given set of seed genes. Using TINGe and GeNA, we performed analysis of 241 Arabidopsis AraCyc 8.0 pathways, and the results are made available through the web. PMID:23042249

  11. Passage of American shad: paradigms and realities

    USGS Publications Warehouse

    Haro, Alex; Castro-Santos, Theodore

    2012-01-01

    Despite more than 250 years of development, the passage of American shad Alosa sapidissima at dams and other barriers frequently remains problematic. Few improvements in design based on knowledge of the swimming, schooling, and migratory behaviors of American shad have been incorporated into passage structures. Large-scale technical fishways designed for the passage of adult salmonids on the Columbia River have been presumed to have good performance for American shad but have never been rigorously evaluated for this species. Similar but smaller fishway designs on the East Coast frequently have poor performance. Provision of effective downstream passage for both juvenile and postspawning adult American shad has been given little consideration in most passage projects. Ways to attract and guide American shad to both fishway entrances and downstream bypasses remain marginally understood. The historical development of passage structures for American shad has resulted in assumptions and paradigms about American shad behavior and passage that are frequently unsubstantiated by supporting data or appropriate experimentation. We propose that many of these assumptions and paradigms are either unfounded or invalid and that significant improvements to American shad upstream and downstream passage can be made via a sequential program of behavioral experimentation, application of experimental results to the physical and hydraulic design of new structures, and controlled tests of large-scale prototype structures in the laboratory and field.

  12. Refugee camps, fire disasters and burn injuries.

    PubMed

    Atiyeh, B S; Gunn, S W A

    2017-09-30

    In the past five years, no fewer than 15 conflicts have brought unspeakable tragedy and misery to millions across the world. At present, nearly 20 people are forcibly displaced every minute as a result of conflict or persecution, representing a crisis of historic proportions. Many displaced persons end up in camps generally developing in an impromptu fashion, and are totally dependent on humanitarian aid. The precarious condition of temporary installations puts the nearly 700 refugee camps worldwide at high risk of disease, child soldier and terrorist recruitment, and physical and sexual violence. Poorly planned, densely packed refugee settlements are also one of the most pathogenic environments possible, representing high risk for fires with potential for uncontrolled fire spread and development over sometimes quite large areas. Moreover, providing healthcare to refugees comes with its own unique challenges. Internationally recognized guidelines for minimum standards in shelters and settlements have been set, however they remain largely inapplicable. As for fire risk reduction, and despite the high number of fire incidents, it is not evident that fire safety can justify a higher priority. In that regard, a number of often conflicting influences will need to be considered. The greatest challenge remains in balancing the various risks, such as the need/cost of shelter against the fire risk/cost of fire protection.

  13. Refugee camps, fire disasters and burn injuries

    PubMed Central

    Atiyeh, B.S.; Gunn, S.W.A.

    2017-01-01

    Summary In the past five years, no fewer than 15 conflicts have brought unspeakable tragedy and misery to millions across the world. At present, nearly 20 people are forcibly displaced every minute as a result of conflict or persecution, representing a crisis of historic proportions. Many displaced persons end up in camps generally developing in an impromptu fashion, and are totally dependent on humanitarian aid. The precarious condition of temporary installations puts the nearly 700 refugee camps worldwide at high risk of disease, child soldier and terrorist recruitment, and physical and sexual violence. Poorly planned, densely packed refugee settlements are also one of the most pathogenic environments possible, representing high risk for fires with potential for uncontrolled fire spread and development over sometimes quite large areas. Moreover, providing healthcare to refugees comes with its own unique challenges. Internationally recognized guidelines for minimum standards in shelters and settlements have been set, however they remain largely inapplicable. As for fire risk reduction, and despite the high number of fire incidents, it is not evident that fire safety can justify a higher priority. In that regard, a number of often conflicting influences will need to be considered. The greatest challenge remains in balancing the various risks, such as the need/cost of shelter against the fire risk/cost of fire protection. PMID:29849526

  14. Mild Cognitive Impairment: Diagnosis, Longitudinal Course, and Emerging Treatments

    PubMed Central

    Vega, Jennifer N.; Newhouse, Paul A.

    2014-01-01

    Mild cognitive impairment (MCI) is widely regarded as the intermediate stage of cognitive impairment between the changes seen in normal cognitive aging and those associated with dementia. Elderly patients with MCI constitute a high-risk population for developing dementia, in particular Alzheimer’s disease (AD). Although the core clinical criteria for MCI have remained largely unchanged, the operational definition of MCI has undergone several revisions over the course of the last decade and remains an evolving diagnosis. Prognostic implications of this diagnosis are becoming clearer with regard to the risk of progressive cognitive deterioration. Although patients with MCI may represent an optimal target population for pharmacological and non-pharmacological interventions, results from clinical trials have been mixed and a definitive effective treatment remains elusive. This article provides a brief overview of the evolution of the concept of MCI and reviews current diagnostic criteria, the longitudinal course of the disorder, and current and emerging treatments for MCI. PMID:25160795

  15. Large-eddy simulation of a boundary layer with concave streamwise curvature

    NASA Technical Reports Server (NTRS)

    Lund, Thomas S.

    1994-01-01

    Turbulence modeling continues to be one of the most difficult problems in fluid mechanics. Existing prediction methods are well developed for certain classes of simple equilibrium flows, but are still not entirely satisfactory for a large category of complex non-equilibrium flows found in engineering practice. Direct and large-eddy simulation (LES) approaches have long been believed to have great potential for the accurate prediction of difficult turbulent flows, but the associated computational cost has been prohibitive for practical problems. This remains true for direct simulation but is no longer clear for large-eddy simulation. Advances in computer hardware, numerical methods, and subgrid-scale modeling have made it possible to conduct LES for flows or practical interest at Reynolds numbers in the range of laboratory experiments. The objective of this work is to apply ES and the dynamic subgrid-scale model to the flow of a boundary layer over a concave surface.

  16. Replica Exchange with Solute Tempering: Efficiency in Large Scale Systems

    PubMed Central

    Huang, Xuhui; Hagen, Morten; Kim, Byungchan; Friesner, Richard A.; Zhou, Ruhong; Berne, B. J.

    2009-01-01

    We apply the recently developed replica exchange with solute tempering (REST) to three large solvated peptide systems: an α-helix, a β-hairpin, and a TrpCage, with these peptides defined as the “central group”. We find that our original implementation of REST is not always more efficient than the replica exchange method (REM). Specifically, we find that exchanges between folded (F) and unfolded (U) conformations with vastly different structural energies are greatly reduced by the nonappearance of the water self-interaction energy in the replica exchange acceptance probabilities. REST, however, is expected to remain useful for a large class of systems for which the energy gap between the two states is not large, such as weakly bound protein–ligand complexes. Alternatively, a shell of water molecules can be incorporated into the central group, as discussed in the original paper. PMID:17439169

  17. Quantifying hyporheic exchange dynamics in a highly regulated large river reach.

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

    Hammond, Glenn Edward; Zhou, T; Huang, M

    Hyporheic exchange is an important mechanism taking place in riverbanks and riverbed sediments, where river water and shallow groundwater mix and interact with each other. The direction, magnitude, and residence time of the hyporheic flux that penetrates the river bed are critical for biogeochemical processes such as carbon and nitrogen cycling, and biodegradation of organic contaminants. Many approaches including field measurements and numerical methods have been developed to quantify the hyporheic exchanges in relatively small rivers. However, the spatial and temporal distributions of hyporheic exchanges in a large, regulated river reach remain less explored due to the large spatial domains,more » complexity of geomorphologic features and subsurface properties, and the great pressure gradient variations at the riverbed created by dam operations.« less

  18. The environmental-data automated track annotation (Env-DATA) system: linking animal tracks with environmental data

    USGS Publications Warehouse

    Dodge, Somayeh; Bohrer, Gil; Weinzierl, Rolf P.; Davidson, Sarah C.; Kays, Roland; Douglas, David C.; Cruz, Sebastian; Han, J.; Brandes, David; Wikelski, Martin

    2013-01-01

    The movement of animals is strongly influenced by external factors in their surrounding environment such as weather, habitat types, and human land use. With advances in positioning and sensor technologies, it is now possible to capture animal locations at high spatial and temporal granularities. Likewise, scientists have an increasing access to large volumes of environmental data. Environmental data are heterogeneous in source and format, and are usually obtained at different spatiotemporal scales than movement data. Indeed, there remain scientific and technical challenges in developing linkages between the growing collections of animal movement data and the large repositories of heterogeneous remote sensing observations, as well as in the developments of new statistical and computational methods for the analysis of movement in its environmental context. These challenges include retrieval, indexing, efficient storage, data integration, and analytical techniques.

  19. Highly Dynamic Host Actin Reorganization around Developing Plasmodium Inside Hepatocytes

    PubMed Central

    Gomes-Santos, Carina S. S.; Itoe, Maurice A.; Afonso, Cristina; Henriques, Ricardo; Gardner, Rui; Sepúlveda, Nuno; Simões, Pedro D.; Raquel, Helena; Almeida, António Paulo; Moita, Luis F.; Frischknecht, Friedrich; Mota, Maria M.

    2012-01-01

    Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver. PMID:22238609

  20. Health Consequences of the ‘Great Recession’ on the Employed: Evidence from an Industrial Cohort in Aluminum Manufacturing

    PubMed Central

    Modrek, Sepideh; Cullen, Mark R.

    2013-01-01

    While the negative effects of unemployment have been well studied, the consequences of layoffs and downsizing for those who remain employed are less well understood. This study used human resources and health claims data from a large multi-site fully insured aluminum company to explore the health consequences of downsizing on the remaining workforce. We exploit the variation in the timing and intensity of layoff to categorize 30 plants as high or low layoff plants. Next, we select a stably employed cohort of workers with history of health insurance going back to 2006 to 1) describe the selection process into layoff and 2) explore the association between the severity of plant level layoffs and the incidence of four chronic conditions in the remaining workforce. We examined four health outcomes: incident hypertension, diabetes, asthma/COPD and depression for a cohort of approximately 13,000 employees. Results suggest that there was an increased risk of developing hypertension for workers that remain at the plants with the highest level of layoffs, and increased risk of developing diabetes for salaried workers that remain at the plants with the highest level of layoffs. The hypertension results were robust to a several specification tests. In addition, the study design selected only healthy workers, therefore our results are likely to be a lower bound and suggest that adverse health consequences of the current recession may affect a broader proportion of the population than previously expected. PMID:23849284

  1. Leading Educational Change and Improvement at Scale: Some Inconvenient Truths about System Performance

    ERIC Educational Resources Information Center

    Harris, Alma; Jones, Michelle

    2017-01-01

    The challenges of securing educational change and transformation, at scale, remain considerable. While sustained progress has been made in some education systems (Fullan, 2009; Hargreaves & Shirley, 2009) generally, it remains the case that the pathway to large-scale, system improvement is far from easy or straightforward. While large-scale…

  2. Study of a High-Energy Upper Stage for Future Shuttle Missions

    NASA Technical Reports Server (NTRS)

    Dressler, Gordon A.; Matuszak, Leo W.; Stephenson, David D.

    2003-01-01

    Space Shuttle Orbiters are likely to remain in service to 2020 or beyond for servicing the International Space Station and for launching very high value spacecraft. There is a need for a new STS-deployable upper stage that can boost certain Orbiter payloads to higher energy orbits, up to and including Earth-escape trajectories. The inventory of solid rocket motor Inertial Upper Stages has been depleted, and it is unlikely that a LOX/LH2-fueled upper stage can fly on Shuttle due to safety concerns. This paper summarizes the results of a study that investigated a low cost, low risk approach to quickly developing a new large upper stage optimized to fly on the existing Shuttle fleet. Two design reference missions (DRMs) were specified: the James Webb Space Telescope (JWST) and the Space Interferometry Mission (SIM). Two categories of upper stage propellants were examined in detail: a storable liquid propellant and a storable gel propellant. Stage subsystems 'other than propulsion were based largely on heritage hardware to minimize cost, risk and development schedule span. The paper presents the ground rules and guidelines for conducting the study, the preliminary conceptual designs margins, assessments of technology readiness/risk, potential synergy with other programs, and preliminary estimates of development and production costs and schedule spans. Although the Orbiter Columbia was baselined for the study, discussion is provided to show how the results apply to the remaining STS Orbiter fleet.

  3. The future of fish passage science, engineering, and practice

    USGS Publications Warehouse

    Silva, Ana T.; Lucas, Martyn C.; Castro-Santos, Theodore R.; Katopodis, Christos; Baumgartner, Lee J.; Thiem, Jason D.; Aarestrup, Kim; Pompeu, Paulo S.; O'Brien, Gordon C.; Braun, Douglas C.; Burnett, Nicholas J.; Zhu, David Z.; Fjeldstad, Hans-Petter; Forseth, Torbjorn; Rajarathnam, Nallamuthu; Williams, John G.; Cooke, Steven J.

    2018-01-01

    Much effort has been devoted to developing, constructing and refining fish passage facilities to enable target species to pass barriers on fluvial systems, and yet, fishway science, engineering and practice remain imperfect. In this review, 17 experts from different fish passage research fields (i.e., biology, ecology, physiology, ecohydraulics, engineering) and from different continents (i.e., North and South America, Europe, Africa, Australia) identified knowledge gaps and provided a roadmap for research priorities and technical developments. Once dominated by an engineering‐focused approach, fishway science today involves a wide range of disciplines from fish behaviour to socioeconomics to complex modelling of passage prioritization options in river networks. River barrier impacts on fish migration and dispersal are currently better understood than historically, but basic ecological knowledge underpinning the need for effective fish passage in many regions of the world, including in biodiversity hotspots (e.g., equatorial Africa, South‐East Asia), remains largely unknown. Designing efficient fishways, with minimal passage delay and post‐passage impacts, requires adaptive management and continued innovation. While the use of fishways in river restoration demands a transition towards fish passage at the community scale, advances in selective fishways are also needed to manage invasive fish colonization. Because of the erroneous view in some literature and communities of practice that fish passage is largely a proven technology, improved international collaboration, information sharing, method standardization and multidisciplinary training are needed. Further development of regional expertise is needed in South America, Asia and Africa where hydropower dams are currently being planned and constructed.

  4. A new algorithm for construction of coarse-grained sites of large biomolecules.

    PubMed

    Li, Min; Zhang, John Z H; Xia, Fei

    2016-04-05

    The development of coarse-grained (CG) models for large biomolecules remains a challenge in multiscale simulations, including a rigorous definition of CG representations for them. In this work, we proposed a new stepwise optimization imposed with the boundary-constraint (SOBC) algorithm to construct the CG sites of large biomolecules, based on the s cheme of essential dynamics CG. By means of SOBC, we can rigorously derive the CG representations of biomolecules with less computational cost. The SOBC is particularly efficient for the CG definition of large systems with thousands of residues. The resulted CG sites can be parameterized as a CG model using the normal mode analysis based fluctuation matching method. Through normal mode analysis, the obtained modes of CG model can accurately reflect the functionally related slow motions of biomolecules. The SOBC algorithm can be used for the construction of CG sites of large biomolecules such as F-actin and for the study of mechanical properties of biomaterials. © 2015 Wiley Periodicals, Inc.

  5. A critical role for PDGFRα signaling in medial nasal process development.

    PubMed

    He, Fenglei; Soriano, Philippe

    2013-01-01

    The primitive face is composed of neural crest cell (NCC) derived prominences. The medial nasal processes (MNP) give rise to the upper lip and vomeronasal organ, and are essential for normal craniofacial development, but the mechanism of MNP development remains largely unknown. PDGFRα signaling is known to be critical for NCC development and craniofacial morphogenesis. In this study, we show that PDGFRα is required for MNP development by maintaining the migration of progenitor neural crest cells (NCCs) and the proliferation of MNP cells. Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRα function during MNP development. We thus establish PDGFRα as a novel regulator of MNP development and elucidate the roles of its downstream signaling pathways at cellular and molecular levels.

  6. The VLTI Roadmap

    NASA Astrophysics Data System (ADS)

    Mérand, A.

    2018-03-01

    ESO's Very Large Telescope Interferometer (VLTI) was a unique facility when it was conceived more than 30 years ago, and it remains competitive today in the field of milli-arcsecond angular resolution astronomy. Over the past decade, while the VLTI matured into an operationally efficient facility, it became limited by its first-generation instruments. As the second generation of VLTI instrumentation achieves first light, further developments for this unique facility are being planned and are described here.

  7. Late Holocene expansion of Ponderosa pine (Pinus ponderosa) in the Central Rocky Mountains, USA

    USGS Publications Warehouse

    Norris, Jodi R; Betancourt, Julio L.; Jackson, Stephen T.

    2016-01-01

    Main conclusions: P. ponderosa expanded its range across large parts of northern Wyoming and central Montana during the late Holocene, probably in response to both northward and westward increases in summer temperature and rainfall. The underlying climatic driver may be the same as for the contemporaneous expansion of J. osteosperma, but will remain undetermined without focused development and integration of independent palaeoclimate records in the region."

  8. Structural connectivity of the developing human amygdala.

    PubMed

    Saygin, Zeynep M; Osher, David E; Koldewyn, Kami; Martin, Rebecca E; Finn, Amy; Saxe, Rebecca; Gabrieli, John D E; Sheridan, Margaret

    2015-01-01

    A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus' connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age.

  9. Upper Palaeolithic ritualistic cannibalism at Gough's Cave (Somerset, UK): The human remains from head to toe.

    PubMed

    Bello, Silvia M; Saladié, Palmira; Cáceres, Isabel; Rodríguez-Hidalgo, Antonio; Parfitt, Simon A

    2015-05-01

    A recurring theme of late Upper Palaeolithic Magdalenian human bone assemblages is the remarkable rarity of primary burials and the common occurrence of highly-fragmentary human remains mixed with occupation waste at many sites. One of the most extensive Magdalenian human bone assemblages comes from Gough's Cave, a sizeable limestone cave set in Cheddar Gorge (Somerset), UK. After its discovery in the 1880s, the site was developed as a show cave and largely emptied of sediment, at times with minimal archaeological supervision. Some of the last surviving remnants of sediment within the cave were excavated between 1986 and 1992. The excavations uncovered intensively-processed human bones intermingled with abundant butchered large mammal remains and a diverse range of flint, bone, antler, and ivory artefacts. New ultrafiltrated radiocarbon determinations demonstrate that the Upper Palaeolithic human remains were deposited over a very short period of time, possibly during a series of seasonal occupations, about 14,700 years BP (before present). The human remains have been the subject of several taphonomic studies, culminating in a detailed reanalysis of the cranial remains that showed they had been carefully modified to make skull-cups. Our present analysis of the postcrania has identified a far greater degree of human modification than recorded in earlier studies. We identify extensive evidence for defleshing, disarticulation, chewing, crushing of spongy bone, and the cracking of bones to extract marrow. The presence of human tooth marks on many of the postcranial bones provides incontrovertible evidence for cannibalism. In a wider context, the treatment of the human corpses and the manufacture and use of skull-cups at Gough Cave have parallels with other Magdalenian sites in central and western Europe. This suggests that cannibalism during the Magdalenian was part of a customary mortuary practice that combined intensive processing and consumption of the bodies with ritual use of skull-cups. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. [Human remains in museums: research, preservation and communication. The experience of Turin University Museum of Anthropology and Etnography].

    PubMed

    Boano, Rosa; Grilletto, Renato; Rabino Massa, Emma

    2013-01-01

    The creation of large scientific collections has been an important development for anthropological and paleopathological research. Indeed the biological collections are irreplaceable reference systems for the biological reconstruction of past population. They also assume the important role of anthropological archives and, in the global description of man, permit the integration of historical data with those from bio-anthropolgical research. Thinking about the role of mummies and bones as scientific resources, best practice of preservation of ancient specimens should be of high priority for institution and researchers. By way of example, the authors mention their experience regarding ancient human remains preserved in the Museum of Anthropology and Ethnography at the University of Turin.

  11. Genetic causes of male infertility.

    PubMed

    Stouffs, Katrien; Seneca, Sara; Lissens, Willy

    2014-05-01

    Male infertility, affecting around half of the couples with a problem to get pregnant, is a very heterogeneous condition. Part of patients are having a defect in spermatogenesis of which the underlying causes (including genetic ones) remain largely unknown. The only genetic tests routinely used in the diagnosis of male infertility are the analyses for the presence of Yq microdeletions and/or chromosomal abnormalities. Various other single gene or polygenic defects have been proposed to be involved in male fertility. Yet, their causative effect often remains to be proven. The recent evolution in the development of whole genome-based techniques may help in clarifying the role of genes and other genetic factors involved in spermatogenesis and spermatogenesis defects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. World Health Organization's Mental Health Atlas 2005:implications for policy development

    PubMed Central

    SAXENA, SHEKHAR; SHARAN, PRATAP; GARRIDO, MARCO; SARACENO, BENEDETTO

    2006-01-01

    In 2005, the World Health Organization (WHO) launched the second edition of the Mental Health Atlas, consisting of revised and updated information on mental health from countries. The sources of information included the mental health focal points in the Ministries of Health, published literature and unpublished reports available to WHO. The results show that global mental health resources remain low and grossly inadequate to respond to the high level of need. In addition, the revised Atlas shows that the improvements over the period 2001 to 2004 are very small. Imbalances across income groups of countries remain largely the same. Enhancement in resources devoted to mental health is urgently needed, especially in low- and middle-income countries. PMID:17139355

  13. Development of an automated large-scale protein-crystallization and monitoring system for high-throughput protein-structure analyses.

    PubMed

    Hiraki, Masahiko; Kato, Ryuichi; Nagai, Minoru; Satoh, Tadashi; Hirano, Satoshi; Ihara, Kentaro; Kudo, Norio; Nagae, Masamichi; Kobayashi, Masanori; Inoue, Michio; Uejima, Tamami; Oda, Shunichiro; Chavas, Leonard M G; Akutsu, Masato; Yamada, Yusuke; Kawasaki, Masato; Matsugaki, Naohiro; Igarashi, Noriyuki; Suzuki, Mamoru; Wakatsuki, Soichi

    2006-09-01

    Protein crystallization remains one of the bottlenecks in crystallographic analysis of macromolecules. An automated large-scale protein-crystallization system named PXS has been developed consisting of the following subsystems, which proceed in parallel under unified control software: dispensing precipitants and protein solutions, sealing crystallization plates, carrying robot, incubators, observation system and image-storage server. A sitting-drop crystallization plate specialized for PXS has also been designed and developed. PXS can set up 7680 drops for vapour diffusion per hour, which includes time for replenishing supplies such as disposable tips and crystallization plates. Images of the crystallization drops are automatically recorded according to a preprogrammed schedule and can be viewed by users remotely using web-based browser software. A number of protein crystals were successfully produced and several protein structures could be determined directly from crystals grown by PXS. In other cases, X-ray quality crystals were obtained by further optimization by manual screening based on the conditions found by PXS.

  14. New strategy for drug discovery by large-scale association analysis of molecular networks of different species.

    PubMed

    Zhang, Bo; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Wu, Ziyin; Zhang, Wenjuan; Yang, Xiaoyan; Gong, Fukai; Li, Yuerong; Chen, Xiaoyu; Gao, Shuo; Chen, Xuetong; Li, Yan; Lu, Aiping; Wang, Yonghua

    2016-02-25

    The development of modern omics technology has not significantly improved the efficiency of drug development. Rather precise and targeted drug discovery remains unsolved. Here a large-scale cross-species molecular network association (CSMNA) approach for targeted drug screening from natural sources is presented. The algorithm integrates molecular network omics data from humans and 267 plants and microbes, establishing the biological relationships between them and extracting evolutionarily convergent chemicals. This technique allows the researcher to assess targeted drugs for specific human diseases based on specific plant or microbe pathways. In a perspective validation, connections between the plant Halliwell-Asada (HA) cycle and the human Nrf2-ARE pathway were verified and the manner by which the HA cycle molecules act on the human Nrf2-ARE pathway as antioxidants was determined. This shows the potential applicability of this approach in drug discovery. The current method integrates disparate evolutionary species into chemico-biologically coherent circuits, suggesting a new cross-species omics analysis strategy for rational drug development.

  15. An Evidence-Based Practical Approach to Pediatric Otolaryngology in the Developing World.

    PubMed

    Belcher, Ryan H; Molter, David W; Goudy, Steven L

    2018-06-01

    Despite humanitarian otolaryngology groups traveling in record numbers to resource-limited areas treating pediatric otolaryngology disease processes and training local providers, there remains a large burden of unmet needs. There is a meager amount of published information that comes from the developing world from an otolaryngology standpoint. As would be expected, the little information that does comes involves some of the most common pediatric otolaryngology diseases and surgical burdens including childhood hearing loss, otitis media, adenotonsillectomies, airway obstructions requiring tracheostomies, foreign body aspirations, and craniomaxillofacial surgeries, including cleft lip and palate. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The levonorgestrel-releasing intrauterine system: Safety, efficacy, and patient acceptability

    PubMed Central

    Beatty, Megan N; Blumenthal, Paul D

    2009-01-01

    The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective and acceptable form of contraception used by over 150 million women worldwide. It also has a variety of noncontraceptive benefits including treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The LNG-IUS has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy. Overall, the system is very well tolerated and patient satisfaction is quite high when proper education regarding possible side effects is provided. However, despite all of the obvious benefits of the LNG-IUS, utilization rates remain quite low in the developed countries, especially in the United States. This is thought to be largely secondary to the persistent negative impressions from the Dalkon Shield intrauterine experience in the 1970s. This history continues to negatively influence the opinions of both patients and health care providers with regards to intrauterine devices. Providers should resolve to educate themselves and their patients on the current indications and uses for this device, as it, and intrauterine contraception in general, remains a largely underutilized approach to a variety of women’s health issues. PMID:19707273

  17. Nonconsumptive Effects of Predatory Chrysomya rufifacies (Diptera: Calliphoridae) Larval Cues on Larval Cochliomyia macellaria (Diptera: Calliphoridae) Growth and Development.

    PubMed

    Flores, Micah; Crippen, Tawni L; Longnecker, Michael; Tomberlin, Jeffery K

    2017-09-01

    Forensic entomologists often rely on development data associated with a given species to estimate when it colonized human or other vertebrate remains. In most instances, these development studies are based on single species reared in isolation in the laboratory. This study examined the impact of excretions and secretions (ES) associated with third-instar Chrysomya rufifacies (Macquart), a predator, on the development of its prey, Cochliomyia macellaria (F.). Not surprisingly, Ch. rufifacies ES did not impact the development of first- or second-instar C. macellaria, which are typically not preyed on by Ch. rufifacies. However, development of third-instar C. macellaria, which do experience predation, was impacted. First, larvae were longer than those in the control (deionized water, dH2O). Filtering the ES and removing the associated bacteria and byproducts >0.2 µm dampened the previous impact observed by the unfiltered ES on third-instar C. macellaria. Second, third-instar C. macellaria treated with unfiltered ES completed pupariation 8 h quicker than the controls. Filtering the ES lessened this effect by 50%. And finally, third-instar C. macellaria treated with filtered or unfiltered Ch. rufifacies ES reached adulthood ∼5 h faster than controls treated with dH2O. In summary, these data have large ramifications for forensic entomology, as multiple species being present on decomposing remains is not uncommon. Understanding the impact of associated ES produced by interspecific cohorts on associated development could lead to more precise estimates of the minimum postmortem interval for forensic investigation of decomposing remains. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Mid-Neolithic Exploitation of Mollusks in the Guanzhong Basin of Northwestern China: Preliminary Results

    PubMed Central

    Li, Fengjiang; Wu, Naiqin; Lu, Houyuan; Zhang, Jianping; Wang, Weilin; Ma, Mingzhi; Zhang, Xiaohu; Yang, Xiaoyan

    2013-01-01

    Mollusk remains are abundant in archaeological sites in the Guanzhong Basin of Northwestern China, providing good opportunities for investigations into the use of mollusks by prehistoric humans. Here we report on freshwater gastropod and bivalve mollusks covering the time interval from about 5600 to 4500 cal. yrs BP from sites of Mid-Late Neolithic age. They are identified as Cipangopaludina chinensis and Unio douglasiae, both of which are currently food for humans. The shells are well preserved and have no signs of abrasion. They are all freshwater gastropods and bivalves found in pits without water-reworked deposits and have modern representatives which can be observed in rivers, reservoirs, and paddy fields in the studied region. Mollusk shells were frequently recovered in association with mammal bones, lithic artifacts, and pottery. These lines of evidence indicate that the mollusks are the remains of prehistoric meals. The mollusk shells were likely discarded into the pits by prehistoric humans after the flesh was eaten. However, these mollusk remains may not have been staple food since they are not found in large quantities. Mollusk shell tools and ornaments are also observed. Shell tools include shell knives, shell reaphooks and arrowheads, whereas shell ornaments are composed of pendants and loops. All the shell tools and ornaments are made of bivalve mollusks and do not occur in large numbers. The finding of these freshwater mollusk remains supports the view that the middle Holocene climate in the Guanzhong Basin may have been warm and moist, which was probably favorable to freshwater mollusks growing and developing in the region. PMID:23544050

  19. Visualizing the molecular sociology at the HeLa cell nuclear periphery.

    PubMed

    Mahamid, Julia; Pfeffer, Stefan; Schaffer, Miroslava; Villa, Elizabeth; Danev, Radostin; Cuellar, Luis Kuhn; Förster, Friedrich; Hyman, Anthony A; Plitzko, Jürgen M; Baumeister, Wolfgang

    2016-02-26

    The molecular organization of eukaryotic nuclear volumes remains largely unexplored. Here we combined recent developments in cryo-electron tomography (cryo-ET) to produce three-dimensional snapshots of the HeLa cell nuclear periphery. Subtomogram averaging and classification of ribosomes revealed the native structure and organization of the cytoplasmic translation machinery. Analysis of a large dynamic structure-the nuclear pore complex-revealed variations detectable at the level of individual complexes. Cryo-ET was used to visualize previously elusive structures, such as nucleosome chains and the filaments of the nuclear lamina, in situ. Elucidation of the lamina structure provides insight into its contribution to metazoan nuclear stiffness. Copyright © 2016, American Association for the Advancement of Science.

  20. The USC Epigenome Center.

    PubMed

    Laird, Peter W

    2009-10-01

    The University of Southern California (USC, CA, USA) has a long tradition of excellence in epigenetics. With the recent explosive growth and technological maturation of the field of epigenetics, it became clear that a dedicated high-throughput epigenomic data production facility would be needed to remain at the forefront of epigenetic research. To address this need, USC launched the USC Epigenome Center as the first large-scale center in academics dedicated to epigenomic research. The Center is providing high-throughput data production for large-scale genomic and epigenomic studies, and developing novel analysis tools for epigenomic research. This unique facility promises to be a valuable resource for multidisciplinary research, education and training in genomics, epigenomics, bioinformatics, and translational medicine.

  1. Impacts of urbanization and agricultural development on observed changes in surface air temperature over mainland China from 1961 to 2006

    NASA Astrophysics Data System (ADS)

    Han, Songjun; Tang, Qiuhong; Xu, Di; Yang, Zhiyong

    2018-03-01

    A large proportion of meteorological stations in mainland China are located in or near either urban or agricultural lands that were established throughout the period of rapid urbanization and agricultural development (1961-2006). The extent of the impacts of urbanization and agricultural development on observed air temperature changes across different climate regions remains elusive. This study evaluates the surface air temperature trends observed by 598 meteorological stations in relation to the urbanization and agricultural development over the arid northwest, semi-arid intermediate, and humid southeast regions of mainland China based on linear regressions of temperature trends on the fractions of urban and cultivated land within a 3-km radius of the stations. In all three regions, the stations surrounded by large urban land tend to experience rapid warming, especially at minimum temperature. This dependence is particularly significant in the southeast region, which experiences the most intense urbanization. In the northwest and intermediate regions, stations surrounded by large cultivated land encounter less warming during the main growing season, especially at the maximum temperature changes. These findings suggest that the observed surface warming has been affected by urbanization and agricultural development represented by urban and cultivated land fractions around stations in with land cover changes in their proximity and should thus be considered when analyzing regional temperature changes in mainland China.

  2. Sustaining Community Participation: What Remains After the Money Ends?

    NASA Astrophysics Data System (ADS)

    Nkansa, Grace Akukwe; Chapman, David W.

    2006-12-01

    SUSTAINING COMMUNITY PARTICIPATION: WHAT REMAINS AFTER THE MONEY ENDS? - A major concern confronting development specialists in the education sector is the sustainability of project activities and outcomes, that is, their ability to persist once external funding ends. The increased attention of international development-assistance organizations to sustainability reflects the greater recent focus on outcome-based funding. The present study investigates differences between six communities in Ghana that varied in their ability to sustain externally initiated community-participation activities beyond the life of the external development-assistance project that promoted those activities. It was hypothesized that high- and low-sustaining communities differ in eight managerial and socio-cultural dimensions suggested by earlier research to be important for sustainability of community-level activities: planning, transparency, leadership, and participation, on one hand, and, on the other, social cohesion, resources, community skills, and valuing of education. Findings indicate that leadership and social cohesion are the two most vital elements in the sustainability of organizational structures intended to promote community participation in the oversight of local schools. Other factors suggested by the model are largely subsumed under leadership, so that the model can be simplified.

  3. Ubiquitinated Proteome: Ready for Global?*

    PubMed Central

    Shi, Yi; Xu, Ping; Qin, Jun

    2011-01-01

    Ubiquitin (Ub) is a small and highly conserved protein that can covalently modify protein substrates. Ubiquitination is one of the major post-translational modifications that regulate a broad spectrum of cellular functions. The advancement of mass spectrometers as well as the development of new affinity purification tools has greatly expedited proteome-wide analysis of several post-translational modifications (e.g. phosphorylation, glycosylation, and acetylation). In contrast, large-scale profiling of lysine ubiquitination remains a challenge. Most recently, new Ub affinity reagents such as Ub remnant antibody and tandem Ub binding domains have been developed, allowing for relatively large-scale detection of several hundreds of lysine ubiquitination events in human cells. Here we review different strategies for the identification of ubiquitination site and discuss several issues associated with data analysis. We suggest that careful interpretation and orthogonal confirmation of MS spectra is necessary to minimize false positive assignments by automatic searching algorithms. PMID:21339389

  4. CPU architecture for a fast and energy-saving calculation of convolution neural networks

    NASA Astrophysics Data System (ADS)

    Knoll, Florian J.; Grelcke, Michael; Czymmek, Vitali; Holtorf, Tim; Hussmann, Stephan

    2017-06-01

    One of the most difficult problem in the use of artificial neural networks is the computational capacity. Although large search engine companies own specially developed hardware to provide the necessary computing power, for the conventional user only remains the state of the art method, which is the use of a graphic processing unit (GPU) as a computational basis. Although these processors are well suited for large matrix computations, they need massive energy. Therefore a new processor on the basis of a field programmable gate array (FPGA) has been developed and is optimized for the application of deep learning. This processor is presented in this paper. The processor can be adapted for a particular application (in this paper to an organic farming application). The power consumption is only a fraction of a GPU application and should therefore be well suited for energy-saving applications.

  5. Do faults trigger folding in the lithosphere?

    NASA Astrophysics Data System (ADS)

    Gerbault, Muriel; Burov, Eugenii B.; Poliakov, Alexei N. B.; Daignières, Marc

    A number of observations reveal large periodic undulations within the oceanic and continental lithospheres. The question if these observations are the result of large-scale compressive instabilities, i.e. buckling, remains open. In this study, we support the buckling hypothesis by direct numerical modeling. We compare our results with the data on three most proeminent cases of the oceanic and continental folding-like deformation (Indian Ocean, Western Gobi (Central Asia) and Central Australia). We demonstrate that under reasonable tectonic stresses, folds can develop from brittle faults cutting through the brittle parts of a lithosphere. The predicted wavelengths and finite growth rates are in agreement with observations. We also show that within a continental lithosphere with thermal age greater than 400 My, either a bi-harmonic mode (two superimposed wavelengths, crustal and mantle one) or a coupled mode (mono-layer deformation) of inelastic folding can develop, depending on the strength and thickness of the lower crust.

  6. Occupational exposure to municipal solid wastes and development of toxic neuropathies: possible role of nutrient supplementation, complementary and alternative medicines in chemoprevention.

    PubMed

    Ekor, Martins; Odewabi, Adesina O

    2014-09-01

    Achieving effective municipal solid waste (MSW) management remains a major challenge and waste generation and accumulation continue to constitute important environmental and public health concern, particularly in most developing countries. Although the general population is at risk of adverse health consequences and hazards associated with exposure to MSW, the waste management workers (WMWs) are the most vulnerable because of their direct involvement in the disposal of waste, with increasing evidence of work-related health and safety risks among these individuals. Among the numerous work-related health hazards prevalent in WMWs, development of toxic neuropathies following chronic occupational exposure remains poorly recognized. However, the risk or predisposition to toxic neuropathies is becoming evident considering the increasing recognition of large amount of neurotoxic heavy metals and hazardous industrial materials present in MSW in most parts of the world. The present review seeks to draw attention to the continuous vulnerability of the WMWs to developing toxic neuropathies. This is aimed at facilitating conscious efforts by relevant governmental and nongovernmental agencies towards promoting risk reduction and ensuring adequate protection against possible toxic polyneuropathies associated with occupational exposure to solid wastes. While continuous education of the WMWs on the need for adequate compliance to safety regulations and practice remains sacrosanct towards achieving significant reduction in toxic neuropathies and related adverse health consequences of waste handling, it is also our intention in this review to underscore the possible relevance of nutrient supplementation and alternative medicines in chemoprevention.

  7. Ultrastructural and structural characterization of zygotes and embryos during development in Sargassum cymosum (Phaeophyceae, Fucales).

    PubMed

    Rover, Ticiane; Simioni, Carmen; Hable, Whitney; Bouzon, Zenilda L

    2015-03-01

    This study investigates the pattern and performance of cellular structures during the early development of zygotes and embryos of Sargassum cymosum. The early development S. cymosum germlings has already been characterized and compared with the pattern of development established for all fucoid algae, in which the zygote remains attached to the receptacle by mucilage during the establishment of polarity and early cell division. As in the algae Fucus and Silvetia, the first division is transverse across the longer axis of the zygote of S. cymosum. However, the cell that will give rise to the rhizoids is not determined in the first division; rather, the formation of this cell occurs with the second division, forming a small cell in the embryo shaded site. Stabilizing polarity during the process of forming a multicellular embryo occurs rapidly. During development, significant cytoplasmic alterations take place. Initially, the cytoplasm shows large clusters of phenolic compounds located in specific parts, but later, in the course of development, these compounds are dispersed in the cytoplasm, although a significant amount remains confined to the nucleus. Moreover, to produce more zygotes and higher growth rates for the germlings, the best conditions found for the species S. cymosum were 22 and 26 °C, respectively.

  8. Flower development: open questions and future directions.

    PubMed

    Wellmer, Frank; Bowman, John L; Davies, Brendan; Ferrándiz, Cristina; Fletcher, Jennifer C; Franks, Robert G; Graciet, Emmanuelle; Gregis, Veronica; Ito, Toshiro; Jack, Thomas P; Jiao, Yuling; Kater, Martin M; Ma, Hong; Meyerowitz, Elliot M; Prunet, Nathanaël; Riechmann, José Luis

    2014-01-01

    Almost three decades of genetic and molecular analyses have resulted in detailed insights into many of the processes that take place during flower development and in the identification of a large number of key regulatory genes that control these processes. Despite this impressive progress, many questions about how flower development is controlled in different angiosperm species remain unanswered. In this chapter, we discuss some of these open questions and the experimental strategies with which they could be addressed. Specifically, we focus on the areas of floral meristem development and patterning, floral organ specification and differentiation, as well as on the molecular mechanisms underlying the evolutionary changes that have led to the astounding variations in flower size and architecture among extant and extinct angiosperms.

  9. Towards Development of Clustering Applications for Large-Scale Comparative Genotyping and Kinship Analysis Using Y-Short Tandem Repeats.

    PubMed

    Seman, Ali; Sapawi, Azizian Mohd; Salleh, Mohd Zaki

    2015-06-01

    Y-chromosome short tandem repeats (Y-STRs) are genetic markers with practical applications in human identification. However, where mass identification is required (e.g., in the aftermath of disasters with significant fatalities), the efficiency of the process could be improved with new statistical approaches. Clustering applications are relatively new tools for large-scale comparative genotyping, and the k-Approximate Modal Haplotype (k-AMH), an efficient algorithm for clustering large-scale Y-STR data, represents a promising method for developing these tools. In this study we improved the k-AMH and produced three new algorithms: the Nk-AMH I (including a new initial cluster center selection), the Nk-AMH II (including a new dominant weighting value), and the Nk-AMH III (combining I and II). The Nk-AMH III was the superior algorithm, with mean clustering accuracy that increased in four out of six datasets and remained at 100% in the other two. Additionally, the Nk-AMH III achieved a 2% higher overall mean clustering accuracy score than the k-AMH, as well as optimal accuracy for all datasets (0.84-1.00). With inclusion of the two new methods, the Nk-AMH III produced an optimal solution for clustering Y-STR data; thus, the algorithm has potential for further development towards fully automatic clustering of any large-scale genotypic data.

  10. "First generation" automated DNA sequencing technology.

    PubMed

    Slatko, Barton E; Kieleczawa, Jan; Ju, Jingyue; Gardner, Andrew F; Hendrickson, Cynthia L; Ausubel, Frederick M

    2011-10-01

    Beginning in the 1980s, automation of DNA sequencing has greatly increased throughput, reduced costs, and enabled large projects to be completed more easily. The development of automation technology paralleled the development of other aspects of DNA sequencing: better enzymes and chemistry, separation and imaging technology, sequencing protocols, robotics, and computational advancements (including base-calling algorithms with quality scores, database developments, and sequence analysis programs). Despite the emergence of high-throughput sequencing platforms, automated Sanger sequencing technology remains useful for many applications. This unit provides background and a description of the "First-Generation" automated DNA sequencing technology. It also includes protocols for using the current Applied Biosystems (ABI) automated DNA sequencing machines. © 2011 by John Wiley & Sons, Inc.

  11. Counselling for HIV infection and AIDS: the past and the future.

    PubMed

    Green, J

    1989-01-01

    The history of counselling in HIV infection and AIDS is reviewed and the stages in the development of the area are set out. The way in which the area has developed in the West is related to local circumstances and the need for the development of models suited to local circumstances elsewhere in the world is stressed. There are many areas of of HIV/AIDS counselling where considerable uncertainty about the right approach remains, for instance with injecting drug users and with HIV-infected pregnant women. There is a great and largely unmet need for further research in the area and some of the questions which need to be addressed are set out.

  12. Rethinking the early history of post-Vygotskian psychology: the case of the Kharkov school.

    PubMed

    Yasnitsky, Anton; Ferrari, Michel

    2008-05-01

    Between the death of Vygotsky in 1934 and the discovery of Vygotsky's work in the West in 1962, Vygotskian psychology was developed through research done by the first generation of Vygotsky's students and their followers, primarily associated with the Kharkov School. Surprisingly, these studies carried out in the 1930s, of great importance for the development of virtually all subsequent Vygotskian psychology, still remain largely unknown; this represents a significant gap in understanding the history of Vygotskian psychology as an empirical study of consciousness. This paper provides a systematic overview of the research agenda of the Kharkov group between 1931 and 1941 and provides new insights into the early development of Vygotskian psychology.

  13. Active space debris removal by using laser propulsion

    NASA Astrophysics Data System (ADS)

    Rezunkov, Yu. A.

    2013-03-01

    At present, a few projects on the space debris removal by using highpower lasers are developed. One of the established projects is the ORION proposed by Claude Phipps from Photonics Associates Company and supported by NASA (USA) [1]. But the technical feasibility of the concept is limited by sizes of the debris objects (from 1 to 10 cm) because of a small thrust impulse generated at the laser ablation of the debris materials. At the same time, the removal of rocket upper stages and satellites, which have reached the end of their lives, has been carried out only in a very small number of cases and most of them remain on the Low Earth Orbits (LEO). To reduce the amount of these large-size objects, designing of space systems allowing deorbiting upper rocket stages and removing large-size satellite remnants from economically and scientifically useful orbits to disposal ones is considered. The suggested system is based on high-power laser propulsion. Laser-Orbital Transfer Vehicle (LOTV) with the developed aerospace laser propulsion engine is considered as applied to the problem of mitigation of man-made large-size space debris in LEO.

  14. Annual Research Briefs: 1995

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This report contains the 1995 annual progress reports of the Research Fellows and students of the Center for Turbulence Research (CTR). In 1995 CTR continued its concentration on the development and application of large-eddy simulation to complex flows, development of novel modeling concepts for engineering computations in the Reynolds averaged framework, and turbulent combustion. In large-eddy simulation, a number of numerical and experimental issues have surfaced which are being addressed. The first group of reports in this volume are on large-eddy simulation. A key finding in this area was the revelation of possibly significant numerical errors that may overwhelm the effects of the subgrid-scale model. We also commissioned a new experiment to support the LES validation studies. The remaining articles in this report are concerned with Reynolds averaged modeling, studies of turbulence physics and flow generated sound, combustion, and simulation techniques. Fundamental studies of turbulent combustion using direct numerical simulations which started at CTR will continue to be emphasized. These studies and their counterparts carried out during the summer programs have had a noticeable impact on combustion research world wide.

  15. Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points

    PubMed Central

    Pittman, Andrew J.; Law, Mei-Yee; Chien, Chi-Bin

    2008-01-01

    Summary Navigating axons respond to environmental guidance signals, but can also follow axons that have gone before—pioneer axons. Pioneers have been studied extensively in simple systems, but the role of axon-axon interactions remains largely unexplored in large vertebrate axon tracts, where cohorts of identical axons could potentially use isotypic interactions to guide each other through multiple choice points. Furthermore, the relative importance of axon-axon interactions compared to axon-autonomous receptor function has not been assessed. Here we test the role of axon-axon interactions in retinotectal development, by devising a technique to selectively remove or replace early-born retinal ganglion cells (RGCs). We find that early RGCs are both necessary and sufficient for later axons to exit the eye. Furthermore, introducing misrouted axons by transplantation reveals that guidance from eye to tectum relies heavily on interactions between axons, including both pioneer-follower and community effects. We conclude that axon-axon interactions and ligand-receptor signaling have coequal roles, cooperating to ensure the fidelity of axon guidance in developing vertebrate tracts. PMID:18653554

  16. Health Economics at the Crossroads of Centuries – From the Past to the Future

    PubMed Central

    Jakovljevic, Mihajlo (Michael); Ogura, Seiritsu

    2016-01-01

    Health economics, as an interdisciplinary science, has experienced exceptionally bold evolution through the past eight decades. Generations of committed scholars have built up huge body of knowledge and developed a set of methodological tools to assist health-care authorities with resource allocation process. Following its conception at the US National Bureau of Economic Research and Ivy League US Universities, this science has spread across the Globe. It has adapted to a myriad of local conditions and needs of the national health systems with diverse historical legacies, medical services provision, and financing patterns. Challenge of financial sustainability facing modern day health systems remains primarily attributable to population aging, prosperity diseases, large scale migrations, rapid urbanization, and technological innovation in medicine. Despite promising developments in developing countries with emerging BRICS markets on the lead, rising out-of-pocket health spending continues to threaten affordability of medical care. Universal health coverage extension will likely remain serious challenge even for some of the most advanced OECD nations. These complex circumstances create strong drivers for inevitable further development of health economics. We believe that this interdisciplinary health science shall leave long-lasting blue print to be visible for decades to come. PMID:27376055

  17. Health Economics at the Crossroads of Centuries - From the Past to the Future.

    PubMed

    Jakovljevic, Mihajlo Michael; Ogura, Seiritsu

    2016-01-01

    Health economics, as an interdisciplinary science, has experienced exceptionally bold evolution through the past eight decades. Generations of committed scholars have built up huge body of knowledge and developed a set of methodological tools to assist health-care authorities with resource allocation process. Following its conception at the US National Bureau of Economic Research and Ivy League US Universities, this science has spread across the Globe. It has adapted to a myriad of local conditions and needs of the national health systems with diverse historical legacies, medical services provision, and financing patterns. Challenge of financial sustainability facing modern day health systems remains primarily attributable to population aging, prosperity diseases, large scale migrations, rapid urbanization, and technological innovation in medicine. Despite promising developments in developing countries with emerging BRICS markets on the lead, rising out-of-pocket health spending continues to threaten affordability of medical care. Universal health coverage extension will likely remain serious challenge even for some of the most advanced OECD nations. These complex circumstances create strong drivers for inevitable further development of health economics. We believe that this interdisciplinary health science shall leave long-lasting blue print to be visible for decades to come.

  18. Geneva-Seattle collaboration in support of developing country vaccine manufacturing.

    PubMed

    Stevenson, Michael A

    2018-04-01

    Vaccines were once produced almost exclusively by state-supported entities. While they remain essential tools for public health protection, the majority of the world's governments have allowed industry to assume responsibility for this function. This is significant because while the international harmonisation of quality assurance standards have effectively increased vaccine safety, they have also reduced the number of developing country vaccine producers, and Northern multinational pharmaceutical companies have shown little interest in offering the range of low-priced products needed in low and middle-income-country contexts. This article examines how public-private collaboration is relevant to contemporary efforts aimed at strengthening developing country manufacturers' capacity to produce high-quality, low-priced vaccines. Specifically, it casts light on the important and largely complimentary roles of the World Health Organization, The Bill and Melinda Gates Foundation, and the Seattle-based non-profit PATH, in this process. The take away message is that external support remains critical to ensuring that developing country vaccine manufacturers have the tools needed to produce for both domestic and global markets, and the United Nations supply chain, and collaboration at the public-private interface is driving organisational innovation focused on meeting these goals.

  19. Metals Additive Manufacturing. Great Promise in Mitigating Shortages but Some Risks Remain

    DTIC Science & Technology

    2016-11-01

    manufac- tured, shrinking development and delivery cycle times, and yielding improved performance at a lower cost per part. Shapes previously not...make a part. As illustrated in Figure 1, after each pass, a new layer of powder is laid down using a recoater blade and the process continues until...suggested deliberately abandon- ing large production runs and stockpiled inventories. The Defense Logistics Agency (DLA) lists AM as a priority in its R

  20. Building little safe and civilized communities: community crime prevention with Chinese characteristics?

    PubMed

    Zhong, Lena Y; Broadhurst, Roderic G

    2007-02-01

    This article describes a community crime prevention program in China, set against a background of rapid economic development, large internal population migration, and increasing crime rates. Traditional social control in China has been transformed to adapt to the new reform era, yet some mechanisms remain intact. Crime prevention measures and strategies resemble those adopted in the West; however, the differences, constituting the so-called Chinese characteristics with community crime prevention are significant.

  1. Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening

    NASA Astrophysics Data System (ADS)

    Hu, Xin; Legler, Patricia M.; Southall, Noel; Maloney, David J.; Simeonov, Anton; Jadhav, Ajit

    2014-07-01

    Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

  2. Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening.

    PubMed

    Hu, Xin; Legler, Patricia M; Southall, Noel; Maloney, David J; Simeonov, Anton; Jadhav, Ajit

    2014-07-01

    Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

  3. Issues for bringing digital libraries into public use

    NASA Technical Reports Server (NTRS)

    Flater, David W.; Yesha, Yelena

    1993-01-01

    In much the same way that the field of artificial intelligence produced a cult which fervently believed that computers would soon think like human beings, the existence of electronic books has resurrected the paperless society as a utopian vision to some, an apocalyptic horror to others. In this essay we have attempted to provide realistic notions of what digital libraries are likely to become if they are a popular success. E-books are capable of subsuming most of the media we use today and have the potential for added functionality by being interactive. The environmental impact of having millions more computers will be offset to some degree, perhaps even exceeded, by the fact that televisions, stereos, VCR's, CD players, newspapers, magazines, and books will become part of the computer system or be made redundant. On the whole, large-scale use of digital libraries is likely to be a winning proposition. Whether or not this comes to pass depends on the directions taken by today's researchers and software developers. By involving the public, the effort being put into digital libraries can be leveraged into something which is big enough to make a real change for the better. If digital libraries remain the exclusive property of government, universities, and large research firms, then large parts of the world will remain without digital libraries for years to come, just as they have remained without digital phone service for far too long. If software companies try to scuttle the project by patenting crucial algorithms and using proprietary data formats, all of us will suffer. Let us reverse the errors of the past and create a truly open digital library system.

  4. Global fishery development patterns are driven by profit but not trophic level.

    PubMed

    Sethi, Suresh A; Branch, Trevor A; Watson, Reg

    2010-07-06

    Successful ocean management needs to consider not only fishing impacts but drivers of harvest. Consolidating post-1950 global catch and economic data, we assess which attributes of fisheries are good indicators for fishery development. Surprisingly, year of development and economic value are not correlated with fishery trophic levels. Instead, patterns emerge of profit-driven fishing for attributes related to costs and revenues. Post-1950 fisheries initially developed on shallow ranging species with large catch, high price, and big body size, and then expanded to less desirable species. Revenues expected from developed fisheries declined 95% from 1951 to 1999, and few high catch or valuable fishing opportunities remain. These results highlight the importance of economic attributes of species as leading indicators for harvest-related impacts in ocean ecosystems.

  5. Global fishery development patterns are driven by profit but not trophic level

    PubMed Central

    Sethi, Suresh A.; Branch, Trevor A.; Watson, Reg

    2010-01-01

    Successful ocean management needs to consider not only fishing impacts but drivers of harvest. Consolidating post-1950 global catch and economic data, we assess which attributes of fisheries are good indicators for fishery development. Surprisingly, year of development and economic value are not correlated with fishery trophic levels. Instead, patterns emerge of profit-driven fishing for attributes related to costs and revenues. Post-1950 fisheries initially developed on shallow ranging species with large catch, high price, and big body size, and then expanded to less desirable species. Revenues expected from developed fisheries declined 95% from 1951 to 1999, and few high catch or valuable fishing opportunities remain. These results highlight the importance of economic attributes of species as leading indicators for harvest-related impacts in ocean ecosystems. PMID:20566867

  6. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours

    PubMed Central

    Perlman, Elizabeth J.; Gadd, Samantha; Arold, Stefan T.; Radhakrishnan, Anand; Gerhard, Daniela S.; Jennings, Lawrence; Huff, Vicki; Guidry Auvil, Jaime M.; Davidsen, Tanja M.; Dome, Jeffrey S.; Meerzaman, Daoud; Hsu, Chih Hao; Nguyen, Cu; Anderson, James; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Gastier-Foster, Julie M.; Ross, Nicole; Smith, Malcolm A.

    2015-01-01

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour. PMID:26635203

  7. Hydropower and sustainability: resilience and vulnerability in China's powersheds.

    PubMed

    McNally, Amy; Magee, Darrin; Wolf, Aaron T

    2009-07-01

    Large dams represent a whole complex of social, economic and ecological processes, perhaps more than any other large infrastructure project. Today, countries with rapidly developing economies are constructing new dams to provide energy and flood control to growing populations in riparian and distant urban communities. If the system is lacking institutional capacity to absorb these physical and institutional changes there is potential for conflict, thereby threatening human security. In this paper, we propose analyzing sustainability (political, socioeconomic, and ecological) in terms of resilience versus vulnerability, framed within the spatial abstraction of a powershed. The powershed framework facilitates multi-scalar and transboundary analysis while remaining focused on the questions of resilience and vulnerability relating to hydropower dams. Focusing on examples from China, this paper describes the complex nature of dams using the sustainability and powershed frameworks. We then analyze the roles of institutions in China to understand the relationships between power, human security and the socio-ecological system. To inform the study of conflicts over dams China is a particularly useful case study because we can examine what happens at the international, national and local scales. The powershed perspective allows us to examine resilience and vulnerability across political boundaries from a dynamic, process-defined analytical scale while remaining focused on a host of questions relating to hydro-development that invoke drivers and impacts on national and sub-national scales. The ability to disaggregate the affects of hydropower dam construction from political boundaries allows for a deeper analysis of resilience and vulnerability. From our analysis we find that reforms in China's hydropower sector since 1996 have been motivated by the need to create stability at the national scale rather than resilient solutions to China's growing demand for energy and water resource control at the local and international scales. Some measures that improved economic development through the market economy and a combination of dam construction and institutional reform may indeed improve hydro-political resilience at a single scale. However, if China does address large-scale hydropower construction's potential to create multi-scale geopolitical tensions, they may be vulnerable to conflict - though not necessarily violent - in domestic and international political arenas. We conclude with a look toward a resilient basin institution for the Nu/Salween River, the site of a proposed large-scale hydropower development effort in China and Myanmar.

  8. Effect of Environment and Sugar Beet Genotype on Root Rot Development and Pathogen Profile During Storage.

    PubMed

    Liebe, Sebastian; Varrelmann, Mark

    2016-01-01

    Storage rots represent an economically important factor impairing the storability of sugar beet by increasing sucrose losses and invert sugar content. Understanding the development of disease management strategies, knowledge about major storage pathogens, and factors influencing their occurrence is crucial. In comprehensive storage trials conducted under controlled conditions, the effects of environment and genotype on rot development and associated quality changes were investigated. Prevalent species involved in rot development were identified by a newly developed microarray. The strongest effect on rot development was assigned to environment factors followed by genotypic effects. Despite large variation in rot severity (sample range 0 to 84%), the spectrum of microorganisms colonizing sugar beet remained fairly constant across all treatments with dominant species belonging to the fungal genera Botrytis, Fusarium, and Penicillium. The intensity of microbial tissue necrotization was strongly correlated with sucrose losses (R² = 0.79 to 0.91) and invert sugar accumulation (R² = 0.91 to 0.95). A storage rot resistance bioassay was developed that could successfully reproduce the genotype ranking observed in storage trials. Quantification of fungal biomass indicates that genetic resistance is based on a quantitative mechanism. Further work is required to understand the large environmental influence on rot development in sugar beet.

  9. “Of Sheep and Men”: Earliest Direct Evidence of Caprine Domestication in Southern Africa at Leopard Cave (Erongo, Namibia)

    PubMed Central

    Pleurdeau, David; Imalwa, Emma; Détroit, Florent; Lesur, Joséphine; Veldman, Anzel; Bahain, Jean-Jacques; Marais, Eugène

    2012-01-01

    The origins of herding practices in southern Africa remain controversial. The first appearance of domesticated caprines in the subcontinent is thought to be c. 2000 years BP; however, the origin of this cultural development is still widely debated. Recent genetic analyses support the long-standing hypothesis of herder migration from the north, while other researchers have argued for a cultural diffusion hypothesis where the spread of herding practices took place without necessarily implicating simultaneous and large population movements. Here we document the Later Stone Age (LSA) site of Leopard Cave (Erongo, Namibia), which contains confirmed caprine remains, from which we infer that domesticates were present in the southern African region as early as the end of the first millennium BC. These remains predate the first evidence of domesticates previously recorded for the subcontinent. This discovery sheds new light on the emergence of herding practices in southern Africa, and also on the possible southward routes used by caprines along the western Atlantic coast. PMID:22808138

  10. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

    PubMed

    Adams, Hieab H H; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura M E; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; Braber, Anouk Den; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David C M; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Loohuis, Loes M Olde; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein M J; Van Eijk, Kristel R; Van Erp, Theo G M; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco J C; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald H H; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, W T; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W J H; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Hernández, Maria C Valdés; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic J A; Van Duijn, Cornelia M; Van Haren, Neeltje E M; Van T Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton J M; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-12-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  11. "Of sheep and men": earliest direct evidence of caprine domestication in southern Africa at Leopard Cave (Erongo, Namibia).

    PubMed

    Pleurdeau, David; Imalwa, Emma; Détroit, Florent; Lesur, Joséphine; Veldman, Anzel; Bahain, Jean-Jacques; Marais, Eugène

    2012-01-01

    The origins of herding practices in southern Africa remain controversial. The first appearance of domesticated caprines in the subcontinent is thought to be c. 2000 years BP; however, the origin of this cultural development is still widely debated. Recent genetic analyses support the long-standing hypothesis of herder migration from the north, while other researchers have argued for a cultural diffusion hypothesis where the spread of herding practices took place without necessarily implicating simultaneous and large population movements. Here we document the Later Stone Age (LSA) site of Leopard Cave (Erongo, Namibia), which contains confirmed caprine remains, from which we infer that domesticates were present in the southern African region as early as the end of the first millennium BC. These remains predate the first evidence of domesticates previously recorded for the subcontinent. This discovery sheds new light on the emergence of herding practices in southern Africa, and also on the possible southward routes used by caprines along the western Atlantic coast.

  12. Novel genetic loci underlying human intracranial volume identified through genome-wide association

    PubMed Central

    Adams, Hieab HH; Hibar, Derrek P; Chouraki, Vincent; Stein, Jason L; Nyquist, Paul A; Rentería, Miguel E; Trompet, Stella; Arias-Vasquez, Alejandro; Seshadri, Sudha; Desrivières, Sylvane; Beecham, Ashley H; Jahanshad, Neda; Wittfeld, Katharina; Van der Lee, Sven J; Abramovic, Lucija; Alhusaini, Saud; Amin, Najaf; Andersson, Micael; Arfanakis, Konstantinos; Aribisala, Benjamin S; Armstrong, Nicola J; Athanasiu, Lavinia; Axelsson, Tomas; Beiser, Alexa; Bernard, Manon; Bis, Joshua C; Blanken, Laura ME; Blanton, Susan H; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brickman, Adam M; Carmichael, Owen; Chakravarty, M Mallar; Chauhan, Ganesh; Chen, Qiang; Ching, Christopher RK; Cuellar-Partida, Gabriel; Den Braber, Anouk; Doan, Nhat Trung; Ehrlich, Stefan; Filippi, Irina; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Gottesman, Rebecca F; Greven, Corina U; Grimm, Oliver; Griswold, Michael E; Guadalupe, Tulio; Hass, Johanna; Haukvik, Unn K; Hilal, Saima; Hofer, Edith; Hoehn, David; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kasperaviciute, Dalia; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Liao, Jiemin; Liewald, David CM; Lopez, Lorna M; Luciano, Michelle; Macare, Christine; Marquand, Andre; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mazoyer, Bernard; McKay, David R; McWhirter, Rebekah; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Muetzel, Ryan L; Maniega, Susana Muñoz; Nho, Kwangsik; Nugent, Allison C; Olde Loohuis, Loes M; Oosterlaan, Jaap; Papmeyer, Martina; Pappa, Irene; Pirpamer, Lukas; Pudas, Sara; Pütz, Benno; Rajan, Kumar B; Ramasamy, Adaikalavan; Richards, Jennifer S; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rommelse, Nanda; Rose, Emma J; Royle, Natalie A; Rundek, Tatjana; Sämann, Philipp G; Satizabal, Claudia L; Schmaal, Lianne; Schork, Andrew J; Shen, Li; Shin, Jean; Shumskaya, Elena; Smith, Albert V; Sprooten, Emma; Strike, Lachlan T; Teumer, Alexander; Thomson, Russell; Tordesillas-Gutierrez, Diana; Toro, Roberto; Trabzuni, Daniah; Vaidya, Dhananjay; Van der Grond, Jeroen; Van der Meer, Dennis; Van Donkelaar, Marjolein MJ; Van Eijk, Kristel R; Van Erp, Theo GM; Van Rooij, Daan; Walton, Esther; Westlye, Lars T; Whelan, Christopher D; Windham, Beverly G; Winkler, Anderson M; Woldehawariat, Girma; Wolf, Christiane; Wolfers, Thomas; Xu, Bing; Yanek, Lisa R; Yang, Jingyun; Zijdenbos, Alex; Zwiers, Marcel P; Agartz, Ingrid; Aggarwal, Neelum T; Almasy, Laura; Ames, David; Amouyel, Philippe; Andreassen, Ole A; Arepalli, Sampath; Assareh, Amelia A; Barral, Sandra; Bastin, Mark E; Becker, Diane M; Becker, James T; Bennett, David A; Blangero, John; van Bokhoven, Hans; Boomsma, Dorret I; Brodaty, Henry; Brouwer, Rachel M; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bulayeva, Kazima B; Cahn, Wiepke; Calhoun, Vince D; Cannon, Dara M; Cavalleri, Gianpiero L; Chen, Christopher; Cheng, Ching-Yu; Cichon, Sven; Cookson, Mark R; Corvin, Aiden; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Dale, Anders M; Davies, Gareth E; De Geus, Eco JC; De Jager, Philip L; de Zubicaray, Greig I; Delanty, Norman; Depondt, Chantal; DeStefano, Anita L; Dillman, Allissa; Djurovic, Srdjan; Donohoe, Gary; Drevets, Wayne C; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Espeseth, Thomas; Evans, Denis A; Fedko, Iryna O; Fernández, Guillén; Ferrucci, Luigi; Fisher, Simon E; Fleischman, Debra A; Ford, Ian; Foroud, Tatiana M; Fox, Peter T; Francks, Clyde; Fukunaga, Masaki; Gibbs, J Raphael; Glahn, David C; Gollub, Randy L; Göring, Harald HH; Grabe, Hans J; Green, Robert C; Gruber, Oliver; Gudnason, Vilmundur; Guelfi, Sebastian; Hansell, Narelle K; Hardy, John; Hartman, Catharina A; Hashimoto, Ryota; Hegenscheid, Katrin; Heinz, Andreas; Le Hellard, Stephanie; Hernandez, Dena G; Heslenfeld, Dirk J; Ho, Beng-Choon; Hoekstra, Pieter J; Hoffmann, Wolfgang; Hofman, Albert; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Ikeda, Masashi; Ikram, M Kamran; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Jönsson, Erik G; Jukema, J Wouter; Kahn, René S; Kanai, Ryota; Kloszewska, Iwona; Knopman, David S; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Lemaître, Hervé; Liu, Xinmin; Longo, Dan L; Longstreth, WT; Lopez, Oscar L; Lovestone, Simon; Martinez, Oliver; Martinot, Jean-Luc; Mattay, Venkata S; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McMahon, Francis J; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Mosley, Thomas H; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Nalls, Michael A; Nauck, Matthias; Nichols, Thomas E; Niessen, Wiro J; Nöthen, Markus M; Nyberg, Lars; Ohi, Kazutaka; Olvera, Rene L; Ophoff, Roel A; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Pike, G Bruce; Potkin, Steven G; Psaty, Bruce M; Reppermund, Simone; Rietschel, Marcella; Roffman, Joshua L; Romanczuk-Seiferth, Nina; Rotter, Jerome I; Ryten, Mina; Sacco, Ralph L; Sachdev, Perminder S; Saykin, Andrew J; Schmidt, Reinhold; Schofield, Peter R; Sigurdsson, Sigurdur; Simmons, Andy; Singleton, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soininen, Hilkka; Srikanth, Velandai; Steen, Vidar M; Stott, David J; Sussmann, Jessika E; Thalamuthu, Anbupalam; Tiemeier, Henning; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Tzourio, Christophe; Uitterlinden, Andre G; Valdés Hernández, Maria C; Van der Brug, Marcel; Van der Lugt, Aad; Van der Wee, Nic JA; Van Duijn, Cornelia M; Van Haren, Neeltje EM; Van 't Ent, Dennis; Van Tol, Marie-Jose; Vardarajan, Badri N; Veltman, Dick J; Vernooij, Meike W; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M; Wassink, Thomas H; Weale, Michael E; Weinberger, Daniel R; Weiner, Michael W; Wen, Wei; Westman, Eric; White, Tonya; Wong, Tien Y; Wright, Clinton B; Zielke, H Ronald; Zonderman, Alan B; Deary, Ian J; DeCarli, Charles; Schmidt, Helena; Martin, Nicholas G; De Craen, Anton JM; Wright, Margaret J; Launer, Lenore J; Schumann, Gunter; Fornage, Myriam; Franke, Barbara; Debette, Stéphanie; Medland, Sarah E; Ikram, M Arfan; Thompson, Paul M

    2016-01-01

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth. PMID:27694991

  13. Machine Identification of Martian Craters Using Digital Elevation Data

    NASA Astrophysics Data System (ADS)

    Bue, B.; Stepinski, T. F.

    2005-12-01

    Impact craters are among the most studied features on Martian surface. Their importance stems from the worth of information that a detailed analysis of their number and morphology can bring forth. Because building manually a comprehensive dataset of craters is a laborious process, there have been many previous attempts to develop an automatic, image-based crater identifier. The resulting identifiers suffer from low efficiency and remain in an experimental stage. We have developed a DEM-based, fully autonomous crater identifier that takes an arbitrarily large Martian site as an input and produces a catalog of craters as an output. Using the topography data we calculate a topographic profile curvature that is thresholded to produce a binary image, pixels having maximum negative curvature are labeled black, the remaining pixels are labeled white. The black pixels outline craters because crater rims are the most convex feature in the Martian landscape. The Hough Transform (HT) is used for an actual recognition of craters in the binary image. The image is first segmented (without cutting the craters) into a large number of smaller images using the ``flood" algorithm that identifies basins. This segmentation makes possible the application of highly inefficient HT to large sites. The identifier is applied to a 106 km2 site located around the Herschel crater. According to the Barlow catalog, this site contains 485 craters >5 km. Our identifier finds 1099 segments, 628 of them are classified as craters >5 km. Overall, there is an excellent agreement between the two catalogs, although the specific statistics are still pending due to the difficulties in recalculating the MDIM 1 coordinate system used in the Barlow catalog to the MDIM 2.1 coordinate system used by our identifier.

  14. Construction, implementation, and evaluation of an undergraduate biology laboratory teaching model

    NASA Astrophysics Data System (ADS)

    Tarrant, Todd M.

    This dissertation documents a time series study in which an undergraduate non-majors biology laboratory was revised, leading to the development of a new teaching model. The course model was developed at a large Midwestern university enrolling about 827 students in 32 sections per semester and using graduate teaching assistants as primary instructors. The majority of the students consisted of freshman and sophomores, with the remainder being juniors and seniors. This dissertation explains the rationale leading to the development and implementation of this educational model using graduate teaching assistants as the primary course instructors and embedded course assessment as evidence of its success. The major components of this model include six major items including: learning community, course design, GTA professional development, course delivery, assessment, and the filter. The major aspects of this model include clear links between instruction, GTA professional development, embedded assessment (student and GTA), course revision, student perceptions, and performance. The model includes the following components: Formal and informal discourse in the learning community, teaching assistant professional development, the use of multiple assessment tools, a filter to guide course evaluation, and redirection and delivery of course content based on embedded formal course assessment. Teaching assistants receive both initial and ongoing professional development throughout the semester in effective instructional pedagogy from an instructor of record. Results for three years of operation show a significant increase in student biology content knowledge and the use of scientific process/critical thinking skills with mean improvement in student performance of 25.5% and 18.9% respectively. Mean attendance for ISB 208L is 95% for the six semesters of this study showing students regularly attend the laboratory classes and remain in the course with a completion rate of 93%. Additionally, grade point averages have remained high (mean of 3.3 for ISB 208L) while question cognitive level used on course assignments and tests has increased each semester while assignment weight has remained constant. Students indicate through SIRS data that the course is relevant to their lives, emphasizes understanding of ideas, concepts, and encourages students to think about the relationship between science and society. This study is significant in that it provides a description of a field tested working model for all aspects of a course that has large student enrollment, uses graduate teaching assistants as primary instructors, embedded course assessment, ongoing professional development, and general applicability in being transferable to other courses.

  15. Enhanced, targeted sampling of high-dimensional free-energy landscapes using variationally enhanced sampling, with an application to chignolin

    PubMed Central

    Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

    2016-01-01

    The capabilities of molecular simulations have been greatly extended by a number of widely used enhanced sampling methods that facilitate escaping from metastable states and crossing large barriers. Despite these developments there are still many problems which remain out of reach for these methods which has led to a vigorous effort in this area. One of the most important problems that remains unsolved is sampling high-dimensional free-energy landscapes and systems that are not easily described by a small number of collective variables. In this work we demonstrate a new way to compute free-energy landscapes of high dimensionality based on the previously introduced variationally enhanced sampling, and we apply it to the miniprotein chignolin. PMID:26787868

  16. A global survey of changing patterns of food allergy burden in children

    PubMed Central

    2013-01-01

    While food allergies and eczema are among the most common chronic non-communicable diseases in children in many countries worldwide, quality data on the burden of these diseases is lacking, particularly in developing countries. This 2012 survey was performed to collect information on existing data on the global patterns and prevalence of food allergy by surveying all the national member societies of the World Allergy Organization, and some of their neighbouring countries. Data were collected from 89 countries, including published data, and changes in the health care burden of food allergy. More than half of the countries surveyed (52/89) did not have any data on food allergy prevalence. Only 10% (9/89) of countries had accurate food allergy prevalence data, based on oral food challenges (OFC). The remaining countries (23/89) had data largely based on parent-reporting of a food allergy diagnosis or symptoms, which is recognised to overestimate the prevalence of food allergy. Based on more accurate measures, the prevalence of clinical (OFC proven) food allergy in preschool children in developed countries is now as high as 10%. In large and rapidly emerging societies of Asia, such as China, where there are documented increases in food allergy, the prevalence of OFC-proven food allergy is now around 7% in pre-schoolers, comparable to the reported prevalence in European regions. While food allergy appears to be increasing in both developed and developing countries in the last 10–15 years, there is a lack of quality comparative data. This survey also highlights inequities in paediatric allergy services, availability of adrenaline auto-injectors and standardised National Anaphylaxis Action plans. In conclusion, there remains a need to gather more accurate data on the prevalence of food allergy in many developed and developing countries to better anticipate and address the rising community and health service burden of food allergy. PMID:24304599

  17. Diel ontogenetic shift in parasitic activity in a gnathiid isopod on Caribbean coral reefs

    NASA Astrophysics Data System (ADS)

    Sikkel, P. C.; Ziemba, R. E.; Sears, W. T.; Wheeler, J. C.

    2009-06-01

    Ontogenetic niche shifts are characteristic of organisms with complex life cycles such as many marine invertebrates. Research has focused primarily on changes in habitat or diet. However, ontogenetic changes can also occur in the temporal pattern of foraging. Gnathiid isopods feed on fish blood throughout their larval stages and are the primary food item for cleaning organisms on coral reefs. At sites in Australia and the Caribbean, gnathiid larvae exhibit size-related differences in diel activity. However, it is unclear whether this is due to interspecific or intraspecific variation in behavior. Fish were deployed in cages near sunset on shallow reefs off St. John, U.S. Virgin Islands and allowed to be infected with larval gnathiids. Larvae collected from fish retrieved near midnight developed into adults, with most developing into females. In contrast, approximately 80% of gnathiids collected after first light developed into second or third stage larvae, and nearly all of the remaining, large, individuals developed into males. Comparison of ITS2 gene regions from individuals collected in emergence traps from the same reefs during the day versus during the night revealed no differences in this highly variable region. Thus, gnathiid larvae at this locality shift their time of activity as they develop, and larvae developing into males remain active over a longer time period than those developing into females.

  18. Learning to teach mathematics with technology: A survey of professional development needs, experiences and impacts

    NASA Astrophysics Data System (ADS)

    Bennison, Anne; Goos, Merrilyn

    2010-04-01

    The potential for digital technologies to enhance students' mathematics learning is widely recognised, and use of computers and graphics calculators is now encouraged or required by secondary school mathematics curriculum documents throughout Australia. However, previous research indicates that effective integration of technology into classroom practice remains patchy, with factors such as teacher knowledge, confidence, experience and beliefs, access to resources, and participation in professional development influencing uptake and implementation. This paper reports on a large-scale survey of technology-related professional development experiences and needs of Queensland secondary mathematics teachers. Teachers who had participated in professional development were found to be more confident in using technology and more convinced of its benefits in supporting students' learning of mathematics. Experienced, specialist mathematics teachers in large metropolitan schools were more likely than others to have attended technology-related professional development, with lack of time and limited access to resources acting as hindrances to many. Teachers expressed a clear preference for professional development that helps them meaningfully integrate technology into lessons to improve student learning of specific mathematical topics. These findings have implications for the design and delivery of professional development that improves teachers' knowledge, understanding, and skills in a diverse range of contexts.

  19. Integrity of Bolted Angle Connections Subjected to Simulated Column Removal

    PubMed Central

    Weigand, Jonathan M.; Berman, Jeffrey W.

    2016-01-01

    Large-scale tests of steel gravity framing systems (SGFSs) have shown that the connections are critical to the system integrity, when a column suffers damage that compromises its ability to carry gravity loads. When supporting columns were removed, the SGFSs redistributed gravity loads through the development of an alternate load path in a sustained tensile configuration resulting from large vertical deflections. The ability of the system to sustain such an alternate load path depends on the capacity of the gravity connections to remain intact after undergoing large rotation and axial extension demands, for which they were not designed. This study experimentally evaluates the performance of steel bolted angle connections subjected to loading consistent with an interior column removal. The characteristic connection behaviors are described and the performance of multiple connection configurations are compared in terms of their peak resistances and deformation capacities. PMID:27110059

  20. A Hybrid Coarse-graining Approach for Lipid Bilayers at Large Length and Time Scales

    PubMed Central

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    A hybrid analytic-systematic (HAS) coarse-grained (CG) lipid model is developed and employed in a large-scale simulation of a liposome. The methodology is termed hybrid analyticsystematic as one component of the interaction between CG sites is variationally determined from the multiscale coarse-graining (MS-CG) methodology, while the remaining component utilizes an analytic potential. The systematic component models the in-plane center of mass interaction of the lipids as determined from an atomistic-level MD simulation of a bilayer. The analytic component is based on the well known Gay-Berne ellipsoid of revolution liquid crystal model, and is designed to model the highly anisotropic interactions at a highly coarse-grained level. The HAS CG approach is the first step in an “aggressive” CG methodology designed to model multi-component biological membranes at very large length and timescales. PMID:19281167

  1. Beyond Linear Sequence Comparisons: The use of genome-levelcharacters for phylogenetic reconstruction

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

    Boore, Jeffrey L.

    2004-11-27

    Although the phylogenetic relationships of many organisms have been convincingly resolved by the comparisons of nucleotide or amino acid sequences, others have remained equivocal despite great effort. Now that large-scale genome sequencing projects are sampling many lineages, it is becoming feasible to compare large data sets of genome-level features and to develop this as a tool for phylogenetic reconstruction that has advantages over conventional sequence comparisons. Although it is unlikely that these will address a large number of evolutionary branch points across the broad tree of life due to the infeasibility of such sampling, they have great potential for convincinglymore » resolving many critical, contested relationships for which no other data seems promising. However, it is important that we recognize potential pitfalls, establish reasonable standards for acceptance, and employ rigorous methodology to guard against a return to earlier days of scenario-driven evolutionary reconstructions.« less

  2. Management of fish populations in large rivers: a review of tools and approaches

    USGS Publications Warehouse

    Petts, Geoffrey E.; Imhoff, Jack G.; Manny, Bruce A.; Maher, John F. B.; Weisberg, Stephen B.

    1989-01-01

    In common with most branches of science, the management of riverine fish populations is characterised by reductionist and isolationist philosophies. Traditional fish management focuses on stocking and controls on fishing. This paper presents a concensus of scientists involved in the LARS workshop on the management of fish populations in large rivers. A move towards a more holistic philosophy is advocated, with fish management forming an integral part of sustainable river development. Based upon a questionnaire survey of LARS members, with wide-ranging expertise and experience from all parts of the world, lists of management tools currently in use are presented. Four categories of tools are described: flow, water-quality, habitat, and biological. The potential applications of tools for fish management in large rivers is discussed and research needs are identified. The lack of scientific evaluations of the different tools remains the major constraint to their wider application.

  3. Structural Connectivity of the Developing Human Amygdala

    PubMed Central

    Saygin, Zeynep M.; Osher, David E.; Koldewyn, Kami; Martin, Rebecca E.; Finn, Amy; Saxe, Rebecca; Gabrieli, John D.E.; Sheridan, Margaret

    2015-01-01

    A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age. PMID:25875758

  4. Investigating Viruses during the Transformation of Molecular Biology

    PubMed Central

    2017-01-01

    This Reflections article describes my early work on viral enzymes and the discovery of mRNA capping, how my training in medicine and biochemistry merged as I evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970s and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (VACV), a large DNA virus with about 200 genes. The reader may view this article as a work in progress, because I remain actively engaged in research at the National Institutes of Health (NIH) notwithstanding 50 memorable years there. PMID:28154190

  5. The cell biology of mammalian fertilization.

    PubMed

    Okabe, Masaru

    2013-11-01

    Fertilization is the process by which eggs and spermatozoa interact, achieve mutual recognition, and fuse to create a zygote, which then develops to form a new individual, thus allowing for the continuity of a species. Despite numerous studies on mammalian fertilization, the molecular mechanisms underpinning the fertilization event remain largely unknown. However, as I summarize here, recent work using both gene-manipulated animals and in vitro studies has begun to elucidate essential sperm and egg molecules and to establish predictive models of successful fertilization.

  6. Mitral valve prolapse and Marfan syndrome.

    PubMed

    Thacoor, Amitabh

    2017-07-01

    Marfan syndrome is a multisystemic genetic condition affecting connective tissue. It carries a reduced life expectancy, largely dependent on cardiovascular complications. More common cardiac manifestations such as aortic dissection and aortic valve incompetence have been widely documented in the literature. Mitral valve prolapse (MVP), however, has remained poorly documented. This article aims at exploring the existing literature on the pathophysiology and diagnosis of MVP in patients with Marfan syndrome, defining its current management and outlining the future developments surrounding it. © 2017 Wiley Periodicals, Inc.

  7. Characterizing genomic alterations in cancer by complementary functional associations | Office of Cancer Genomics

    Cancer.gov

    Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment.

  8. Ocular melanoma: an overview of the current status

    PubMed Central

    Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav

    2013-01-01

    Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405

  9. Health consequences of the 'Great Recession' on the employed: evidence from an industrial cohort in aluminum manufacturing.

    PubMed

    Modrek, Sepideh; Cullen, Mark R

    2013-09-01

    While the negative effects of unemployment have been well studied, the consequences of layoffs and downsizing for those who remain employed are less well understood. This study uses human resources and health claims data from a large multi-site fully insured aluminum company to explore the health consequences of downsizing on the remaining workforce. We exploit the variation in the timing and intensity of layoff to categorize 30 plants as high or low layoff plants. Next, we select a stably employed cohort of workers with history of health insurance going back to 2006 to 1) describe the selection process into layoff and 2) explore the association between the severity of plant level layoffs and the incidence of four chronic conditions in the remaining workforce. We examine four health outcomes: incident hypertension, diabetes, asthma/COPD and depression for a cohort of approximately 13,000 employees. Results suggest that there was an increased risk of developing hypertension for all workers and an increased risk of developing diabetes for salaried workers that remain at the plants with the highest level of layoffs. The hypertension results were robust to a several specification tests. In addition, the study design selected only healthy workers, therefore our estimates are likely to be a lower bound and suggest that adverse health consequences of the 2007-2009 recession may have affected a broader proportion of the population than previously expected. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Illness and the Internet: From Private to Public Experience.

    PubMed

    Conrad, Peter; Bandini, Julia; Vasquez, Alexandria

    2016-01-01

    Illness is a ubiquitous experience in all societies. Until the past two decades, illness remained largely a private experience. With the development of the Internet, especially what has been termed Web 2.0, with interactive websites, illness has become increasingly a public experience. Vehicles like bulletin boards, chat rooms, listservs, electronic support groups, and more recently social media facilitate thousands of online communities where individuals with illness share information, interaction, experience, and advocacy. With the advent of social media, communication has increased and brought new challenges for online interaction. It is likely that the transformation of illness from a largely private to an increasingly public experience is a revolutionary change that is here to stay, with numerous social consequences. © The Author(s) 2015.

  11. Future Prospects for the Total Artificial Heart.

    PubMed

    Sunagawa, Gengo; Horvath, David J; Karimov, Jamshid H; Moazami, Nader; Fukamachi, Kiyotaka

    2016-01-01

    A total artificial heart (TAH) is the sole remaining option for patients with biventricular failure who cannot be rescued by left ventricular assist devices (LVADs) alone. However, the pulsatile TAH in clinical use today has limitations: large pump size, unknown durability, required complex anticoagulation regimen, and association with significant postsurgical complications. That pump is noisy; its large pneumatic driving lines traverse the body, with bulky external components for its drivers. Continuous-flow pumps, which caused a paradigm shift in the LVAD field, have already contributed to the rapidly evolving development of TAHs. Novel continuous-flow TAHs are only in preclinical testing or developmental stages. We here review the current state of TAHs, with recommended requirements for the TAH of the future.

  12. Advances in the manufacture of MIP nanoparticles.

    PubMed

    Poma, Alessandro; Turner, Anthony P F; Piletsky, Sergey A

    2010-12-01

    Molecularly imprinted polymers (MIPs) are prepared by creating a three-dimensional polymeric matrix around a template molecule. After the matrix is removed, complementary cavities with respect to shape and functional groups remain. MIPs have been produced for applications in in vitro diagnostics, therapeutics and separations. However, this promising technology still lacks widespread application because of issues related to large-scale production and optimization of the synthesis. Recent developments in the area of MIP nanoparticles might offer solutions to several problems associated with performance and application. This review discusses various approaches used in the preparation of MIP nanoparticles, focusing in particular on the issues associated with large-scale manufacture and implications for the performance of synthesized nanomaterials. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Design and testing of a new radio-tag for instrumenting large whales. Final report

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

    Follmann, E.H.; Miller, G.O.

    1981-03-01

    In 1978, Project Whales was initiated to investigate the occurrence, ecology, and biology of bowhead and gray whales in areas of the Beaufort Sea under consideration for offshore oil and gas leasing. One aspect of the study was to develop radio tags to monitor the movement and behavior of whales. It was considered important to test the radio tag design in more favorable environments than arctic waters. The test called for tagging of gray whales in Mexico with the objective to determine (1) effectiveness of the attachment procedure for tagging large whales (2) length of time the radio tag willmore » remain attached to a whale, and (3) range of reception from tagged whales.« less

  14. The role of community nursing in providing integrated care for older people with alcohol misuse.

    PubMed

    Rao, Tony

    2014-02-01

    Alcohol misuse in older people is a growing problem for health and social care providers, but remains largely hidden from public view and therefore largely overlooked by commissioners. Many older people with alcohol misuse have a 'dual diagnosis' (alcohol misuse accompanying other mental disorders) rather than alcohol misuse alone, which requires specialist nursing expertise. Over the past 10 years, assessment of and interventions for the detection of alcohol misuse in older people have been developed within one London borough. This article details the background, strategy and outcomes of this service, which provides integrated care in a multi-disciplinary community mental health team covering an inner-city area with a high prevalence of alcohol misuse and dual diagnosis in older people.

  15. Impacts of policy and market incentives for solid waste recycling in Dhaka, Bangladesh

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

    Matter, Anne; Swisscontact: Swiss Foundation for Technical Cooperation, South Asian Regional Office, House No. 19, Road No. 11, Baridhara, Dhaka 1212; Ahsan, Mehedi

    Highlights: • Bangladesh’s industry and population are growing rapidly, producing more urban waste. • Recycling reduces the solid waste management burden of Municipalities. • A wide array of informal and formal actors is involved in collection and recycling. • Demand for recycled materials and renewable energy creates market incentives. • Policy incentives exist, but they only reach the formal industry. - Abstract: Solid waste mismanagement in Dhaka, Bangladesh, illustrates a well-known market failure which can be summarized as: waste is a resource in the wrong place. Inorganic materials such as plastic or paper can be used to feed the demandmore » for recycled materials in the industrial sector. Organic materials can be converted and used in the nutrient-starved agricultural sector which is currently heavily depending on chemical fertilizers. They are also a feedstock to generate renewable energy in the form of biogas for this energy-starved country relying on diminishing natural gas reserves and increasing import of coal. Reality however does not capitalize on this potential; instead the waste is a burden for municipal authorities who spend large portions of their budgets attempting to transport it out of the city for discharge into landfills. The major part of these materials still remains uncollected in the residential areas and is discarded indiscriminately in open spaces, polluting the residents’ living environment including water, soil and air resources, in the city and beyond. Bangladeshi authorities have, to some extent, recognized this market failure and have developed policies to encourage the development of waste recycling activities. It is also important to note that this market failure is only partial: a large, mostly informal recycling sector has developed in Bangladesh, focusing on inorganic recyclables of market value. The fact that this sector remains largely informal means that these actors perceive significant barriers to formalization. Comparatively, the organic waste recycling sector is less driven by market mechanisms. Competition from chemical fertilizers and fossil fuels is fierce and hinders the development of market opportunities for compost and renewable energy. Nevertheless commercial production of compost and biogas from organic municipal waste is formalized and benefiting from policy incentives.« less

  16. Large-scale road safety programmes in low- and middle-income countries: an opportunity to generate evidence.

    PubMed

    Hyder, Adnan A; Allen, Katharine A; Peters, David H; Chandran, Aruna; Bishai, David

    2013-01-01

    The growing burden of road traffic injuries, which kill over 1.2 million people yearly, falls mostly on low- and middle-income countries (LMICs). Despite this, evidence generation on the effectiveness of road safety interventions in LMIC settings remains scarce. This paper explores a scientific approach for evaluating road safety programmes in LMICs and introduces such a road safety multi-country initiative, the Road Safety in 10 Countries Project (RS-10). By building on existing evaluation frameworks, we develop a scientific approach for evaluating large-scale road safety programmes in LMIC settings. This also draws on '13 lessons' of large-scale programme evaluation: defining the evaluation scope; selecting study sites; maintaining objectivity; developing an impact model; utilising multiple data sources; using multiple analytic techniques; maximising external validity; ensuring an appropriate time frame; the importance of flexibility and a stepwise approach; continuous monitoring; providing feedback to implementers, policy-makers; promoting the uptake of evaluation results; and understanding evaluation costs. The use of relatively new approaches for evaluation of real-world programmes allows for the production of relevant knowledge. The RS-10 project affords an important opportunity to scientifically test these approaches for a real-world, large-scale road safety evaluation and generate new knowledge for the field of road safety.

  17. Sequential and combinatorial roles of maf family genes define proper lens development.

    PubMed

    Reza, Hasan Mahmud; Urano, Atsuyo; Shimada, Naoko; Yasuda, Kunio

    2007-01-16

    Maf proteins have been shown to play pivotal roles in lens development in vertebrates. The developing chick lens expresses at least three large Maf proteins. However, the transcriptional relationship among the three large maf genes and their various roles in transactivating the downstream genes largely remain to be elucidated. Chick embryos were electroporated with wild-type L-maf, c-maf, and mafB by in ovo electroporation, and their effects on gene expression were determined by in situ hybridization using specific probes or by immunostaining. Endogenous gene expression was determined using nonelectroporated samples. A regulation mechanism exists among the members of maf family gene. An early-expressed member of this gene family typically stimulates the expression of later-expressed members. We also examined the regulation of various lens-expressing genes with a focus on the interaction between different Maf proteins. We found that the transcriptional ability of Maf proteins varies, even when the target is the same, in parallel with their discrete functions. L-Maf and c-Maf have no effect on E-cadherin expression, whereas MafB enhances its expression and thereby impedes lens vesicle formation. This study also revealed that Maf proteins can regulate the expression of gap junction genes, connexins, and their interacting partner, major intrinsic protein (MIP), during lens development. Misexpression of L-Maf and c-Maf induces ectopic expression of Cx43 and MIP; in contrast, MafB appears to have no effect on Cx43, but induces MIP significantly as evidenced from our gain-of-function experiments. Our results indicate that large Maf function is indispensable for chick lens initiation and development. In addition, L-Maf positively regulates most of the essential genes in this program and directs a series of molecular events leading to proper formation of the lens.

  18. Effect of large wood retention at check dams on sediment continuity

    NASA Astrophysics Data System (ADS)

    Schmocker, Lukas; Schalko, Isabella; Weitbrecht, Volker

    2017-04-01

    Large wood transport during flood events may seriously increase the damage potential due to accumulations at river infrastructures. The large wood is therefore mostly retained upstream of populated areas using retention structures that often combine a check dam with a debris rack. One disadvantages of this structures is, that the bed-load gets retained along with the wood. Especially if large wood blocks the rack early during a flood event, sediment continuity is completely interrupted. This may lead to severe bed erosion downstream of the check dam. So far, no common design to retain large wood but maintain sediment continuity is available. One attempt to separate the large wood from the bed-load was made with the large wood retention structure at River Sihl in Zürich, Switzerland. The retention of the large wood occurs in a bypass channel located along the main river. The bypass is located at an outer river bend, where a separation of bed-load and large wood results due to the secondary currents induced by the river curvature. Large wood floats towards the outer bend due to inertia and the secondary currents whereas bed-load remains at the inner bend. The bypass is separated by a side weir from the main river to ensure that the bed-load remains in the river during bed forming discharges and flood events. New model test are currently carried out at the Laboratory of Hydraulics, Hydrology, and Glaciology (VAW) of ETH Zurich, where sediment continuity should be achieved using an inclined rack. The rack is inclined in flow direction with a degree of 45° to 20°. First results show that the large wood deposits at the upper part of the rack whereas the lower part of the rack remains free for bed-load transport. Furthermore, the backwater rise for the inclined rack due to the accumulated wood is considerably reduced compared to a vertical rack, as a large part of the rack remains clear for the flow to pass. The findings of this studies help to understand the complex interaction between sediment and large wood at a check dam retention structure. Furthermore, new retention structures and rack designs are available, where sediment continuity can partially be maintained to reduce downstream bed erosion.

  19. Behavior of NiTiNb SMA wires under recovery stress or prestressing.

    PubMed

    Choi, Eunsoo; Nam, Tae-Hyun; Chung, Young-Soo; Kim, Yeon-Wook; Lee, Seung-Yong

    2012-01-05

    The recovery stress of martensitic shape-memory alloy [SMA] wires can be used to confine concrete, and the confining effectiveness of the SMA wires was previously proved through experimental tests. However, the behavior of SMA wires under recovery stress has not been seriously investigated. Thus, this study conducted a series of tests of NiTiNb martensitic SMA wires under recovery stress with varying degrees of prestrain on the wires and compared the behavior under recovery stress with that under prestressing of the wires. The remaining stress was reduced by the procedure of additional strain loading and unloading. More additional strains reduced more remaining stresses. When the SMA wires were heated up to the transformation temperature under prestress, the stress on the wires increased due to the state transformation. Furthermore, the stress decreased with a decreasing temperature of the wires down to room temperature. The stress of the NiTiNb wires was higher than the prestress, and the developed stress seemed to depend on the composition of the SMAs. When an additional strain was subsequently loaded and unloaded on the prestressed SMA wires, the remaining stress decreased. Finally, the remaining stress becomes zero when loading and unloading a specific large strain.

  20. The sand bag model of the dispersion of the cosmic body in the atmosphere

    NASA Technical Reports Server (NTRS)

    Teterev, A. V.; Nemchinov, I. V.

    1993-01-01

    The strength of the extraterrestrial bodies depends on their structure, composition, dimensions, and the history of this body. The fragmentation of the body due to aerodynamic stresses begins at sufficiently large heights above the surface of the Earth. The process of fragmentation and dispersion of the fragments usually is studied by the hydrodynamic or even gasdynamic models. If the fragmentation process begins due to the initial cracks and faults of the body, or this body consists of large boulders glued by ice, the strength of these boulders after fragmentation remains higher than the aerodynamic stresses exerted at the remaining part of the body. It is supposed that fragmentation occurs at initial moment t = 0 at some height z(sub o) above the surface of the air, these fragments remain solid. The possibility of further fragmentation during the remaining part of the trajectory is not taken into account. If the number of these parts is large enough and their size is small in comparison to the initial radius of the body than we can use the sand bag model proposed in qualitative form.

  1. Bioimage informatics for experimental biology

    PubMed Central

    Swedlow, Jason R.; Goldberg, Ilya G.; Eliceiri, Kevin W.

    2012-01-01

    Over the last twenty years there have been great advances in light microscopy with the result that multi-dimensional imaging has driven a revolution in modern biology. The development of new approaches of data acquisition are reportedly frequently, and yet the significant data management and analysis challenges presented by these new complex datasets remains largely unsolved. Like the well-developed field of genome bioinformatics, central repositories are and will be key resources, but there is a critical need for informatics tools in individual laboratories to help manage, share, visualize, and analyze image data. In this article we present the recent efforts by the bioimage informatics community to tackle these challenges and discuss our own vision for future development of bioimage informatics solution. PMID:19416072

  2. Gibberellic Acid: A Key Phytohormone for Spikelet Fertility in Rice Grain Production.

    PubMed

    Kwon, Choon-Tak; Paek, Nam-Chon

    2016-05-23

    The phytohormone gibberellic acid (GA) has essential signaling functions in multiple processes during plant development. In the "Green Revolution", breeders developed high-yield rice cultivars that exhibited both semi-dwarfism and altered GA responses, thus improving grain production. Most studies of GA have concentrated on germination and cell elongation, but GA also has a pivotal role in floral organ development, particularly in stamen/anther formation. In rice, GA signaling plays an important role in spikelet fertility; however, the molecular genetic and biochemical mechanisms of GA in male fertility remain largely unknown. Here, we review recent progress in understanding the network of GA signaling and its connection with spikelet fertility, which is tightly associated with grain productivity in cereal crops.

  3. Case for real-time systems development - Quo vadis?

    NASA Technical Reports Server (NTRS)

    Erb, Dona M.

    1991-01-01

    The paper focuses on the distinctive issues of computer-aided software engineering (CASE) products for the development of real-time systems. CASE technologies and associated standardization efforts are evolving from sets of conflicting interests. The majority of case products are intended for use in the development of management information systems. CASE products to support the development of large, complex real-time systems must provide additional capabilities. Generic concerns include the quality of the implementation of the required method for the phase of the system's development and whether the vendor is stable and committed to evolving the products in parallel with nonproprietary standards. The CASE market is undergoing considerable consolidation. The paper describes the major forces, cooperating entities, and remaining uncertainties that need to be weighed in near-term CASE procurements to limit risk of loss of investment in project time, trianing, and money.

  4. [Rabies vaccines: Current status and prospects for development].

    PubMed

    Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

    2015-01-01

    Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed.

  5. Vertebral Adaptations to Large Body Size in Theropod Dinosaurs.

    PubMed

    Wilson, John P; Woodruff, D Cary; Gardner, Jacob D; Flora, Holley M; Horner, John R; Organ, Chris L

    2016-01-01

    Rugose projections on the anterior and posterior aspects of vertebral neural spines appear throughout Amniota and result from the mineralization of the supraspinous and interspinous ligaments via metaplasia, the process of permanent tissue-type transformation. In mammals, this metaplasia is generally pathological or stress induced, but is a normal part of development in some clades of birds. Such structures, though phylogenetically sporadic, appear throughout the fossil record of non-avian theropod dinosaurs, yet their physiological and adaptive significance has remained unexamined. Here we show novel histologic and phylogenetic evidence that neural spine projections were a physiological response to biomechanical stress in large-bodied theropod species. Metaplastic projections also appear to vary between immature and mature individuals of the same species, with immature animals either lacking them or exhibiting smaller projections, supporting the hypothesis that these structures develop through ontogeny as a result of increasing bending stress subjected to the spinal column. Metaplastic mineralization of spinal ligaments would likely affect the flexibility of the spinal column, increasing passive support for body weight. A stiff spinal column would also provide biomechanical support for the primary hip flexors and, therefore, may have played a role in locomotor efficiency and mobility in large-bodied species. This new association of interspinal ligament metaplasia in Theropoda with large body size contributes additional insight to our understanding of the diverse biomechanical coping mechanisms developed throughout Dinosauria, and stresses the significance of phylogenetic methods when testing for biological trends, evolutionary or not.

  6. GPCR ontology: development and application of a G protein-coupled receptor pharmacology knowledge framework.

    PubMed

    Przydzial, Magdalena J; Bhhatarai, Barun; Koleti, Amar; Vempati, Uma; Schürer, Stephan C

    2013-12-15

    Novel tools need to be developed to help scientists analyze large amounts of available screening data with the goal to identify entry points for the development of novel chemical probes and drugs. As the largest class of drug targets, G protein-coupled receptors (GPCRs) remain of particular interest and are pursued by numerous academic and industrial research projects. We report the first GPCR ontology to facilitate integration and aggregation of GPCR-targeting drugs and demonstrate its application to classify and analyze a large subset of the PubChem database. The GPCR ontology, based on previously reported BioAssay Ontology, depicts available pharmacological, biochemical and physiological profiles of GPCRs and their ligands. The novelty of the GPCR ontology lies in the use of diverse experimental datasets linked by a model to formally define these concepts. Using a reasoning system, GPCR ontology offers potential for knowledge-based classification of individuals (such as small molecules) as a function of the data. The GPCR ontology is available at http://www.bioassayontology.org/bao_gpcr and the National Center for Biomedical Ontologies Web site.

  7. Blended particle filters for large-dimensional chaotic dynamical systems

    PubMed Central

    Majda, Andrew J.; Qi, Di; Sapsis, Themistoklis P.

    2014-01-01

    A major challenge in contemporary data science is the development of statistically accurate particle filters to capture non-Gaussian features in large-dimensional chaotic dynamical systems. Blended particle filters that capture non-Gaussian features in an adaptively evolving low-dimensional subspace through particles interacting with evolving Gaussian statistics on the remaining portion of phase space are introduced here. These blended particle filters are constructed in this paper through a mathematical formalism involving conditional Gaussian mixtures combined with statistically nonlinear forecast models compatible with this structure developed recently with high skill for uncertainty quantification. Stringent test cases for filtering involving the 40-dimensional Lorenz 96 model with a 5-dimensional adaptive subspace for nonlinear blended filtering in various turbulent regimes with at least nine positive Lyapunov exponents are used here. These cases demonstrate the high skill of the blended particle filter algorithms in capturing both highly non-Gaussian dynamical features as well as crucial nonlinear statistics for accurate filtering in extreme filtering regimes with sparse infrequent high-quality observations. The formalism developed here is also useful for multiscale filtering of turbulent systems and a simple application is sketched below. PMID:24825886

  8. Development of a high-content screening assay panel to accelerate mechanism of action studies for oncology research.

    PubMed

    Towne, Danli L; Nicholl, Emily E; Comess, Kenneth M; Galasinski, Scott C; Hajduk, Philip J; Abraham, Vivek C

    2012-09-01

    Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth-inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas.

  9. Examining practical nursing experiences to discover ways in which to retain and invigorate the remaining functions of the elderly with a demented and complex disability in nursing homes.

    PubMed

    Park, Min-Sun; Lim, Sun-Young; Kim, Eun-Young; Lee, Su-Jung; Chang, Sung-Ok

    2018-01-01

    The bedridden elderly with moderate-to-severe dementia account for a large proportion of the residents in nursing homes and form a specialized group requiring customized care in order to encourage their remaining functions, which determine the quality of their residual life. The purpose of this study was to search for ways to invigorate and foster the remaining functions of this complex-disability group, based on practical nursing strategies in nursing homes. The qualitative thematic analysis was done by conducting in-depth interviews with 29 nurses working at 11 different nursing homes in South Korea. This study proposed four main themes and 19 sub themes as keys for providing specialized nursing care to the elderly with physical and cognitive disabilities. The main themes encourage the residents' remaining functions: (i) accurate identification of an elderly resident's physical, cognitive, and behavioral baseline is necessary in order to determine their functional levels; (ii) nurses provide meticulous management to support the remaining functions in order to prevent further deterioration; (iii) optimized know-how, based on accumulated experience and knowledge, is reflected in nursing strategies that maximize the effects of nursing interventions; and (iv) steady compliance with nursing guidelines and standards in nursing homes creates the best therapeutic environment and brings unexpected positive changes in the elderly's status. A practical nursing strategy to target the group with a demented and complex disability in nursing homes was developed through thematic analysis of the empirical knowledge of nurses. The findings provide new insights for developing specialized nursing interventions and practical nursing models in long-term care facilities. © 2017 Japan Academy of Nursing Science.

  10. Characterization of Nanoreinforcement Dispersion in Inorganic Nanocomposites: A Review

    PubMed Central

    Saheb, Nouari; Qadir, Najam Ul; Siddiqui, Muhammad Usama; Arif, Abul Fazl Muhammad; Akhtar, Syed Sohail; Al-Aqeeli, Nasser

    2014-01-01

    Metal and ceramic matrix composites have been developed to enhance the stiffness and strength of metals and alloys, and improve the toughness of monolithic ceramics, respectively. It is possible to further improve their properties by using nanoreinforcement, which led to the development of metal and ceramic matrix nanocomposites, in which case, the dimension of the reinforcement is on the order of nanometer, typically less than 100 nm. However, in many cases, the properties measured experimentally remain far from those estimated theoretically. This is mainly due to the fact that the properties of nanocomposites depend not only on the properties of the individual constituents, i.e., the matrix and reinforcement as well as the interface between them, but also on the extent of nanoreinforcement dispersion. Therefore, obtaining a uniform dispersion of the nanoreinforcement in the matrix remains a key issue in the development of nanocomposites with the desired properties. The issue of nanoreinforcement dispersion was not fully addressed in review papers dedicated to processing, characterization, and properties of inorganic nanocomposites. In addition, characterization of nanoparticles dispersion, reported in literature, remains largely qualitative. The objective of this review is to provide a comprehensive description of characterization techniques used to evaluate the extent of nanoreinforcement dispersion in inorganic nanocomposites and critically review published work. Moreover, methodologies and techniques used to characterize reinforcement dispersion in conventional composites, which may be used for quantitative characterization of nanoreinforcement dispersion in nanocomposites, is also presented. PMID:28788670

  11. Cost effective technologies and renewable substrates for biosurfactants’ production

    PubMed Central

    Banat, Ibrahim M.; Satpute, Surekha K.; Cameotra, Swaranjit S.; Patil, Rajendra; Nyayanit, Narendra V.

    2014-01-01

    Diverse types of microbial surface active amphiphilic molecules are produced by a range of microbial communities. The extraordinary properties of biosurfactant/bioemulsifier (BS/BE) as surface active products allows them to have key roles in various field of applications such as bioremediation, biodegradation, enhanced oil recovery, pharmaceutics, food processing among many others. This leads to a vast number of potential applications of these BS/BE in different industrial sectors. Despite the huge number of reports and patents describing BS and BE applications and advantages, commercialization of these compounds remain difficult, costly and to a large extent irregular. This is mainly due to the usage of chemically synthesized media for growing producing microorganism and in turn the production of preferred quality products. It is important to note that although a number of developments have taken place in the field of BS industries, large scale production remains economically challenging for many types of these products. This is mainly due to the huge monetary difference between the investment and achievable productivity from the commercial point of view. This review discusses low cost, renewable raw substrates, and fermentation technology in BS/BE production processes and their role in reducing the production cost. PMID:25566213

  12. Modelling sea ice dynamics

    NASA Astrophysics Data System (ADS)

    Murawski, Jens; Kleine, Eckhard

    2017-04-01

    Sea ice remains one of the frontiers of ocean modelling and is of vital importance for the correct forecasts of the northern oceans. At large scale, it is commonly considered a continuous medium whose dynamics is modelled in terms of continuum mechanics. Its specifics are a matter of constitutive behaviour which may be characterised as rigid-plastic. The new developed sea ice dynamic module bases on general principles and follows a systematic approach to the problem. Both drift field and stress field are modelled by a variational property. Rigidity is treated by Lagrangian relaxation. Thus one is led to a sensible numerical method. Modelling fast ice remains to be a challenge. It is understood that ridging and the formation of grounded ice keels plays a role in the process. The ice dynamic model includes a parameterisation of the stress associated with grounded ice keels. Shear against the grounded bottom contact might lead to plastic deformation and the loss of integrity. The numerical scheme involves a potentially large system of linear equations which is solved by pre-conditioned iteration. The entire algorithm consists of several components which result from decomposing the problem. The algorithm has been implemented and tested in practice.

  13. Novel deletions involving the USH2A gene in patients with Usher syndrome and retinitis pigmentosa.

    PubMed

    García-García, Gema; Aller, Elena; Jaijo, Teresa; Aparisi, Maria J; Larrieu, Lise; Faugère, Valérie; Blanco-Kelly, Fiona; Ayuso, Carmen; Roux, Anne-Francoise; Millán, José M

    2014-01-01

    The aim of the present work was to identify and characterize large rearrangements involving the USH2A gene in patients with Usher syndrome and nonsyndromic retinitis pigmentosa. The multiplex ligation-dependent probe amplification (MLPA) technique combined with a customized array-based comparative genomic hybridization (aCGH) analysis was applied to 40 unrelated patients previously screened for point mutations in the USH2A gene in which none or only one pathologic mutation was identified. We detected six large deletions involving USH2A in six out of the 40 cases studied. Three of the patients were homozygous for the deletion, and the remaining three were compound heterozygous with a previously identified USH2A point mutation. In five of these cases, the patients displayed Usher type 2, and the remaining case displayed nonsyndromic retinitis pigmentosa. The exact breakpoint junctions of the deletions found in USH2A in four of these cases were characterized. Our study highlights the need to develop improved efficient strategies of mutation screening based upon next generation sequencing (NGS) that reduce cost, time, and complexity and allow simultaneous identification of all types of disease-causing mutations in diagnostic procedures.

  14. Management of facial burns with a collagen/glycosaminoglycan skin substitute-prospective experience with 12 consecutive patients with large, deep facial burns.

    PubMed

    Klein, Matthew B; Engrav, Loren H; Holmes, James H; Friedrich, Jeffrey B; Costa, Beth A; Honari, Shari; Gibran, Nicole S

    2005-05-01

    Management of deep facial burns remains one of the greatest challenges in burn care. We have developed a protocol over the past 20 years for management of facial burns that includes excision and coverage with thick autograft. However, the results were not perfect. Deformities of the eyelids, nose and mouth as well as the prominence of skin graft junctures demonstrated the need to explore novel approaches. Integra has been used with success in the management of burns of the trunk and extremities. The purpose of this study was to prospectively evaluate the aesthetic outcome of the use of Integra for deep facial burns. Twelve consecutive patients underwent excision of large, deep facial burns and placement of Integra. Integra provides excellent color and minimally visible skin graft junctures. The texture is good but not as supple as thick autograft. Integra is not well suited for use in the coverage of eyelid burns due to the need to wait 2 weeks for adequate vascularization. In summary, thick autograft remains the gold standard for deep facial burns. However, for patients with extensive burns and limited donor sites, Integra provides an acceptable alternative.

  15. Toxicological characteristics of edible insects in China: A historical review.

    PubMed

    Gao, Yu; Wang, Di; Xu, Meng-Lei; Shi, Shu-Sen; Xiong, Jin-Feng

    2018-04-10

    Edible insects are ideal food sources, which contain important nutrients and health-promoting compounds. With a rapid development of industrial insect farming, insect-derived food is a novel and emerging food industry. Edible insects have been traditionally consumed in various communities, while continuously gaining relevance in today's society; however, they currently remain underutilized. Although there are a large number of literature on edible insects, these literature primarily focus on the nutritional value edible insects. The toxicity assessment data of edible insects remain incomprehensive, especially for the new national standard that is currently in effect; and many data and conclusions are not accurately specified/reported. Therefore, we performed a literature review and summarized the data on the toxicological assessment of edible insects in China. The review first describes the research progress on safety toxicological assessment, and then offers references regarding the development of 34 edible insect species in China. These data can be a platform for the development of future toxicological assessment strategies, which can be carried out by a multidisciplinary team, possibly consisting of food engineers, agronomists, farmers, and so on, to improve the acceptability of edible insects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Enabling sustainable pastoralism: policies and investments that optimise livestock production and rangeland stewardship.

    PubMed

    Ouedraogo, R; Davies, J

    2016-11-01

    Pastoralism is a system of dynamically managing livestock and land for economic, social and environmental benefit. To a large extent, pastoralism is an adaptation to ecological and climatic variability and is not simply a livestock production system but provides significant environmental services to humanity. Evidence from a range of national contexts shows that sustainable pastoralist development requires an understanding of the dual environmental and economic roles of pastoralism and an adaptation of policies and investments to support both. The current paper examines three cornerstones that have proven to be crucial for sustainable pastoralist development and for maximising the links between livestock production and environmental stewardship: strengthening pastoral capabilities and institutions, securing land tenure and natural resource governance, and ensuring equitable markets for pastoral diversity. To effectively support the dual economic-environmental roles of pastoralism requires not only optimisation of the production of ecosystem services through extensive livestock production, but also a major overhaul of the way we approach pastoralist development, and major investment in the people who are central to the system. As long as pastoralists remain marginalised, with weak rights and little access to services, their future will remain uncertain.

  17. Developing Eastern Africa's resilience to flood and drought through multi-functional ecosystem-based management strategies

    NASA Astrophysics Data System (ADS)

    Lyon, Steve W.

    2017-04-01

    The rapid urbanization and agricultural expansion of Eastern Africa puts people in direct conflict with nature. Nowhere is this more obvious than for water resources where the delicate balance of too much water (flood) or too little water (drought) is a matter of life and death for millions. This work tackles this apparent conflict head-on by considering ecosystem service trade-offs relevant for water-based disasters as populations transition from rural to more intensive agricultural/urban lifestyles. Specifically, recent work from the Kilombero Valley of Tanzania, a region which has been targeted for development investment but where potential impacts (not to mention sustainability) associated with various development scenarios remain largely unresolved, will be presented as relevant case study. Our efforts on modelling and data synthesis for this region have shown promise as we seek to advance science in more and more remote (and in particular developing) regions while allowing important improvements for management of less and less available resources. Thus, in spite of large uncertainties the work highlights how research may still provide an improved system understanding of resource flows even when working under less than perfect conditions. Subsequently, such understanding feeds into development of frameworks for quantifying socio-hydrological impacts of land-water management. To ensure relevance regionally, we consider Kilombero Valley in the context of existing nature-based approaches dealing with disaster risk reduction. Such context potentially facilitates transfer of knowledge across country borders. Our goal here is to empower planners and stakeholders throughout the region by helping translate their knowledge into optimized adaptation strategies and linking their experiences through South-South transfer. There remains an open (and fundamental) question of how to best define management recommendations and activities that not only achieve climate resiliency but also are acceptable for stakeholders without compromising ecosystem service supplies.

  18. Radiation countermeasure agents: an update (2011 – 2014)

    PubMed Central

    Newman, Victoria L; Romaine, Patricia LP; Wise, Stephen Y; Seed, Thomas M

    2014-01-01

    Introduction Despite significant scientific advances over the past 60 years towards the development of a safe, nontoxic and effective radiation countermeasure for the acute radiation syndrome (ARS), no drug has been approved by the US FDA. A radiation countermeasure to protect the population at large from the effects of lethal radiation exposure remains a significant unmet medical need of the US citizenry and, thus, has been recognized as a high priority area by the government. Area covered This article reviews relevant publications and patents for recent developments and progress for potential ARS treatments in the area of radiation countermeasures. Emphasis is placed on the advanced development of existing agents since 2011 and new agents identified as radiation countermeasure for ARS during this period. Expert opinion A number of promising radiation countermeasures are currently under development, seven of which have received US FDA investigational new drug status for clinical investigation. Four of these agents, CBLB502, Ex-RAD, HemaMax and OrbeShield, are progressing with large animal studies and clinical trials. G-CSF has high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the US FDA in the future. PMID:25315070

  19. Effects of chromosomal sex and hormonal influences on shaping sex differences in brain and behavior: Lessons from cases of disorders of sex development.

    PubMed

    Bramble, Matthew S; Lipson, Allen; Vashist, Neerja; Vilain, Eric

    2017-01-02

    Sex differences in brain development and postnatal behavior are determined largely by genetic sex and in utero gonadal hormone secretions. In humans however, determining the weight that each of these factors contributes remains a challenge because social influences should also be considered. Cases of disorders of sex development (DSD) provide unique insight into how mutations in genes responsible for gonadal formation can perturb the subsequent developmental hormonal milieu and elicit changes in normal human brain maturation. Specific forms of DSDs such as complete androgen insensitivity syndrome (CAIS), congenital adrenal hyperplasia (CAH), and 5α-reductase deficiency syndrome have variable effects between males and females, and the developmental outcomes of such conditions are largely dependent on sex chromosome composition. Medical and psychological works focused on CAH, CAIS, and 5α-reductase deficiency have helped form the foundation for understanding the roles of genetic and hormonal factors necessary for guiding human brain development. Here we highlight how the three aforementioned DSDs contribute to brain and behavioral phenotypes that can uniquely affect 46,XY and 46,XX individuals in dramatically different fashions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. European Vaccine Initiative: lessons from developing malaria vaccines.

    PubMed

    Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

    2011-12-01

    For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

  1. Visual Circuit Development Requires Patterned Activity Mediated by Retinal Acetylcholine Receptors

    PubMed Central

    Burbridge, Timothy J.; Xu, Hong-Ping; Ackman, James B.; Ge, Xinxin; Zhang, Yueyi; Ye, Mei-Jun; Zhou, Z. Jimmy; Xu, Jian; Contractor, Anis; Crair, Michael C.

    2014-01-01

    SUMMARY The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial largely due to the inherent difficulty recording neural activity in early development. Here, we describe novel genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a de-coupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience. PMID:25466916

  2. Lessons learned: Infrastructure development and financial management for large, publically funded, international trials

    PubMed Central

    Larson, Gregg S; Carey, Cate; Grarup, Jesper; Hudson, Fleur; Sachi, Karen; Vjecha, Michael J; Gordin, Fred

    2015-01-01

    Background/Aims Randomized clinical trials are widely recognized as essential to address world-wide clinical and public health research questions. However, for many conditions, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost. We identify approaches and practices for large, publicly-funded, international trials that reduce cost without compromising data integrity, and recommend an approach to cost reporting that permits comparison of clinical trials. Methods We describe the organizational and financial characteristics of INSIGHT, an infectious disease research network that conducts multiple, large, long-term, international trials, and examine challenges associated with simple and streamlined governance and an infrastructure and financial management model that is based on performance, transparency, and accountability. Results It is possible to reduce costs of participant follow-up and not compromise clinical trial quality or integrity. The INSIGHT network has successfully completed four large HIV trials using cost-efficient practices that have not adversely affected investigator enthusiasm, accrual rates, loss-to-follow-up, adherence to the protocol, and completion of data collection. This experience is relevant to the conduct of large, publically funded trials in other disease areas, particularly trials dependent on international collaborations. Conclusion New approaches, or creative adaption of traditional clinical trial infrastructure and financial management tools, can render large, international clinical trials more cost-efficient by emphasizing structural simplicity; minimal up-front costs; payments for performance; and uniform algorithms and fees-for-service, irrespective of location. However, challenges remain. They include institutional resistance to financial change, growing trial complexity, and the difficulty of sustaining network infrastructure absent stable research work. There is also a need for more central monitoring, improved and harmonized regulations, and a widely-applied metric for measuring and comparing cost efficiency in clinical trials. ClinicalTrials.gov is recommended as a location where standardized trial cost information could be made publicly accessible. PMID:26908541

  3. Structural and functional studies of a family of Dictyostelium discoideum developmentally regulated, prestalk genes coding for small proteins.

    PubMed

    Vicente, Juan J; Galardi-Castilla, María; Escalante, Ricardo; Sastre, Leandro

    2008-01-03

    The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation. Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87-89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development. A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.

  4. CloudSat-Constrained Cloud Ice Water Path and Cloud Top Height Retrievals from MHS 157 and 183.3 GHz Radiances

    NASA Technical Reports Server (NTRS)

    Gong, J.; Wu, D. L.

    2014-01-01

    Ice water path (IWP) and cloud top height (ht) are two of the key variables in determining cloud radiative and thermodynamical properties in climate models. Large uncertainty remains among IWP measurements from satellite sensors, in large part due to the assumptions made for cloud microphysics in these retrievals. In this study, we develop a fast algorithm to retrieve IWP from the 157, 183.3+/-3 and 190.3 GHz radiances of the Microwave Humidity Sounder (MHS) such that the MHS cloud ice retrieval is consistent with CloudSat IWP measurements. This retrieval is obtained by constraining the empirical forward models between collocated and coincident measurements of CloudSat IWP and MHS cloud-induced radiance depression (Tcir) at these channels. The empirical forward model is represented by a lookup table (LUT) of Tcir-IWP relationships as a function of ht and the frequency channel.With ht simultaneously retrieved, the IWP is found to be more accurate. The useful range of the MHS IWP retrieval is between 0.5 and 10 kg/sq m, and agrees well with CloudSat in terms of the normalized probability density function (PDF). Compared to the empirical model, current operational radiative transfer models (RTMs) still have significant uncertainties in characterizing the observed Tcir-IWP relationships. Therefore, the empirical LUT method developed here remains an effective approach to retrieving ice cloud properties from the MHS-like microwave channels.

  5. Investigational drugs to treat methicillin-resistant Staphylococcus aureus

    PubMed Central

    Vuong, Cuong; Yeh, Anthony J; Cheung, Gordon YC; Otto, Michael

    2016-01-01

    Introduction Staphylococcus aureus remains one of the leading causes of morbidity and mortality worldwide. This is to a large extent due to antibiotic-resistant strains, in particular methicillin-resistant S. aureus (MRSA). While the toll of invasive MRSA infections appears to decrease in U.S. hospitals, the rate of community-associated MRSA infections remains constant and there is a surge of MRSA in many other countries. This situation calls for continuing if not increased efforts to find novel strategies to combat MRSA infections. Areas covered This review will provide an overview of current investigational antibiotics in clinical development (up to phase II), and of therapeutic antibodies and alternative drugs against S. aureus in preclinical and clinical development, including a short description of the mechanism of action and a presentation of microbiological and clinical data. Expert opinion Increased recent antibiotic development efforts and results from pathogenesis research have led to several new antibiotics and alternative drugs, as well as a more informed selection of targets for vaccination efforts against MRSA. This developing portfolio of novel anti-staphylococcal drugs will hopefully provide us with additional and more efficient ways to combat MRSA infections in the near future and prevent us from running out of treatment options, even if new resistances arise. PMID:26536498

  6. Eradication of tetanus

    PubMed Central

    Thwaites, C. L.; Loan, H. T.

    2015-01-01

    Introduction The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Sources of data Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. Areas of agreement The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Areas of controversy Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. Areas timely for developing research It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. PMID:26598719

  7. Cholera: current epidemiology.

    PubMed

    Crowcroft, N S

    1994-12-09

    Cholera remains an important cause of morbidity and mortality worldwide. Its epidemiology has changed in the 1990s, with the spread of the seventh pandemic to the western hemisphere and the emergence of a new serogroup, Vibrio cholerae O139. The spread of cholera may be rapid and unpredictable because of aeroplane travel, international shipping, and the migration of people due to war or political unrest. Increasing amounts of largely untreated faeces from growing human populations favour cholera's survival. Most of the world has inadequate sanitation, and future prospects are undermined by the impact of international debt on ailing economies. Furthermore, because cholera is difficult to eradicate from water it is likely to remain a serious threat to public health for some time. Progress is being made in the development of oral vaccines against V. cholerae O1 and serogroup O139.

  8. Effect of gas adsorption on acoustic wave propagation in MFI zeolite membrane materials: experiment and molecular simulation.

    PubMed

    Manga, Etoungh D; Blasco, Hugues; Da-Costa, Philippe; Drobek, Martin; Ayral, André; Le Clezio, Emmanuel; Despaux, Gilles; Coasne, Benoit; Julbe, Anne

    2014-09-02

    The present study reports on the development of a characterization method of porous membrane materials which consists of considering their acoustic properties upon gas adsorption. Using acoustic microscopy experiments and atomistic molecular simulations for helium adsorbed in a silicalite-1 zeolite membrane layer, we showed that acoustic wave propagation could be used, in principle, for controlling the membranes operando. Molecular simulations, which were found to fit experimental data, showed that the compressional modulus of the composite system consisting of silicalite-1 with adsorbed He increases linearly with the He adsorbed amount while its shear modulus remains constant in a large range of applied pressures. These results suggest that the longitudinal and Rayleigh wave velocities (VL and VR) depend on the He adsorbed amount whereas the transverse wave velocity VT remains constant.

  9. Advances in cancer stem cell targeting: How to strike the evil at its root.

    PubMed

    Pützer, Brigitte M; Solanki, Manish; Herchenröder, Ottmar

    2017-10-01

    Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads. Another emphasis lies on novel proceedings envisaged to deliver current and prospective therapies to the target sites using newest viral and non-viral vector technologies. In this review, we summarize recent progress and remaining challenges in therapeutic strategies to combat CSC. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Diet, ageing and genetic factors in the pathogenesis of diverticular disease

    PubMed Central

    Commane, Daniel Martin; Arasaradnam, Ramesh Pulendran; Mills, Sarah; Mathers, John Cummings; Bradburn, Mike

    2009-01-01

    Diverticular disease (DD) is an age-related disorder of the large bowel which may affect half of the population over the age of 65 in the UK. This high prevalence ranks it as one of the most common bowel disorders in western nations. The majority of patients remain asymptomatic but there are associated life-threatening co-morbidities, which, given the large numbers of people with DD, translates into a considerable number of deaths per annum. Despite this public health burden, relatively little seems to be known about either the mechanisms of development or causality. In the 1970s, a model of DD formulated the concept that diverticula occur as a consequence of pressure-induced damage to the colon wall amongst those with a low intake of dietary fiber. In this review, we have examined the evidence regarding the influence of ageing, diet, inflammation and genetics on DD development. We argue that the evidence supporting the barotrauma hypothesis is largely anecdotal. We have also identified several gaps in the knowledge base which need to be filled before we can complete a model for the etiology of diverticular disease. PMID:19468998

  11. Present status of the low energy linac-based slow positron beam and positronium spectrometer in Saclay

    NASA Astrophysics Data System (ADS)

    Liszkay, L.; Comini, P.; Corbel, C.; Debu, P.; Grandemange, P.; Pérez, P.; Rey, J.-M.; Reymond, J.-M.; Ruiz, N.; Sacquin, Y.; Vallage, B.

    2014-04-01

    A new slow positron beamline featuring a large acceptance positronium lifetime spectrometer has been constructed and tested at the linac-based slow positron source at IRFU CEA Saclay, France. The new instrument will be used in the development of a dense positronium target cloud for the GBAR experiment. The GBAR project aims at precise measurement of the gravitational acceleration of antihydrogen in the gravitational field of the Earth. Beyond application in fundamental science, the positron spectrometer will be used in materials research, for testing thin porous films and layers by means of positronium annihilation. The slow positron beamline is being used as a test bench to develop further instrumentation for positron annihilation spectroscopy (Ps time-of-flight, pulsed positron beam). The positron source is built on a low energy linear electron accelerator (linac). The 4.3 MeV electron energy used is well below the photoneutron threshold, making the source a genuine on-off device, without remaining radioactivity. The spectrometer features large BGO (Bismuth Germanate) scintillator detectors, with sufficiently large acceptance to detect all ortho-positronium annihilation lifetime components (annihilation in vacuum and in nanopores).

  12. The relationship between gastrointestinal motility and gastric dilatation-volvulus in dogs.

    PubMed

    Gazzola, Krista M; Nelson, Laura L

    2014-09-01

    Gastric dilatation-volvulus (GDV) is a devastating disease that most commonly affects large and giant-breed dogs. Though a number of risk factors have been associated with the development of GDV, the etiology of GDV remains unclear. Abnormal gastric motility patterns and delayed gastric emptying have been previously described in dogs following GDV. Work evaluating the effects of gastropexy procedures and changes to gastric motility after experimental GDV has not found the same changes as those found in dogs with naturally occurring GDV. Although the role of abnormal gastric motility in dogs with GDV will need to be clarified with additional research, such study is likely to be facilitated by improved access to and development of noninvasive measurement techniques for the evaluation of gastric emptying and other motility parameters. In particular, the availability of Food and Drug Administration-approved wireless motility devices for the evaluation of gastrointestinal motility is particularly promising in the study of GDV and other functional gastrointestinal diseases of large and giant-breed dogs. Published by Elsevier Inc.

  13. CRIMALDDI: a co-ordinated, rational, and integrated effort to set logical priorities in anti-malarial drug discovery initiatives

    PubMed Central

    2010-01-01

    Despite increasing efforts and support for anti-malarial drug R&D, globally anti-malarial drug discovery and development remains largely uncoordinated and fragmented. The current window of opportunity for large scale funding of R&D into malaria is likely to narrow in the coming decade due to a contraction in available resources caused by the current economic difficulties and new priorities (e.g. climate change). It is, therefore, essential that stakeholders are given well-articulated action plans and priorities to guide judgments on where resources can be best targeted. The CRIMALDDI Consortium (a European Union funded initiative) has been set up to develop, through a process of stakeholder and expert consultations, such priorities and recommendations to address them. It is hoped that the recommendations will help to guide the priorities of the European anti-malarial research as well as the wider global discovery agenda in the coming decade. PMID:20626844

  14. ACTIVIS: Visual Exploration of Industry-Scale Deep Neural Network Models.

    PubMed

    Kahng, Minsuk; Andrews, Pierre Y; Kalro, Aditya; Polo Chau, Duen Horng

    2017-08-30

    While deep learning models have achieved state-of-the-art accuracies for many prediction tasks, understanding these models remains a challenge. Despite the recent interest in developing visual tools to help users interpret deep learning models, the complexity and wide variety of models deployed in industry, and the large-scale datasets that they used, pose unique design challenges that are inadequately addressed by existing work. Through participatory design sessions with over 15 researchers and engineers at Facebook, we have developed, deployed, and iteratively improved ACTIVIS, an interactive visualization system for interpreting large-scale deep learning models and results. By tightly integrating multiple coordinated views, such as a computation graph overview of the model architecture, and a neuron activation view for pattern discovery and comparison, users can explore complex deep neural network models at both the instance- and subset-level. ACTIVIS has been deployed on Facebook's machine learning platform. We present case studies with Facebook researchers and engineers, and usage scenarios of how ACTIVIS may work with different models.

  15. Small Project Rapid Integration and Test Environment (SPRITE) An Innovation Space for Small Projects Design, Development, Integration, and Test

    NASA Technical Reports Server (NTRS)

    Lee, Ashley; Rackoczy, John; Heater, Daniel; Sanders, Devon; Tashakkor, Scott

    2013-01-01

    Over the past few years interest in the development and use of small satellites has rapidly gained momentum with universities, commercial, and government organizations. In a few years we may see networked clusters of dozens or even hundreds of small, cheap, easily replaceable satellites working together in place of the large, expensive and difficult-to-replace satellites now in orbit. Standards based satellite buses and deployment mechanisms, such as the CubeSat and Poly Pico-satellite Orbital Deployer (P-POD), have stimulated growth in this area. The use of small satellites is also proving to be a cost effective capability in many areas traditionally dominated by large satellites, though many challenges remain. Currently many of these small satellites undergo very little testing prior to flight. As these small satellites move from technology demonstration and student projects toward more complex operational assets, it is expected that the standards for verification and validation will increase.

  16. Assessing large-scale wildlife responses to human infrastructure development

    PubMed Central

    Torres, Aurora; Jaeger, Jochen A. G.; Alonso, Juan Carlos

    2016-01-01

    Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future. PMID:27402749

  17. Assessing large-scale wildlife responses to human infrastructure development.

    PubMed

    Torres, Aurora; Jaeger, Jochen A G; Alonso, Juan Carlos

    2016-07-26

    Habitat loss and deterioration represent the main threats to wildlife species, and are closely linked to the expansion of roads and human settlements. Unfortunately, large-scale effects of these structures remain generally overlooked. Here, we analyzed the European transportation infrastructure network and found that 50% of the continent is within 1.5 km of transportation infrastructure. We present a method for assessing the impacts from infrastructure on wildlife, based on functional response curves describing density reductions in birds and mammals (e.g., road-effect zones), and apply it to Spain as a case study. The imprint of infrastructure extends over most of the country (55.5% in the case of birds and 97.9% for mammals), with moderate declines predicted for birds (22.6% of individuals) and severe declines predicted for mammals (46.6%). Despite certain limitations, we suggest the approach proposed is widely applicable to the evaluation of effects of planned infrastructure developments under multiple scenarios, and propose an internationally coordinated strategy to update and improve it in the future.

  18. Region Evolution eXplorer - A tool for discovering evolution trends in ontology regions.

    PubMed

    Christen, Victor; Hartung, Michael; Groß, Anika

    2015-01-01

    A large number of life science ontologies has been developed to support different application scenarios such as gene annotation or functional analysis. The continuous accumulation of new insights and knowledge affects specific portions in ontologies and thus leads to their adaptation. Therefore, it is valuable to study which ontology parts have been extensively modified or remained unchanged. Users can monitor the evolution of an ontology to improve its further development or apply the knowledge in their applications. Here we present REX (Region Evolution eXplorer) a web-based system for exploring the evolution of ontology parts (regions). REX provides an analysis platform for currently about 1,000 versions of 16 well-known life science ontologies. Interactive workflows allow an explorative analysis of changing ontology regions and can be used to study evolution trends for long-term periods. REX is a web application providing an interactive and user-friendly interface to identify (un)stable regions in large life science ontologies. It is available at http://www.izbi.de/rex.

  19. Aerobic exercise and other healthy lifestyle factors that influence vascular aging.

    PubMed

    Santos-Parker, Jessica R; LaRocca, Thomas J; Seals, Douglas R

    2014-12-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote "resistance" against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. Copyright © 2014 The American Physiological Society.

  20. Aerobic exercise and other healthy lifestyle factors that influence vascular aging

    PubMed Central

    Santos-Parker, Jessica R.; LaRocca, Thomas J.

    2014-01-01

    Cardiovascular diseases (CVDs) remain the leading cause of death in the United States and other modern societies. Advancing age is the major risk factor for CVD, primarily due to stiffening of the large elastic arteries and the development of vascular endothelial dysfunction. In contrast, regular aerobic exercise protects against the development of large elastic artery stiffness and vascular endothelial dysfunction with advancing age. Moreover, aerobic exercise interventions reduce arterial stiffness and restore vascular endothelial function in previously sedentary middle-aged/older adults. Aerobic exercise exerts its beneficial effects on arterial function by modulating structural proteins, reducing oxidative stress and inflammation, and restoring nitric oxide bioavailability. Aerobic exercise may also promote “resistance” against factors that reduce vascular function and increase CVD risk with age. Preventing excessive increases in abdominal adiposity, following healthy dietary practices, maintaining a low CVD risk factor profile, and, possibly, selective use of pharmaceuticals and nutraceuticals also play a major role in preserving vascular function with aging. PMID:25434012

  1. Current Approaches to Bone Tissue Engineering: The Interface between Biology and Engineering.

    PubMed

    Li, Jiao Jiao; Ebied, Mohamed; Xu, Jen; Zreiqat, Hala

    2018-03-01

    The successful regeneration of bone tissue to replace areas of bone loss in large defects or at load-bearing sites remains a significant clinical challenge. Over the past few decades, major progress is achieved in the field of bone tissue engineering to provide alternative therapies, particularly through approaches that are at the interface of biology and engineering. To satisfy the diverse regenerative requirements of bone tissue, the field moves toward highly integrated approaches incorporating the knowledge and techniques from multiple disciplines, and typically involves the use of biomaterials as an essential element for supporting or inducing bone regeneration. This review summarizes the types of approaches currently used in bone tissue engineering, beginning with those primarily based on biology or engineering, and moving into integrated approaches in the areas of biomaterial developments, biomimetic design, and scalable methods for treating large or load-bearing bone defects, while highlighting potential areas for collaboration and providing an outlook on future developments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Impact of perinatal environmental tobacco smoke on the development of childhood allergic diseases.

    PubMed

    Yang, Hyeon-Jong

    2016-08-01

    Allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, and food allergy, are most common chronic, noncommunicable diseases in childhood. In the past few decades, the prevalence has increased abruptly worldwide. There are 2 possible explanations for the rising prevalence of allergic diseases worldwide, that an increased disease-awareness of physician, patient, or caregivers, and an abrupt exposure to unknown hazards. Unfortunately, the underlying mechanisms remain largely unknown. Despite the continuing efforts worldwide, the etiologies and rising prevalence remain unclear. Thus, it is important to identify and control risk factors in the susceptible individual for the best prevention and management. Genetic susceptibility or environments may be a potential background for the development of allergic disease, however they alone cannot explain the rising prevalence worldwide. There is growing evidence that epigenetic change depends on the gene, environment, and their interactions, may induce a long-lasting altered gene expression and the consequent development of allergic diseases. In epigenetic mechanisms, environmental tobacco smoke (ETS) exposure during critical period (i.e., during pregnancy and early life) are considered as a potential cause of the development of childhood allergic diseases. However, the causal relationship is still unclear. This review aimed to highlight the impact of ETS exposure during the perinatal period on the development of childhood allergic diseases and to propose a future research direction.

  3. Spatial organization of chromatin domains and compartments in single chromosomes

    NASA Astrophysics Data System (ADS)

    Wang, Siyuan; Su, Jun-Han; Beliveau, Brian; Bintu, Bogdan; Moffitt, Jeffrey; Wu, Chao-Ting; Zhuang, Xiaowei

    The spatial organization of chromatin critically affects genome function. Recent chromosome-conformation-capture studies have revealed topologically associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here, we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized manner in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.

  4. Video Browsing on Handheld Devices

    NASA Astrophysics Data System (ADS)

    Hürst, Wolfgang

    Recent improvements in processing power, storage space, and video codec development enable users now to playback video on their handheld devices in a reasonable quality. However, given the form factor restrictions of such a mobile device, screen size still remains a natural limit and - as the term "handheld" implies - always will be a critical resource. This is not only true for video but any data that is processed on such devices. For this reason, developers have come up with new and innovative ways to deal with large documents in such limited scenarios. For example, if you look at the iPhone, innovative techniques such as flicking have been introduced to skim large lists of text (e.g. hundreds of entries in your music collection). Automatically adapting the zoom level to, for example, the width of table cells when double tapping on the screen enables reasonable browsing of web pages that have originally been designed for large, desktop PC sized screens. A multi touch interface allows you to easily zoom in and out of large text documents and images using two fingers. In the next section, we will illustrate that advanced techniques to browse large video files have been developed in the past years, as well. However, if you look at state-of-the-art video players on mobile devices, normally just simple, VCR like controls are supported (at least at the time of this writing) that only allow users to just start, stop, and pause video playback. If supported at all, browsing and navigation functionality is often restricted to simple skipping of chapters via two single buttons for backward and forward navigation and a small and thus not very sensitive timeline slider.

  5. Developmental transcriptional profiling reveals key insights into Triticeae reproductive development.

    PubMed

    Tran, Frances; Penniket, Carolyn; Patel, Rohan V; Provart, Nicholas J; Laroche, André; Rowland, Owen; Robert, Laurian S

    2013-06-01

    Despite their importance, there remains a paucity of large-scale gene expression-based studies of reproductive development in species belonging to the Triticeae. As a first step to address this deficiency, a gene expression atlas of triticale reproductive development was generated using the 55K Affymetrix GeneChip(®) wheat genome array. The global transcriptional profiles of the anther/pollen, ovary and stigma were analyzed at concurrent developmental stages, and co-expressed as well as preferentially expressed genes were identified. Data analysis revealed both novel and conserved regulatory factors underlying Triticeae floral development and function. This comprehensive resource rests upon detailed gene annotations, and the expression profiles are readily accessible via a web browser. © 2013 Her Majesty the Queen in Right of Canada as represented by the Minister of Agriculture and Agri-Food Canada.

  6. [Concepts of development of the neurosurgical operative environment in the 21st century].

    PubMed

    Apuzzo, M; Liu, C

    2002-01-01

    The operative environment has to a large extent defines the "state of the art and science" of neurosurgery, which is now undergoing rapid reinvention. In order to remain current, each neurosurgeon should periodically reconsider their personal operative environment and its functional design with reference to modernity of practice as currently defined. Historical trends and their analysis offer predictive guides for development of such settings with an eye toward the future. Examination of technical developments in decade timeframes defines the progress in capability and need. Progressive minimalism of manipulation and the presence of operative definition with increasing precision are evident, with concurrent miniaturization of attendant computerized support systems, sensors, robotic interfaces, and imaging devices. These trends and developments offer the opportunity for simplificity of setting design with higher functionality as the desired endpoint.

  7. Prostate Cancer: Serum and Tissue Markers

    PubMed Central

    Miller, Gary J; Brawer, Michael K; Sakr, Wael A; Thrasher, J Brantley; Townsend, Ronald

    2001-01-01

    The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the “gold standard,” has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging. PMID:16985995

  8. Investigating Viruses during the Transformation of Molecular Biology.

    PubMed

    Moss, Bernard

    2017-03-10

    This Reflections article describes my early work on viral enzymes and the discovery of mRNA capping, how my training in medicine and biochemistry merged as I evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970s and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (VACV), a large DNA virus with about 200 genes. The reader may view this article as a work in progress, because I remain actively engaged in research at the National Institutes of Health (NIH) notwithstanding 50 memorable years there. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Quantitative phosphoproteomic analysis of early seed development in rice (Oryza sativa L.).

    PubMed

    Qiu, Jiehua; Hou, Yuxuan; Tong, Xiaohong; Wang, Yifeng; Lin, Haiyan; Liu, Qing; Zhang, Wen; Li, Zhiyong; Nallamilli, Babi R; Zhang, Jian

    2016-02-01

    Rice (Oryza sativa L.) seed serves as a major food source for over half of the global population. Though it has been long recognized that phosphorylation plays an essential role in rice seed development, the phosphorylation events and dynamics in this process remain largely unknown so far. Here, we report the first large scale identification of rice seed phosphoproteins and phosphosites by using a quantitative phosphoproteomic approach. Thorough proteomic studies in pistils and seeds at 3, 7 days after pollination resulted in the successful identification of 3885, 4313 and 4135 phosphopeptides respectively. A total of 2487 proteins were differentially phosphorylated among the three stages, including Kip related protein 1, Rice basic leucine zipper factor 1, Rice prolamin box binding factor and numerous other master regulators of rice seed development. Moreover, differentially phosphorylated proteins may be extensively involved in the biosynthesis and signaling pathways of phytohormones such as auxin, gibberellin, abscisic acid and brassinosteroid. Our results strongly indicated that protein phosphorylation is a key mechanism regulating cell proliferation and enlargement, phytohormone biosynthesis and signaling, grain filling and grain quality during rice seed development. Overall, the current study enhanced our understanding of the rice phosphoproteome and shed novel insight into the regulatory mechanism of rice seed development.

  10. Identification of Odorant-Receptor Interactions by Global Mapping of the Human Odorome

    PubMed Central

    Audouze, Karine; Tromelin, Anne; Le Bon, Anne Marie; Belloir, Christine; Petersen, Rasmus Koefoed; Kristiansen, Karsten; Brunak, Søren; Taboureau, Olivier

    2014-01-01

    The human olfactory system recognizes a broad spectrum of odorants using approximately 400 different olfactory receptors (hORs). Although significant improvements of heterologous expression systems used to study interactions between ORs and odorant molecules have been made, screening the olfactory repertoire of hORs remains a tremendous challenge. We therefore developed a chemical systems level approach based on protein-protein association network to investigate novel hOR-odorant relationships. Using this new approach, we proposed and validated new bioactivities for odorant molecules and OR2W1, OR51E1 and OR5P3. As it remains largely unknown how human perception of odorants influence or prevent diseases, we also developed an odorant-protein matrix to explore global relationships between chemicals, biological targets and disease susceptibilities. We successfully experimentally demonstrated interactions between odorants and the cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor gamma (PPARγ). Overall, these results illustrate the potential of integrative systems chemical biology to explore the impact of odorant molecules on human health, i.e. human odorome. PMID:24695519

  11. Prospect theory in the valuation of health.

    PubMed

    Moffett, Maurice L; Suarez-Almazor, Maria E

    2005-08-01

    Prospect theory is the prominent nonexpected utility theory in the estimation of health state preference scores for quality-adjusted life year calculation. Until recently, the theory was not considered to be developed to the point of implementation in economic analysis. This review focuses on the research and evidence that tests the implementation of prospect theory into health state valuation. The typical application of expected utility theory assumes that a decision maker has stable preferences under conditions of risk and uncertainty. Under prospect theory, preferences are dependent on whether the decision maker regards the outcome of a choice as a gain or loss, relative to a reference point. The conceptual preference for standard gamble utilities in the valuation of health states has led to the development of elicitation techniques. Empirical evidence using these techniques indicates that when individual preferences are elicited, a prospect theory consistent framework appears to be necessary for adequate representation of individual health utilities. The relevance of prospect theory to policy making and resource allocation remains to be established. Societal preferences may not need the same attitudes towards risks as individual preferences, and may remain largely risk neutral.

  12. Adaptive and Innate Immune Responsiveness to Borrelia burgdorferi sensu lato in Exposed Asymptomatic Children and Children with Previous Clinical Lyme Borreliosis

    PubMed Central

    Skogman, Barbro H.; Hellberg, Sandra; Ekerfelt, Christina; Jenmalm, Maria C.; Forsberg, Pia; Ludvigsson, Johnny; Bergström, Sven; Ernerudh, Jan

    2012-01-01

    Why some individuals develop clinical manifestations in Lyme borreliosis (LB) while others remain asymptomatic is largely unknown. Therefore, we wanted to investigate adaptive and innate immune responsiveness to Borrelia burgdorferi sensu lato in exposed Borrelia-antibody-positive asymptomatic children (n = 20), children with previous clinical LB (n = 24), and controls (n = 20). Blood samples were analyzed for Borrelia-specific interferon (IFN)-γ, interleukin (IL)-4, and IL-17 secretion by ELISPOT and Borrelia-induced IL-1β, IL-6, IL-10, IL-12(p70), and tumor necrosis factor (TNF) secretion by Luminex. We found no significant differences in cytokine secretion between groups, but a tendency towards an increased spontaneous secretion of IL-6 was found among children with previous clinical LB. In conclusion, the adaptive or innate immune responsiveness to Borrelia burgdorferi sensu lato was similar in Borrelia-exposed asymptomatic children and children with previous clinical LB. Thus, the immunological mechanisms of importance for eradicating the spirochete effectively without developing clinical manifestations of LB remain unknown. PMID:22190976

  13. Role of juvenile hormone and allatotropin on nutrient allocation, ovarian development and survivorship in mosquitoes

    PubMed Central

    Hernández-Martínez, Salvador; Mayoral, Jaime G.; Li, Yiping; Noriega, Fernando G.

    2009-01-01

    Teneral reserves are utilized to initiate previtellogenic ovarian development in mosquitoes. Females having emerged with low teneral reserves have reduced juvenile hormone (JH) synthesis and previtellogenic development. We investigated what role JH, allatotropin (AT) and other head-factors play in the regulation of previtellogenic ovarian development and adult survivorship. Factors from the head are essential for corpora allata (CA) activation and reproductive maturation. We have shown that decapitation of females within 9–12 h after adult ecdysis prevented normal development of the previtellogenic follicles; however maximum previtellogenic ovarian development could be induced in decapitated females by topically applying a JH analog. When females were decapitated 12 or more hours after emergence nutritional resources had been committed to ovarian development and survivorship was significantly reduced. To study if allatotropin levels correlated with teneral reserves, we measured AT titers in the heads of two adult phenotypes (large and small females) generated by raising larvae under different nutritional diets. In large mosquitoes AT levels increased to a maximum of 45 fmol in day 4; in contrast, the levels of allatotropin in the heads of small mosquitoes remained below 9 fmol during the 7 days evaluated. These results suggest that only when nutrients are appropriate, factors released from the brain induce the CA to synthesize enough JH to activate reproductive maturation. PMID:17070832

  14. Electrophysiological properties of the membrane and acetylcholine receptor in developing rat and chick myotubes

    PubMed Central

    1975-01-01

    Membrane properties of rat and chick myotubes in various stages of development were studied. Resting membrane potentials (Em) increased from -8 to -55 mV in both rat and chick as the myotubes developed from myoblasts to large multinucleated fibers. In the rat myotubes, this increase was not accompanied by significant changes in specific membrane resistivity or changes in Na+ and K+ ion distribution. Nor have we observed a significant electrogenic component to the resting Em of mature rat myotubes under normal circumstances. A progressive increase in the passive permeability of the membrane to K+ relative to Na+ ions has been observed which can account for the changes in Em with development. In contrast to the changes in the ionic selectivity of the membrane, we have found that the ionic selectivity of the ACh receptor of rat and chick myotubes remains constant during the same period of myotube development. PMID:1176950

  15. Diagnosis and treatment of polycystic ovarian syndrome in adolescents.

    PubMed

    Nicandri, Katrina F; Hoeger, Kathleen

    2012-12-01

    To review what is understood about the pathophysiology of polycystic ovarian syndrome (PCOS), the diagnostic challenges of PCOS in adolescent women, associated risk factors, as well as the best evidence-based treatment options for adolescence. Diagnosing PCOS in adolescents requires a unique set of criteria for which no single marker currently exists. Adolescents at high risk for developing the syndrome are congenital virilization, low birth weight, premature pubarche, central precocious puberty, large for gestational age girls born to overweight mothers, obesity syndromes, insulin-resistant features, and girls born to parents with PCOS, central obesity, or diabetes in whom PCOS ought to be suspected when associated with irregular menses. Insulin, hyperandrogenemia, and adipocytokines are integral players in the pathophysiology of PCOS. PCOS may be an inheritable trait; however, no gene has yet been identified. Quality of life remains a concern for young women with PCOS. Lifestyle modifications geared to prevent long-term sequelae remain the first-line treatment in conjunction with oral contraceptive pills. Identifying PCOS in adolescents remains a diagnostic dilemma, but early intervention and treatment can improve long-term health.

  16. Addressing NCDs: A unifying agenda for sustainable development.

    PubMed

    Collins, Téa; Mikkelsen, Bente; Adams, Jennifer; Chestnov, Oleg; Evans, Tim; Feigl, Andrea; Nugent, Rachel; Pablos-Mendez, Ariel; Srivanichakorn, Supattra; Webb, Douglas

    2017-10-28

    Despite the mounting evidence that they impede social and economic development, increase inequalities, and perpetuate poverty, Noncommunicable diseases (NCDs) remain largely absent from the agendas of major development assistance initiatives. In addition, fundamental changes are developing in patterns of development assistance for health, and more of the burden for fighting NCDs is being placed on domestic budgets, thus increasing pressure on the most vulnerable countries. The paper argues, however, that a new day is coming. With the inclusion of NCDs and related targets in the 2030 Agenda for Sustainable Development, there is an unprecedented opportunity to explore linkages among the sustainable development goals, enhance policy coherence and advance the NCD agenda as part of sustainable development. International development partners (bilateral and multilateral) can help in this important effort to address NCDs and their shared risk factors by providing catalytic support to countries that are particularly vulnerable in terms of the disease burden but lack the resources (human, financial) and institutional arrangements to meet their commitments at national, regional, and global levels.

  17. A Spur to Atavism: Placing Platypus Poison.

    PubMed

    Hobbins, Peter

    2015-11-01

    For over two centuries, the platypus (Ornithorhynchus anatinus) has been constructed and categorized in multiple ways. An unprecedented mélange of anatomical features and physiological functions, it long remained a systematic quandary. Nevertheless, since 1797, naturalists and biologists have pursued two recurring obsessions. Investigations into platypus reproduction and lactation have focused attention largely upon females of the species. Despite its apparent admixture of avian, reptilian and mammalian characters, the platypus was soon placed as a rudimentary mammal--primitive, naïve and harmless. This article pursues a different taxonomic trajectory, concentrating on a specifically male anatomical development: the crural spur and venom gland on the hind legs. Once the defining characteristic of both the platypus and echidna (Tachyglossus aculeatus), by 1830 this sexed spur had been largely dismissed as inactive and irrelevant. For a creature regularly depicted as a biological outlier, the systematic and evolutionary implications of platypus poison have remained largely overlooked. In Australia, however, sporadic cases of 'spiking' led to consistent homologies being remarked between the platypus crural system and the venom glands of snakes. As with its reproductive reliance upon eggs, possession of an endogenous poison suggested significant reptilian affinities, yet the platypus has rarely been classed as an advanced reptile. Indeed, ongoing uncertainty regarding the biological purpose of the male's spur has ostensibly posed a directional puzzle. As with so many of its traits, however, platypus poison has been consistently described as a redundant remnant, rather than an emergent feature indicating evolutionary advance.

  18. Source-gated transistors for order-of-magnitude performance improvements in thin-film digital circuits

    NASA Astrophysics Data System (ADS)

    Sporea, R. A.; Trainor, M. J.; Young, N. D.; Shannon, J. M.; Silva, S. R. P.

    2014-03-01

    Ultra-large-scale integrated (ULSI) circuits have benefited from successive refinements in device architecture for enormous improvements in speed, power efficiency and areal density. In large-area electronics (LAE), however, the basic building-block, the thin-film field-effect transistor (TFT) has largely remained static. Now, a device concept with fundamentally different operation, the source-gated transistor (SGT) opens the possibility of unprecedented functionality in future low-cost LAE. With its simple structure and operational characteristics of low saturation voltage, stability under electrical stress and large intrinsic gain, the SGT is ideally suited for LAE analog applications. Here, we show using measurements on polysilicon devices that these characteristics lead to substantial improvements in gain, noise margin, power-delay product and overall circuit robustness in digital SGT-based designs. These findings have far-reaching consequences, as LAE will form the technological basis for a variety of future developments in the biomedical, civil engineering, remote sensing, artificial skin areas, as well as wearable and ubiquitous computing, or lightweight applications for space exploration.

  19. Source-gated transistors for order-of-magnitude performance improvements in thin-film digital circuits

    PubMed Central

    Sporea, R. A.; Trainor, M. J.; Young, N. D.; Shannon, J. M.; Silva, S. R. P.

    2014-01-01

    Ultra-large-scale integrated (ULSI) circuits have benefited from successive refinements in device architecture for enormous improvements in speed, power efficiency and areal density. In large-area electronics (LAE), however, the basic building-block, the thin-film field-effect transistor (TFT) has largely remained static. Now, a device concept with fundamentally different operation, the source-gated transistor (SGT) opens the possibility of unprecedented functionality in future low-cost LAE. With its simple structure and operational characteristics of low saturation voltage, stability under electrical stress and large intrinsic gain, the SGT is ideally suited for LAE analog applications. Here, we show using measurements on polysilicon devices that these characteristics lead to substantial improvements in gain, noise margin, power-delay product and overall circuit robustness in digital SGT-based designs. These findings have far-reaching consequences, as LAE will form the technological basis for a variety of future developments in the biomedical, civil engineering, remote sensing, artificial skin areas, as well as wearable and ubiquitous computing, or lightweight applications for space exploration. PMID:24599023

  20. Widespread mechanosensing controls the structure behind the architecture in plants.

    PubMed

    Hamant, Olivier

    2013-10-01

    Mechanical forces play an instructing role for many aspects of animal cell biology, such as division, polarity and fate. Although the associated mechanoperception pathways still remain largely elusive in plants, physical cues have long been thought to guide development in parallel to biochemical factors. With the development of new imaging techniques, micromechanics tools and modeling approaches, the role of mechanical signals in plant development is now re-examined and fully integrated with modern cell biology. Using recent examples from the literature, I propose to use a multiscale perspective, from the whole plant down to the cell wall, to fully appreciate the diversity of developmental processes that depend on mechanical signals. Incidentally, this also illustrates how conceptually rich this field is. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Telemedicine: lessons remain unheeded.

    PubMed Central

    McLaren, P.; Ball, C. J.

    1995-01-01

    Telemedicine, the delivery of health care with the patient and health professional at different locations, has been around for over 30 years. Its driving force has been developments in communications technology, and as new communications systems are developed health applications are proposed such as supporting the delivery of primary health care to geographically remote areas or regions underserved through the maldistribution of professional expertise. Despite rapid technological advances, evaluations of such systems have been largely superficial, and more thorough evaluations have failed to show significant advantages for more advanced and expensive technology over older technology such as the telephone. Methods for evaluating the impact of particular technologies on the health care system need to be developed and clearer benefits shown in terms of improved standards of care. Images p1391-a PMID:7787547

  2. Prey size and availability limits maximum size of rainbow trout in a large tailwater: insights from a drift-foraging bioenergetics model

    USGS Publications Warehouse

    Dodrill, Michael J.; Yackulic, Charles B.; Kennedy, Theodore A.; Haye, John W

    2016-01-01

    The cold and clear water conditions present below many large dams create ideal conditions for the development of economically important salmonid fisheries. Many of these tailwater fisheries have experienced declines in the abundance and condition of large trout species, yet the causes of these declines remain uncertain. Here, we develop, assess, and apply a drift-foraging bioenergetics model to identify the factors limiting rainbow trout (Oncorhynchus mykiss) growth in a large tailwater. We explored the relative importance of temperature, prey quantity, and prey size by constructing scenarios where these variables, both singly and in combination, were altered. Predicted growth matched empirical mass-at-age estimates, particularly for younger ages, demonstrating that the model accurately describes how current temperature and prey conditions interact to determine rainbow trout growth. Modeling scenarios that artificially inflated prey size and abundance demonstrate that rainbow trout growth is limited by the scarcity of large prey items and overall prey availability. For example, shifting 10% of the prey biomass to the 13 mm (large) length class, without increasing overall prey biomass, increased lifetime maximum mass of rainbow trout by 88%. Additionally, warmer temperatures resulted in lower predicted growth at current and lower levels of prey availability; however, growth was similar across all temperatures at higher levels of prey availability. Climate change will likely alter flow and temperature regimes in large rivers with corresponding changes to invertebrate prey resources used by fish. Broader application of drift-foraging bioenergetics models to build a mechanistic understanding of how changes to habitat conditions and prey resources affect growth of salmonids will benefit management of tailwater fisheries.

  3. The emergence and outbreak of multidrug-resistant typhoid fever in China.

    PubMed

    Yan, Meiying; Li, Xinlan; Liao, Qiaohong; Li, Fang; Zhang, Jing; Kan, Biao

    2016-06-22

    Typhoid fever remains a severe public health problem in developing countries. The emergence of resistant typhoid, particularly multidrug-resistant typhoid infections, highlights the necessity of monitoring the resistance characteristics of this invasive pathogen. In this study, we report a typhoid fever outbreak caused by multidrug-resistant Salmonella enterica serovar Typhi strains with an ACSSxtT pattern. Resistance genes conferring these phenotypes were harbored by a large conjugative plasmid, which increases the threat of Salmonella Typhi and thus requires close surveillance for dissemination of strains containing such genes.

  4. Trichuris suis ova in inflammatory bowel disease.

    PubMed

    Schölmerich, Jürgen

    2013-01-01

    Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.

  5. The emergence and outbreak of multidrug-resistant typhoid fever in China

    PubMed Central

    Yan, Meiying; Li, Xinlan; Liao, Qiaohong; Li, Fang; Zhang, Jing; Kan, Biao

    2016-01-01

    Typhoid fever remains a severe public health problem in developing countries. The emergence of resistant typhoid, particularly multidrug-resistant typhoid infections, highlights the necessity of monitoring the resistance characteristics of this invasive pathogen. In this study, we report a typhoid fever outbreak caused by multidrug-resistant Salmonella enterica serovar Typhi strains with an ACSSxtT pattern. Resistance genes conferring these phenotypes were harbored by a large conjugative plasmid, which increases the threat of Salmonella Typhi and thus requires close surveillance for dissemination of strains containing such genes. PMID:27329848

  6. Challenges and opportunities in synthetic biology for chemical engineers

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

    Luo, YZ; Lee, JK; Zhao, HM

    Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. (C) 2012 Elsevier Ltd. All rights reserved.

  7. Hand hygiene promotion and the participation of infection control link nurses: an effective innovation to overcome campaign fatigue.

    PubMed

    Seto, Wing Hong; Yuen, Shanny W S; Cheung, Christina W Y; Ching, Patricia T Y; Cowling, Benjamin J; Pittet, Didier

    2013-12-01

    Campaign fatigue was evident in a large hospital in Hong Kong when hand hygiene compliance remained just above 50% after 4 years of aggressive and varied promotional activities. A new innovative strategy was developed that directly involved the infection control link nurses both in formulating the strategy and in implementing the various proposed programs. The new strategy was successful in increasing hand hygiene compliance to 83%. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  8. Determination of functional collective motions in a protein at atomic resolution using coherent neutron scattering

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

    Hong, Liang; Jain, Nitin; Cheng, Xiaolin

    Protein function often depends on global, collective internal motions. However, the simultaneous quantitative experimental determination of the forms, amplitudes, and time scales of these motions has remained elusive. We demonstrate that a complete description of these large-scale dynamic modes can be obtained using coherent neutron-scattering experiments on perdeuterated samples. With this approach, a microscopic relationship between the structure, dynamics, and function in a protein, cytochrome P450cam, is established. The approach developed here should be of general applicability to protein systems.

  9. Adaptive management of social-ecological systems: the path forward

    USGS Publications Warehouse

    Allen, Craig R.

    2015-01-01

    Adaptive management remains at the forefront of environmental management nearly 40 years after its original conception, largely because we have yet to develop other methodologies that offer the same promise. Despite the criticisms of adaptive management and the numerous failed attempts to implement it, adaptive management has yet to be replaced with a better alternative. The concept persists because it is simple, allows action despite uncertainty, and fosters learning. Moving forward, adaptive management of social-ecological systems provides policymakers, managers and scientists a powerful tool for managing for resilience in the face of uncertainty.

  10. Determination of functional collective motions in a protein at atomic resolution using coherent neutron scattering

    DOE PAGES

    Hong, Liang; Jain, Nitin; Cheng, Xiaolin; ...

    2016-10-14

    Protein function often depends on global, collective internal motions. However, the simultaneous quantitative experimental determination of the forms, amplitudes, and time scales of these motions has remained elusive. We demonstrate that a complete description of these large-scale dynamic modes can be obtained using coherent neutron-scattering experiments on perdeuterated samples. With this approach, a microscopic relationship between the structure, dynamics, and function in a protein, cytochrome P450cam, is established. The approach developed here should be of general applicability to protein systems.

  11. Unprovoked Pulmonary Embolism in a Young Patient with Marfan Syndrome.

    PubMed

    Pak, Stella; Kilgore, Andrew; Thornhill, Rosanne; Rako, Kyle; Meier, Ali; Pora, Gavriella; Costello, Jillian M; Dee, Christine

    2017-09-05

    Marfan syndrome is a rare connective tissue disorder with a prevalence of approximately 2 to 3 per 10,000 individuals. There have been some reports of young patients with Marfan syndrome developing arteriovenous thromboembolism. These events were unprovoked and recurrent. Owing to its rarity, hypercoagulopathy and other metabolic derangement in patients with Marfan syndrome remains largely unknown. Herein, we report a case of a young man with Marfan syndrome who had myocardial infarction and pulmonary embolism. We hope that this case adds to the scant body of knowledge about this patient population.

  12. Challenges and opportunities in synthetic biology for chemical engineers

    PubMed Central

    Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

    2012-01-01

    Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. PMID:24222925

  13. Challenges and opportunities in synthetic biology for chemical engineers.

    PubMed

    Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

    2013-11-15

    Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement.

  14. Brucellosis update in Libya and regional prospective

    PubMed Central

    Ahmed, Mohamed O; Abouzeed, Yousef M; Bennour, Emad M; van Velkinburgh, Jennifer C

    2015-01-01

    Brucellosis is a global bacterial zoonosis responsible for high morbidity in humans and significant livestock economic losses. While brucellosis remains a public health concern worldwide, its global geographic distribution is variable, largely due to different management schemes; however, paucity of information renders the status of brucellosis unclear and incomplete in many countries, especially those with low income and under-developed infrastructure. This short article summarizes and discusses recent important updates on brucellosis from the North African countries, with a particular brief emphasis on the current status and recent updates in Libya. PMID:25578285

  15. Brucellosis update in Libya and regional prospective.

    PubMed

    Ahmed, Mohamed O; Abouzeed, Yousef M; Bennour, Emad M; van Velkinburgh, Jennifer C

    2015-02-01

    Brucellosis is a global bacterial zoonosis responsible for high morbidity in humans and significant livestock economic losses. While brucellosis remains a public health concern worldwide, its global geographic distribution is variable, largely due to different management schemes; however, paucity of information renders the status of brucellosis unclear and incomplete in many countries, especially those with low income and under-developed infrastructure. This short article summarizes and discusses recent important updates on brucellosis from the North African countries, with a particular brief emphasis on the current status and recent updates in Libya.

  16. Photo-induced toxic epidermal necrolysis caused by clobazam.

    PubMed

    Redondo, P; Vicente, J; España, A; Subira, M L; De Felipe, I; Quintanilla, E

    1996-12-01

    Toxic epidermal necrolysis (TEN) is a life-threatening disease, the pathogenesis of which remains largely unknown. We describe a 23-year-old woman under treatment with clobazam who developed lesions of TEN in light-exposed areas. Patch and photopatch tests with clobazam were negative. The cellular phenotype and cytokines were studied in blister fluid. The cellular infiltrate was composed mainly of T lymphocytes with a predominant cytotoxic phenotype. There was an increase in the level of tumour necrosis factor (TNF)-alpha in blister fluid compared with the control (a patient with bullous pemphigoid).

  17. Enabling systematic interrogation of protein-protein interactions in live cells with a versatile ultra-high-throughput biosensor platform | Office of Cancer Genomics

    Cancer.gov

    The vast datasets generated by next generation gene sequencing and expression profiling have transformed biological and translational research. However, technologies to produce large-scale functional genomics datasets, such as high-throughput detection of protein-protein interactions (PPIs), are still in early development. While a number of powerful technologies have been employed to detect PPIs, a singular PPI biosensor platform featured with both high sensitivity and robustness in a mammalian cell environment remains to be established.

  18. The Clawpack Community of Codes

    NASA Astrophysics Data System (ADS)

    Mandli, K. T.; LeVeque, R. J.; Ketcheson, D.; Ahmadia, A. J.

    2014-12-01

    Clawpack, the Conservation Laws Package, has long been one of the standards for solving hyperbolic conservation laws but over the years has extended well beyond this role. Today a community of open-source codes have been developed that address a multitude of different needs including non-conservative balance laws, high-order accurate methods, and parallelism while remaining extensible and easy to use, largely by the judicious use of Python and the original Fortran codes that it wraps. This talk will present some of the recent developments in projects under the Clawpack umbrella, notably the GeoClaw and PyClaw projects. GeoClaw was originally developed as a tool for simulating tsunamis using adaptive mesh refinement but has since encompassed a large number of other geophysically relevant flows including storm surge and debris-flows. PyClaw originated as a Python version of the original Clawpack algorithms but has since been both a testing ground for new algorithmic advances in the Clawpack framework but also an easily extensible framework for solving hyperbolic balance laws. Some of these extensions include the addition of WENO high-order methods, massively parallel capabilities, and adaptive mesh refinement technologies, made possible largely by the flexibility of the Python language and community libraries such as NumPy and PETSc. Because of the tight integration with Python tecnologies, both packages have benefited also from the focus on reproducibility in the Python community, notably IPython notebooks.

  19. Pressure fluctuations beneath turbulent spots and instability wave packets in a hypersonic boundary layer.

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

    Beresh, Steven Jay; Casper, Katya M.; Schneider, Steven P.

    2010-12-01

    The development of turbulent spots in a hypersonic boundary layer was studied on the nozzle wall of the Boeing/AFOSR Mach-6 Quiet Tunnel. Under quiet flow conditions, the nozzle wall boundary layer remains laminar and grows very thick over the long nozzle length. This allows the development of large turbulent spots that can be readily measured with pressure transducers. Measurements of naturally occurring wave packets and developing turbulent spots were made. The peak frequencies of these natural wave packets were in agreement with second-mode computations. For a controlled study, the breakdown of disturbances created by spark and glow perturbations were studiedmore » at similar freestream conditions. The spark perturbations were the most effective at creating large wave packets that broke down into turbulent spots. The flow disturbances created by the controlled perturbations were analyzed to obtain amplitude criteria for nonlinearity and breakdown as well as the convection velocities of the turbulent spots. Disturbances first grew into linear instability waves and then quickly became nonlinear. Throughout the nonlinear growth of the wave packets, large harmonics are visible in the power spectra. As breakdown begins, the peak amplitudes of the instability waves and harmonics decrease into the rising broad-band frequencies. Instability waves are still visible on either side of the growing turbulent spots during this breakdown process.« less

  20. Threats to intact tropical peatlands and opportunities for their conservation.

    PubMed

    Roucoux, K H; Lawson, I T; Baker, T R; Del Castillo Torres, D; Draper, F C; Lähteenoja, O; Gilmore, M P; Honorio Coronado, E N; Kelly, T J; Mitchard, E T A; Vriesendorp, C F

    2017-12-01

    Large, intact areas of tropical peatland are highly threatened at a global scale by the expansion of commercial agriculture and other forms of economic development. Conserving peatlands on a landscape scale, with their hydrology intact, is of international conservation importance to preserve their distinctive biodiversity and ecosystem services and maintain their resilience to future environmental change. We explored threats to and opportunities for conserving remaining intact tropical peatlands; thus, we excluded peatlands of Indonesia and Malaysia, where extensive deforestation, drainage, and conversion to plantations means conservation in this region can protect only small fragments of the original ecosystem. We focused on a case study, the Pastaza-Marañón Foreland Basin (PMFB) in Peru, which is among the largest known intact tropical peatland landscapes in the world and is representative of peatland vulnerability. Maintenance of the hydrological conditions critical for carbon storage and ecosystem function of peatlands is, in the PMFB, primarily threatened by expansion of commercial agriculture linked to new transport infrastructure that is facilitating access to remote areas. There remain opportunities in the PMFB and elsewhere to develop alternative, more sustainable land-use practices. Although some of the peatlands in the PMFB fall within existing legally protected areas, this protection does not include the most carbon-dense (domed pole forest) areas. New carbon-based conservation instruments (e.g., REDD+, Green Climate Fund), developing markets for sustainable peatland products, transferring land title to local communities, and expanding protected areas offer pathways to increased protection for intact tropical peatlands in Amazonia and elsewhere, such as those in New Guinea and Central Africa which remain, for the moment, broadly beyond the frontier of commercial development. © 2017 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

  1. Genetic identification of missing persons: DNA analysis of human remains and compromised samples.

    PubMed

    Alvarez-Cubero, M J; Saiz, M; Martinez-Gonzalez, L J; Alvarez, J C; Eisenberg, A J; Budowle, B; Lorente, J A

    2012-01-01

    Human identification has made great strides over the past 2 decades due to the advent of DNA typing. Forensic DNA typing provides genetic data from a variety of materials and individuals, and is applied to many important issues that confront society. Part of the success of DNA typing is the generation of DNA databases to help identify missing persons and to develop investigative leads to assist law enforcement. DNA databases house DNA profiles from convicted felons (and in some jurisdictions arrestees), forensic evidence, human remains, and direct and family reference samples of missing persons. These databases are essential tools, which are becoming quite large (for example the US Database contains 10 million profiles). The scientific, governmental and private communities continue to work together to standardize genetic markers for more effective worldwide data sharing, to develop and validate robust DNA typing kits that contain the reagents necessary to type core identity genetic markers, to develop technologies that facilitate a number of analytical processes and to develop policies to make human identity testing more effective. Indeed, DNA typing is integral to resolving a number of serious criminal and civil concerns, such as solving missing person cases and identifying victims of mass disasters and children who may have been victims of human trafficking, and provides information for historical studies. As more refined capabilities are still required, novel approaches are being sought, such as genetic testing by next-generation sequencing, mass spectrometry, chip arrays and pyrosequencing. Single nucleotide polymorphisms offer the potential to analyze severely compromised biological samples, to determine the facial phenotype of decomposed human remains and to predict the bioancestry of individuals, a new focus in analyzing this type of markers. Copyright © 2012 S. Karger AG, Basel.

  2. Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and Hub Regulatory Genes of Large Intestinal Lipid Metabolism.

    PubMed

    Chao, Tianle; Wang, Guizhi; Ji, Zhibin; Liu, Zhaohua; Hou, Lei; Wang, Jin; Wang, Jianmin

    2017-07-13

    The large intestine, also known as the hindgut, is an important part of the animal digestive system. Recent studies on digestive system development in ruminants have focused on the rumen and the small intestine, but the molecular mechanisms underlying sheep large intestine metabolism remain poorly understood. To identify genes related to intestinal metabolism and to reveal molecular regulation mechanisms, we sequenced and compared the transcriptomes of mucosal epithelial tissues among the cecum, proximal colon and duodenum. A total of 4,221 transcripts from 3,254 genes were identified as differentially expressed transcripts. Between the large intestine and duodenum, differentially expressed transcripts were found to be significantly enriched in 6 metabolism-related pathways, among which PPAR signaling was identified as a key pathway. Three genes, CPT1A, LPL and PCK1, were identified as higher expression hub genes in the large intestine. Between the cecum and colon, differentially expressed transcripts were significantly enriched in 5 lipid metabolism related pathways, and CEPT1 and MBOAT1 were identified as hub genes. This study provides important information regarding the molecular mechanisms of intestinal metabolism in sheep and may provide a basis for further study.

  3. A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

    PubMed

    Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

    2016-03-21

    Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. A Puzzle Assembly Strategy for Fabrication of Large Engineered Cartilage Tissue Constructs

    PubMed Central

    Nover, Adam B.; Jones, Brian K.; Yu, William T.; Donovan, Daniel S.; Podolnick, Jeremy D.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

    2016-01-01

    Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID:26895780

  5. Association between large strongyle genera in larval cultures--using rare-event poisson regression.

    PubMed

    Cao, X; Vidyashankar, A N; Nielsen, M K

    2013-09-01

    Decades of intensive anthelmintic treatment has caused equine large strongyles to become quite rare, while the cyathostomins have developed resistance to several drug classes. The larval culture has been associated with low to moderate negative predictive values for detecting Strongylus vulgaris infection. It is unknown whether detection of other large strongyle species can be statistically associated with presence of S. vulgaris. This remains a statistical challenge because of the rare occurrence of large strongyle species. This study used a modified Poisson regression to analyse a dataset for associations between S. vulgaris infection and simultaneous occurrence of Strongylus edentatus and Triodontophorus spp. In 663 horses on 42 Danish farms, the individual prevalences of S. vulgaris, S. edentatus and Triodontophorus spp. were 12%, 3% and 12%, respectively. Both S. edentatus and Triodontophorus spp. were significantly associated with S. vulgaris infection with relative risks above 1. Further, S. edentatus was associated with use of selective therapy on the farms, as well as negatively associated with anthelmintic treatment carried out within 6 months prior to the study. The findings illustrate that occurrence of S. vulgaris in larval cultures can be interpreted as indicative of other large strongyles being likely to be present.

  6. A simple model of intraseasonal oscillations

    NASA Astrophysics Data System (ADS)

    Fuchs, Željka; Raymond, David J.

    2017-06-01

    The intraseasonal oscillations and in particular the MJO have been and still remain a "holy grail" of today's atmospheric science research. Why does the MJO propagate eastward? What makes it unstable? What is the scaling for the MJO, i.e., why does it prefer long wavelengths or planetary wave numbers 1-3? What is the westward moving component of the intraseasonal oscillation? Though linear WISHE has long been discounted as a plausible model for intraseasonal oscillations and the MJO, the version we have developed explains many of the observed features of those phenomena, in particular, the preference for large zonal scale. In this model version, the moisture budget and the increase of precipitation with tropospheric humidity lead to a "moisture mode." The destabilization of the large-scale moisture mode occurs via WISHE only and there is no need to postulate large-scale radiatively induced instability or negative effective gross moist stability. Our WISHE-moisture theory leads to a large-scale unstable eastward propagating mode in n = -1 case and a large-scale unstable westward propagating mode in n = 1 case. We suggest that the n = -1 case might be connected to the MJO and the observed westward moving disturbance to the observed equatorial Rossby mode.

  7. Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

    PubMed Central

    Cook, Brian L.; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P.; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

    2009-01-01

    Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be ≈50% α-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices. PMID:19581598

  8. Local Helioseismology of Emerging Active Regions: A Case Study

    NASA Astrophysics Data System (ADS)

    Kosovichev, Alexander G.; Zhao, Junwei; Ilonidis, Stathis

    2018-04-01

    Local helioseismology provides a unique opportunity to investigate the subsurface structure and dynamics of active regions and their effect on the large-scale flows and global circulation of the Sun. We use measurements of plasma flows in the upper convection zone, provided by the Time-Distance Helioseismology Pipeline developed for analysis of solar oscillation data obtained by Helioseismic and Magnetic Imager (HMI) on Solar Dynamics Observatory (SDO), to investigate the subsurface dynamics of emerging active region NOAA 11726. The active region emergence was detected in deep layers of the convection zone about 12 hours before the first bipolar magnetic structure appeared on the surface, and 2 days before the emergence of most of the magnetic flux. The speed of emergence determined by tracking the flow divergence with depth is about 1.4 km/s, very close to the emergence speed in the deep layers. As the emerging magnetic flux becomes concentrated in sunspots local converging flows are observed beneath the forming sunspots. These flows are most prominent in the depth range 1-3 Mm, and remain converging after the formation process is completed. On the larger scale converging flows around active region appear as a diversion of the zonal shearing flows towards the active region, accompanied by formation of a large-scale vortex structure. This process occurs when a substantial amount of the magnetic flux emerged on the surface, and the converging flow pattern remains stable during the following evolution of the active region. The Carrington synoptic flow maps show that the large-scale subsurface inflows are typical for active regions. In the deeper layers (10-13 Mm) the flows become diverging, and surprisingly strong beneath some active regions. In addition, the synoptic maps reveal a complex evolving pattern of large-scale flows on the scale much larger than supergranulation

  9. Large-scale production and study of a synthetic G protein-coupled receptor: human olfactory receptor 17-4.

    PubMed

    Cook, Brian L; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

    2009-07-21

    Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be approximately 50% alpha-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices.

  10. Landowner Attitudes and Perceptions of Impact from Wind and Natural Gas Development in Northern Pennsylvania: Implications for Energy Landscapes in Rural America

    NASA Astrophysics Data System (ADS)

    Jacquet, Jeffrey Bryan

    Energy developments such as industrial scale wind farms and unconventional natural gas drilling represent some of the largest and most controversial land use changes occurring in the United States today. A diverse array of academic disciplines have each sought to explain the social, psychological, and economic effects of siting large industrial facilities in rural areas, however the research has largely remained discipline-specific. This study measures resident attitudes and perceptions of impact from both wind and gas drilling occurring simultaneously in the Armenia Mountain Area of northern Pennsylvania. The results of a mail survey of landowners (n = 1028) in this study area reveal factors that explain landowner variation in attitudes and perception of impact, and describe new forms of participation in the planning and siting of these energy projects. Direction is provided for a new and synthetic theoretical understanding of how residents perceive these impacts and impacts from land use change. The work advances “risk of social and psychological disruption” as a key factor that may influence how residents respond to the prospect of large land use changes. Implications for the regulation and planning of these energy sources are offered, including a new understanding of how landowners participate in the planning and siting of large energy projects. Finally, the limitations of this work, as well as opportunities and implications for future research, are discussed.

  11. Large wood dynamics and biophysical consequences for riparian forests: A comparison of an unconfined alluvial river in a temperate rainforest and a bedrock confined river in a semi-arid South African savanna.

    NASA Astrophysics Data System (ADS)

    Latterell, J. J.; Pettit, N. E.; Naiman, R. J.

    2005-05-01

    Large wood shapes the geomorphology and ecology of rivers. We determined the origin, distribution, and fate of large wood in two rivers from contrasting environments. The Queets is an unstable temperate, rainforest river running from the Olympic Mountains (USA) through a glacial valley with colossal trees. In most years, the channel erodes a variety of forested landforms which forms jams that sculpt habitats. Many are displaced in a few years. Remaining jams initiate landform development and forest renewal. Thus, wood is stockpiled in the floodplain where it may become buried. Channel movements recapture most logs within 50 years. In contrast, the Sabie is a perennial river running through a confined bedrock channel in a fire-prone semi-arid South African savanna. Riparian trees are relatively small and many sink in water. A recent flood (February 2000) devastated the riparian forest, introducing wood to the channel. Jams formed on toppled trees, transported logs, and bedrock outcrops. Many trees survived and resprouted. Jams facilitated the establishment of woody plant seedlings and the intrusion of fire into riparian areas. Sunken wood formed unique depositional features. The Queets and Sabie rivers are strikingly different systems. However, large wood appears to promote the renewal and development of complex riparian forests in both rivers.

  12. Towards Large-area Field-scale Operational Evapotranspiration for Water Use Mapping

    NASA Astrophysics Data System (ADS)

    Senay, G. B.; Friedrichs, M.; Morton, C.; Huntington, J. L.; Verdin, J.

    2017-12-01

    Field-scale evapotranspiration (ET) estimates are needed for improving surface and groundwater use and water budget studies. Ideally, field-scale ET estimates would be at regional to national levels and cover long time periods. As a result of large data storage and computational requirements associated with processing field-scale satellite imagery such as Landsat, numerous challenges remain to develop operational ET estimates over large areas for detailed water use and availability studies. However, the combination of new science, data availability, and cloud computing technology is enabling unprecedented capabilities for ET mapping. To demonstrate this capability, we used Google's Earth Engine cloud computing platform to create nationwide annual ET estimates with 30-meter resolution Landsat ( 16,000 images) and gridded weather data using the Operational Simplified Surface Energy Balance (SSEBop) model in support of the National Water Census, a USGS research program designed to build decision support capacity for water management agencies and other natural resource managers. By leveraging Google's Earth Engine Application Programming Interface (API) and developing software in a collaborative, open-platform environment, we rapidly advance from research towards applications for large-area field-scale ET mapping. Cloud computing of the Landsat image archive combined with other satellite, climate, and weather data, is creating never imagined opportunities for assessing ET model behavior and uncertainty, and ultimately providing the ability for more robust operational monitoring and assessment of water use at field-scales.

  13. Catalog of total excitation-emission and total synchronous fluorescence maps with synchronous fluorescence spectra of homologated fluorescent pesticides in large use in Morocco: development of a spectrometric low cost and direct analysis as an alert method in case of massive contamination of soils and waters by fluorescent pesticides.

    PubMed

    Foudeil, S; Hassoun, H; Lamhasni, T; Ait Lyazidi, S; Benyaich, F; Haddad, M; Choukrad, M; Boughdad, A; Bounakhla, M; Bounouira, H; Duarte, R M B O; Cachada, A; Duarte, A C

    2015-05-01

    The purpose of this research is to develop a direct spectrometric approach to monitor soils and waters, at a lower cost than the widely used chromatographic techniques; a spectrometric approach that is effective, reliable, fast, easy to implement, and without any use of organic solvents whose utilization is subject to law limitation. It could be suitable at least as an alert method in case of massive contamination. Here, we present for the first time a catalog of excitation-emission and total synchronous fluorescence maps that may be considered as fingerprints of a series of homologated pesticides, in large use in Morocco, aiming at a direct detection of their remains in agricultural soils and neighboring waters. After a large survey among farmers, agricultural workers and product distributors in two important agricultural regions of Morocco (Doukkala-Abda and Sebou basin), 48 commercial pesticides, which are fluorescent, were chosen. A multi-component spectral database of these targeted commercial pesticides was elaborated. For each pesticide, dissolved in water at the lowest concentration giving a no-noise fluorescence spectrum, the total excitation-emission matrix (TEEM), the total synchronous fluorescence matrix (TSFM) in addition to synchronous fluorescence spectra (SFS) at those offsets giving the highest fluorescence intensity were recorded. To test this preliminary multi-component database, two real soil samples, collected at a wheat field and at a vine field in the region of Doukkala, were analyzed. Remains of the commercial Pirimor (Carbamate) and Atlantis (Sulfonylurea) were identified by comparison of the recorded TEEM, TSFM, and SFS to those of the preliminary catalog at one hand, and on the basis of the results of a field pre-survey. The developed approach seems satisfactory, and the fluorimetric fingerprint database is under extension to a higher number of fluorescent pesticides in common use among the Moroccan agricultural regions.

  14. Assessing levels and trends of child health inequality in 88 developing countries: from 2000 to 2014

    PubMed Central

    Li, Zhihui; Li, Mingqiang; Subramanian, S. V.; Lu, Chunling

    2017-01-01

    ABSTRACT Background: Reducing child mortality was one of the Millennium Development Goals. In the current Sustainable Development Goals era, achieving equity is prioritized as a major aim. Objective: This study aims to provide a comprehensive and updated picture of inequalities in child health intervention coverage and child health outcomes by wealth status, as well as their trends between 2000 and 2014. Methods: Using data from Demographic Health Surveys and Multiple Indicator Cluster Surveys, we adopted three measures of inequality, including one absolute inequality indicator and two relative inequality indicators, to estimate the level and trends of inequalities in three child health outcome variables and 17 intervention coverages in 88 developing countries. Results: While improvements in child health outcomes and coverage of interventions have been observed between 2000 and 2014, large inequalities remain. There was a high level of variation between countries’ progress toward reducing child health inequalities, with some countries significantly improving, some deteriorating, and some remaining statistically unchanged. Among child health interventions, the least equitable one was access to improved sanitation (The absolute difference in coverages between the richest quintile and the poorest quintile reached 49.5% [42.7, 56.2]), followed by access to improved water (34.1% [29.5, 38.6]), and skilled birth attendant (SBA) (34.1% [28.8, 39.4]). The most equitable intervention coverage was insecticide-treated bed net for children (1.0% [−3.9, 5.9]), followed by oral rehydration therapy for diarrhea ((8.0% [5.2, 10.8]), and vitamin A supplement (8.4% [5.1, 11.7]). These findings were robust to various inequality measurements. Conclusions: Although child health outcomes and coverage of interventions have improved largely over the study period for almost all wealth quintiles, insufficient progress was made in reducing child health inequalities between the poorest and richest wealth quintiles. Future efforts should focus on reaching the poorest children by increasing investments toward expanding the coverage of interventions in resource-limited settings. PMID:29228888

  15. The plasma separation process as a pre-cursor for large scale radioisotope production

    NASA Astrophysics Data System (ADS)

    Stevenson, Nigel R.

    2001-07-01

    Radioisotope production generally employs either accelerators or reactors to convert stable (usually enriched) isotopes into the desired product species. Radioisotopes have applications in industry, environmental sciences, and most significantly in medicine. The production of many potentially useful radioisotopes is significantly hindered by the lack of availability or by the high cost of key enriched stable isotopes. To try and meet this demand, certain niche enrichment processes have been developed and commercialized. Calutrons, centrifuges, and laser separation processes are some of the devices and techniques being employed to produce large quantities of selective enriched stable isotopes. Nevertheless, the list of enriched stable isotopes in sufficient quantities remains rather limited and this continues to restrict the availability of many radioisotopes that otherwise could have a significant impact on society. The Plasma Separation Process is a newly available commercial technique for producing large quantities of a wide range of enriched isotopes and thereby holds promise of being able to open the door to producing new and exciting applications of radioisotopes in the future.

  16. Why large porphyry Cu deposits like high Sr/Y magmas?

    PubMed Central

    Chiaradia, Massimo; Ulianov, Alexey; Kouzmanov, Kalin; Beate, Bernardo

    2012-01-01

    Porphyry systems supply most copper and significant gold to our economy. Recent studies indicate that they are frequently associated with high Sr/Y magmatic rocks, but the meaning of this association remains elusive. Understanding the association between high Sr/Y magmatic rocks and porphyry-type deposits is essential to develop genetic models that can be used for exploration purposes. Here we present results on a Pleistocene volcano of Ecuador that highlight the behaviour of copper in magmas with variable (but generally high) Sr/Y values. We provide indirect evidence for Cu partitioning into a fluid phase exsolved at depths of ~15 km from high Sr/Y (>70) andesitic magmas before sulphide saturation. This lends support to the hypothesis that large amounts of Cu- and S-bearing fluids can be accumulated into and released from a long-lived high Sr/Y deep andesitic reservoir to a shallower magmatic-hydrothermal system with the potential of generating large porphyry-type deposits. PMID:23008750

  17. Why large porphyry Cu deposits like high Sr/Y magmas?

    PubMed

    Chiaradia, Massimo; Ulianov, Alexey; Kouzmanov, Kalin; Beate, Bernardo

    2012-01-01

    Porphyry systems supply most copper and significant gold to our economy. Recent studies indicate that they are frequently associated with high Sr/Y magmatic rocks, but the meaning of this association remains elusive. Understanding the association between high Sr/Y magmatic rocks and porphyry-type deposits is essential to develop genetic models that can be used for exploration purposes. Here we present results on a Pleistocene volcano of Ecuador that highlight the behaviour of copper in magmas with variable (but generally high) Sr/Y values. We provide indirect evidence for Cu partitioning into a fluid phase exsolved at depths of ~15 km from high Sr/Y (>70) andesitic magmas before sulphide saturation. This lends support to the hypothesis that large amounts of Cu- and S-bearing fluids can be accumulated into and released from a long-lived high Sr/Y deep andesitic reservoir to a shallower magmatic-hydrothermal system with the potential of generating large porphyry-type deposits.

  18. Intelligent Interfaces for Mining Large-Scale RNAi-HCS Image Databases

    PubMed Central

    Lin, Chen; Mak, Wayne; Hong, Pengyu; Sepp, Katharine; Perrimon, Norbert

    2010-01-01

    Recently, High-content screening (HCS) has been combined with RNA interference (RNAi) to become an essential image-based high-throughput method for studying genes and biological networks through RNAi-induced cellular phenotype analyses. However, a genome-wide RNAi-HCS screen typically generates tens of thousands of images, most of which remain uncategorized due to the inadequacies of existing HCS image analysis tools. Until now, it still requires highly trained scientists to browse a prohibitively large RNAi-HCS image database and produce only a handful of qualitative results regarding cellular morphological phenotypes. For this reason we have developed intelligent interfaces to facilitate the application of the HCS technology in biomedical research. Our new interfaces empower biologists with computational power not only to effectively and efficiently explore large-scale RNAi-HCS image databases, but also to apply their knowledge and experience to interactive mining of cellular phenotypes using Content-Based Image Retrieval (CBIR) with Relevance Feedback (RF) techniques. PMID:21278820

  19. Multi-day convective-environmental evolution prior to tropical cyclone formation from geostationary satellite measurements

    NASA Astrophysics Data System (ADS)

    Chang, Minhee; Ho, Chang-Hoi; Park, Myung-Sook

    2016-04-01

    Tropical cyclones (TCs) are developed through persistent latent heating taken from deep convective process. By analyzing aircraft and polar-orbit satellite observations, distinct upper-level warm-core induced by strong updraft was found in pre-TCs while vertically uniform temperature profile is found in non-developers. Precipitation is also broader and more frequent in developing disturbances than in nondeveloping ones. However, large uncertainties remain in determining which disturbance will develop into TC by using observation snap-shots. Here, five-day systematic evolution of deep convection and environments in developing (80) and non-developing (491) disturbances are examined over the western North Pacific for 20072009 by using geostationary satellite observation. Daily, positive tendencies in the hourly time series of the area of the MTSAT-1R infrared (IR) and water vapor (WV) brightness temperature difference < 0 are used to define single diurnal convective burst (CB) event. In terms of single CB properties (duration, expanded convective area, maximum convective area, and expanding rate), developing and nondeveloping disturbances shows significantly different mean values in the statistics, but it is not effective to estimate TC genesis. The presence of continuous CB events more than two days (i.e. multi-day CB; mCB), however, is generally found in developing disturbances. Based on the presence and absence mCB in the IR-WV time series, two different evolutions from Day 1 to Day 5 of TC formation (non-development) are explored, in which Day 6 is set to be a TC formation day (Day5 as non-development vortex decaying day). The majority of developing disturbances with mCB (83 %) initially have stronger large-scale vorticity with low-level maxima, tend to have gradually increasing deep convective area and vorticities at low-to-upper troposphere. By contrast, few developing disturbances (17 %) without mCB are pre-conditioned by much weaker large-scale vorticity. Due to adjacent dry air, resultant intensification was driven only after from Day 3 with rapid increase in relative vorticity and abrupt convective burst. There also exist many non-developing cases with mCB (54 %), which appear to candidates of TC formation as gradually increasing their convective area from Day 1 to Day 4. Due to the initially weak large-scale vorticity, they eventually decay on Day 5. For nondeveloping disturbances without mCB (46%), initially weak large-scale vorticity as well as dry atmosphere resulted in one-time deep convection and decay. Thus, this study suggests that the multiple days of convective burst, which initially accompanies strong low- to mid-troposphere large-scale vorticity, is important in TC formation.

  20. Removing brakes on adult brain plasticity: from molecular to behavioral interventions

    PubMed Central

    Bavelier, D.; Levi, D.M.; Li, R.W.; Dan, Y.; Hensch, T.K.

    2010-01-01

    Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as peri-neuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects. PMID:21068299

  1. Ultrahigh-pressure polyamorphism in GeO2 glass with coordination number >6

    NASA Astrophysics Data System (ADS)

    Kono, Yoshio; Kenney-Benson, Curtis; Ikuta, Daijo; Shibazaki, Yuki; Wang, Yanbin; Shen, Guoyin

    2016-03-01

    Knowledge of pressure-induced structural changes in glasses is important in various scientific fields as well as in engineering and industry. However, polyamorphism in glasses under high pressure remains poorly understood because of experimental challenges. Here we report new experimental findings of ultrahigh-pressure polyamorphism in GeO2 glass, investigated using a newly developed double-stage large-volume cell. The Ge-O coordination number (CN) is found to remain constant at ∼6 between 22.6 and 37.9 GPa. At higher pressures, CN begins to increase rapidly and reaches 7.4 at 91.7 GPa. This transformation begins when the oxygen-packing fraction in GeO2 glass is close to the maximal dense-packing state (the Kepler conjecture = ∼0.74), which provides new insights into structural changes in network-forming glasses and liquids with CN higher than 6 at ultrahigh-pressure conditions.

  2. The transition to value-based care.

    PubMed

    Ray, Jordan C; Kusumoto, Fred

    2016-10-01

    Delivery of medical care is evolving rapidly worldwide. Over the past several years in the USA, there has been a rapid shift in reimbursement from a simple fee-for-service model to more complex models that attempt to link payment to quality and value. Change in any large system can be difficult, but with medicine, the transition to a value-based system has been particularly hard to implement because both quality and cost are difficult to quantify. Professional societies and other medical groups are developing different programs in an attempt to define high value care. However, applying a national standard of value for any treatment is challenging, since value varies from person to person, and the individual benefit must remain the central tenet for delivering best patient-centered medical care. Regardless of the specific operational features of the rapidly changing healthcare environment, physicians must first and foremost always remain patient advocates.

  3. Microgravity protein crystallization

    PubMed Central

    McPherson, Alexander; DeLucas, Lawrence James

    2015-01-01

    Over the past 20 years a variety of technological advances in X-ray crystallography have shortened the time required to determine the structures of large macromolecules (i.e., proteins and nucleic acids) from several years to several weeks or days. However, one of the remaining challenges is the ability to produce diffraction-quality crystals suitable for a detailed structural analysis. Although the development of automated crystallization systems combined with protein engineering (site-directed mutagenesis to enhance protein solubility and crystallization) have improved crystallization success rates, there remain hundreds of proteins that either cannot be crystallized or yield crystals of insufficient quality to support X-ray structure determination. In an attempt to address this bottleneck, an international group of scientists has explored use of a microgravity environment to crystallize macromolecules. This paper summarizes the history of this international initiative along with a description of some of the flight hardware systems and crystallization results. PMID:28725714

  4. Rearing the Fruit Fly Drosophila melanogaster Under Axenic and Gnotobiotic Conditions.

    PubMed

    Koyle, Melinda L; Veloz, Madeline; Judd, Alec M; Wong, Adam C-N; Newell, Peter D; Douglas, Angela E; Chaston, John M

    2016-07-30

    The influence of microbes on myriad animal traits and behaviors has been increasingly recognized in recent years. The fruit fly Drosophila melanogaster is a model for understanding microbial interactions with animal hosts, facilitated by approaches to rear large sample sizes of Drosophila under microorganism-free (axenic) conditions, or with defined microbial communities (gnotobiotic). This work outlines a method for collection of Drosophila embryos, hypochlorite dechorionation and sterilization, and transfer to sterile diet. Sterilized embryos are transferred to sterile diet in 50 ml centrifuge tubes, and developing larvae and adults remain free of any exogenous microbes until the vials are opened. Alternatively, flies with a defined microbiota can be reared by inoculating sterile diet and embryos with microbial species of interest. We describe the introduction of 4 bacterial species to establish a representative gnotobiotic microbiota in Drosophila. Finally, we describe approaches for confirming bacterial community composition, including testing if axenic Drosophila remain bacteria-free into adulthood.

  5. Isotopic signals of summer denitrification in a northern hardwood forested catchment.

    PubMed

    Wexler, Sarah K; Goodale, Christine L; McGuire, Kevin J; Bailey, Scott W; Groffman, Peter M

    2014-11-18

    Despite decades of measurements, the nitrogen balance of temperate forest catchments remains poorly understood. Atmospheric nitrogen deposition often greatly exceeds streamwater nitrogen losses; the fate of the remaining nitrogen is highly uncertain. Gaseous losses of nitrogen to denitrification are especially poorly documented and are often ignored. Here, we provide isotopic evidence (δ(15)NNO3 and δ(18)ONO3) from shallow groundwater at the Hubbard Brook Experimental Forest indicating extensive denitrification during midsummer, when transient, perched patches of saturation developed in hillslopes, with poor hydrological connectivity to the stream, while streamwater showed no isotopic evidence of denitrification. During small rain events, precipitation directly contributed up to 34% of streamwater nitrate, which was otherwise produced by nitrification. Together, these measurements reveal the importance of denitrification in hydrologically disconnected patches of shallow groundwater during midsummer as largely overlooked control points for nitrogen loss from temperate forest catchments.

  6. Isotopic signals of summer denitrification in a northern hardwood forested catchment

    PubMed Central

    Wexler, Sarah K.; Goodale, Christine L.; Bailey, Scott W.; Groffman, Peter M.

    2014-01-01

    Despite decades of measurements, the nitrogen balance of temperate forest catchments remains poorly understood. Atmospheric nitrogen deposition often greatly exceeds streamwater nitrogen losses; the fate of the remaining nitrogen is highly uncertain. Gaseous losses of nitrogen to denitrification are especially poorly documented and are often ignored. Here, we provide isotopic evidence (δ15NNO3 and δ18ONO3) from shallow groundwater at the Hubbard Brook Experimental Forest indicating extensive denitrification during midsummer, when transient, perched patches of saturation developed in hillslopes, with poor hydrological connectivity to the stream, while streamwater showed no isotopic evidence of denitrification. During small rain events, precipitation directly contributed up to 34% of streamwater nitrate, which was otherwise produced by nitrification. Together, these measurements reveal the importance of denitrification in hydrologically disconnected patches of shallow groundwater during midsummer as largely overlooked control points for nitrogen loss from temperate forest catchments. PMID:25368188

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

    Cheng, Shiwang; Xie, Shi-Jie; Carrillo, Jan-Michael Y.

    Polymer nanocomposites (PNCs) are important materials that are widely used in many current technologies and potentially have broader applications in the future due to their excellent property of tunability, light weight and low cost. But, expanding the limits in property enhancement remains a fundamental scientific challenge. We demonstrate that well-dispersed, small (diameter ~1.8 nm) nanoparticles with attractive interactions lead to unexpectedly large and qualitatively new changes in PNC structural dynamics in comparison to conventional composites based on particles of diameter ~10-50 nm. At the same time, the zero-shear viscosity at high temperatures remains comparable to that of the neat polymer,more » thereby retaining good processibility and resolving a major challenge in PNC applications. These results suggest that the nanoparticle mobility and relatively short lifetimes of nanoparticlepolymer associations open qualitatively new horizons in tunability of macroscopic properties in nanocomposites with high potential for the development of new functional materials.« less

  8. Recent geologic development of Lake Michigan (U.S.A.)

    USGS Publications Warehouse

    Gross, D.L.; Cahill, R.A.

    1983-01-01

    The stresses placed on Lake Michigan since the advent of industrialization require knowledge of the sedimentology of the whole lake in order to make informed decisions for environmental planning. Sediment accumulation rates are low: areas of the lake receiving the most sediment average only 1 mm a-1; deep-water basins average 0.1 to 0.5 mm a-1; and large areas are not receiving any sediment. Sediment was deposited rapidly (typically 5 mm a-1), in the form of rock flour, during the deglaciation of both Lake Michigan and Lake Superior Basins. Then the rate of accumulation decreased by 80-90% and has remained relatively constant since final deglaciation. Because active sedimentation occurs mostly in the deep water areas of the lake, the sediment remains undisturbed and contains a record of the chemical history of the lake. ?? 1983 Dr W. Junk Publishers.

  9. Natural history of acute and chronic hepatitis C.

    PubMed

    Maasoumy, Benjamin; Wedemeyer, Heiner

    2012-08-01

    Hepatitis C virus (HCV) infection remains a major global health burden. Hepatitis C causes significant liver-related morbidity and mortality due to hepatic decompensation and development of hepatocellular carcinoma. In addition, extra-hepatic manifestations of hepatitis C are frequent. There is a very large interindividual variability in the natural history of both acute and chronic hepatitis C which can be explained in part by a combination of various host, viral and environmental factors. Successful antiviral treatment can prevent short- and long-term complications of HCV infection in many patients. Still, the relative contribution of distinct risk factors for disease progression in different phases of HCV infection needs to be better defined. Personalized treatment approaches for HCV infection should consider individual risk profiles to avoid both under- and over-treatment - which will remain important also in upcoming era of interferon-free treatment of hepatitis C. Copyright © 2012. Published by Elsevier Ltd.

  10. [Adaptive desensitization for acetylsalicylic acid hypersensitivity: A success story?].

    PubMed

    Mühlmeier, G; Hausch, R; Maier, H

    2015-10-01

    Adaptive desensitization still remains the only causative therapy for acetylsalicylic acid (ASA) hypersensitivity and is carried out nearly worldwide. To date there are hardly any data available on disease development under current desensitization therapy and longitudinal data in particular are missing. Out of a large collective of patients with proven hypersensitivity to ASA, 194 patients with initiated desensitization treatment were observed for periods up to 5 years (average 32 months). Patients with immediate reactions to systemic challenge tests revealed a response rate of 77% after 12 months of therapy. In this period 12% reached complete remission, 38% showed a clear reduction in symptoms, 32% reached partial remission, 13% remained unchanged and 5% suffered from disease progression. Adaptive desensitization therapy for hypersensitivity to ASA has been shown to be an effective causative therapy and chronic hyperplastic sinusitis as well as bronchial asthma could be improved. For the determination of maintenance dosages and required time periods more data are needed.

  11. VZV Replication Assays

    PubMed Central

    Griffiths, Samantha J.; Haas, Jürgen

    2017-01-01

    Varicella zoster virus (VZV) is a human herpesvirus which causes Varicella (chickenpox) upon primary infection and Zoster (shingles) following reactivation from latency (von Bokay, 1909). Whilst VZV is extensively studied, inherent features of VZV replication, such as cell-association of virus particles during in vitro culture and a restricted host range (limited to humans and some other primates) mean the cellular and viral mechanisms underlying VZV reactivation and pathogenesis remain largely uncharacterised. Much remains to be learnt about VZV, interactions with its host, and the development of disease. This protocol describes a basic VZV replication assay using a recombinant VZV-GFP reporter virus. As VZV is highly cell-associated in tissue culture, the reporter virus inoculum described here is a preparation of infected cells. This reporter virus-infected cell line can be used in combination with siRNA gene depletion or cDNA overexpression transfection protocols to determine the effect of individual cellular genes on virus replication. PMID:29085851

  12. Shells and Bones: A Forensic Medicine Study of the Association of Terrestrial Snail Allopeas micra with Buried Human Remains in Brazil.

    PubMed

    Galvão, Malthus Fonseca; Pujol-Luz, José Roberto; de Assis Pujol-Luz, Cristiane Vieira; de Rosa, Cássio Thyone Almeida; Simone, Luiz Ricardo L; Báo, Sônia Nair; Barros-Cordeiro, Karine Brenda; Pessoa, Larissa; Bissacot, Giovanna

    2015-09-01

    Little is known regarding the scavenger fauna associated with buried human corpses, particularly in clandestine burials. We report the presence of 20 shells of the terrestrial snail Allopeas micra, within hollow bones of human remains buried for 5 years, during the process of collecting DNA material. The fact that a large number of shells of A. micra had been found in the corpse and in the crime scene supports the assumption that there was no attempt to remove the corpse from the area where the crime occurred. Despite this, our observations cannot be used to estimate the postmortem interval because there is no precise knowledge about the development of this species. This is the first record of a terrestrial snail associated with a human corpse and its role in this forensic medicine case. © 2015 American Academy of Forensic Sciences.

  13. Gallstone Ileus: Dilemma in the Management

    PubMed Central

    Bakhshi, Girish D.; Chincholkar, Rajesh G.; Agarwal, Jasmine R.; Gupta, Madhukar R.; Gokhe, Prachiti S.; Nadkarni, Amogh R.

    2017-01-01

    Gallstone ileus is a mechanical intestinal obstruction caused due to impaction of a large gallstone within the bowel. The ideal treatment of gallstone ileus remains controversial, with the main dilemma being between a one-stage and a two-stage surgical procedure. A 69-year old male patient presented with gallstone ileus. A one-stage procedure with enterolithotomy and primary closure of duodenal fistula was done. His immediate postoperative recovery was uneventful, but after 3 weeks of surgery, he developed respiratory complications and expired of multi-organ failure. In gallstone ileus, patient presents with symptoms of intestinal obstruction. Enterolithotomy alone remains the most common operative method, but the definitive surgical management is still under research. An intraoperative dilemma between a one-stage or two-stage surgery is difficult to resolve in absence of clear guidelines. Hence, more studies are required to come to a consensus in deciding its definitive management. PMID:28808520

  14. Examination of the Reelfoot Rift Petroleum System, south-central United States, and the elements that remain for potential exploration and development

    USGS Publications Warehouse

    Coleman, James; Pratt, Thomas L.

    2016-01-01

    No production has been established in the Reel-foot rift. However, at least nine of 22 exploratory wells have reported petroleum shows, mainly gas shows with some asphalt or solid hydrocarbon residue. Regional seismic profiling shows the presence of two large inversion structures (Blytheville arch and Pascola arch). The Blytheville arch is marked by a core of structurally thickened Elvins Shale, whereas the Pascola arch reflects the structural uplift of a portion of the entire rift basin. Structural uplift and faulting within the Reelfoot rift since the late Paleozoic appear to have disrupted older conventional hydrocarbon traps and likely spilled any potential conventional petroleum accumulations. The remaining potential resources within the Reelfoot rift are likely shale gas accumulations within the Elvins Shale; however, reservoir continuity and porosity as well as pervasive faulting appear to be significant future challenges for explorers and drillers.

  15. Serving the world's poor, profitably.

    PubMed

    Prahalad, C K; Hammond, Allen

    2002-09-01

    By stimulating commerce and development at the bottom of the economic pyramid, multi-nationals could radically improve the lives of billions of people and help create a more stable, less dangerous world. Achieving this goal does not require MNCs to spearhead global social-development initiatives for charitable purposes. They need only act in their own self-interest. How? The authors lay out the business case for entering the world's poorest markets. Fully 65% of the world's population earns less than $2,000 per year--that's 4 billion people. But despite the vastness of this market, it remains largely untapped. The reluctance to invest is easy to understand, but it is, by and large, based on outdated assumptions of the developing world. While individual incomes may be low, the aggregate buying power of poor communities is actually quite large, representing a substantial market in many countries for what some might consider luxury goods like satellite television and phone services. Prices, and margins, are often much higher in poor neighborhoods than in their middle-class counterparts. And new technologies are already steadily reducing the effects of corruption, illiteracy, inadequate infrastructure, and other such barriers. Because these markets are in the earliest stages of economic development, revenue growth for multi-nationals entering them can be extremely rapid. MNCs can also lower costs, not only through low-cost labor but by transferring operating efficiencies and innovations developed to serve their existing operations. Certainly, succeeding in such markets requires MNCs to think creatively. The biggest change, though, has to come from executives: Unless business leaders confront their own preconceptions--particularly about the value of high-volume, low-margin businesses--companies are unlikely to master the challenges or reap the rewards of these developing markets.

  16. The evolution and exploitation of the fiber-optic hydrophone

    NASA Astrophysics Data System (ADS)

    Hill, David J.

    2007-07-01

    In the late 1970s one of the first applications identified for fibre-optic sensing was the fibre-optic hydrophone. It was recognised that the technology had the potential to provide a cost effective solution for large-scale arrays of highly sensitive hydrophones which could be interrogated over large distances. Consequently both the United Kingdom and United States navies funded the development of this sonar technology to the point that it is now deployed on submarines and as seabed arrays. The basic design of a fibre-optic hydrophone has changed little; comprising a coil of optical fibre wound on a compliant mandrel, interrogated using interferometric techniques. Although other approaches are being investigated, including the development of fibre-laser hydrophones, the interferometric approach remains the most efficient way to create highly multiplexed arrays of acoustic sensors. So much so, that the underlying technology is now being exploited in civil applications. Recently the exploration and production sector of the oil and gas industry has begun funding the development of fibre-optic seismic sensing using seabed mounted, very large-scale arrays of four component (three accelerometers and a hydrophone) packages based upon the original technology developed for sonar systems. This has given new impetus to the development of the sensors and the associated interrogation systems which has led to the technology being adopted for other commercial uses. These include the development of networked in-road fibre-optic Weigh-in-Motion sensors and of intruder detection systems which are able to acoustically monitor long lengths of border, on both land and at sea. After two decades, the fibre-optic hydrophone and associated technology has matured and evolved into a number of highly capable sensing solutions used by a range of industries.

  17. Development of numerical processing in children with typical and dyscalculic arithmetic skills—a longitudinal study

    PubMed Central

    Landerl, Karin

    2013-01-01

    Numerical processing has been demonstrated to be closely associated with arithmetic skills, however, our knowledge on the development of the relevant cognitive mechanisms is limited. The present longitudinal study investigated the developmental trajectories of numerical processing in 42 children with age-adequate arithmetic development and 41 children with dyscalculia over a 2-year period from beginning of Grade 2, when children were 7; 6 years old, to beginning of Grade 4. A battery of numerical processing tasks (dot enumeration, non-symbolic and symbolic comparison of one- and two-digit numbers, physical comparison, number line estimation) was given five times during the study (beginning and middle of each school year). Efficiency of numerical processing was a very good indicator of development in numerical processing while within-task effects remained largely constant and showed low long-term stability before middle of Grade 3. Children with dyscalculia showed less efficient numerical processing reflected in specifically prolonged response times. Importantly, they showed consistently larger slopes for dot enumeration in the subitizing range, an untypically large compatibility effect when processing two-digit numbers, and they were consistently less accurate in placing numbers on a number line. Thus, we were able to identify parameters that can be used in future research to characterize numerical processing in typical and dyscalculic development. These parameters can also be helpful for identification of children who struggle in their numerical development. PMID:23898310

  18. Rapid forest clearing in a Myanmar proposed national park threatens two newly discovered species of geckos (Gekkonidae: Cyrtodactylus)

    PubMed Central

    Oswald, Patrick; Thura, Myint Kyaw; LaJeunesse Connette, Katherine J.; Grindley, Mark E.; Songer, Melissa; Zug, George R.; Mulcahy, Daniel G.

    2017-01-01

    Myanmar’s recent transition from military rule towards a more democratic government has largely ended decades of political and economic isolation. Although Myanmar remains heavily forested, increased development in recent years has been accompanied by exceptionally high rates of forest loss. In this study, we document the rapid progression of deforestation in and around the proposed Lenya National Park, which includes some of the largest remaining areas of lowland evergreen rainforest in mainland Southeast Asia. The globally unique forests in this area are rich in biodiversity and remain a critical stronghold for many threatened and endangered species, including large charismatic fauna such as tiger and Asian elephant. We also conducted a rapid assessment survey of the herpetofauna of the proposed national park, which resulted in the discovery of two new species of bent-toed geckos, genus Cyrtodactylus. We describe these new species, C. lenya sp. nov. and C. payarhtanensis sp. nov., which were found in association with karst (i.e., limestone) rock formations within mature lowland wet evergreen forest. The two species were discovered less than 35 km apart and are each known from only a single locality. Because of the isolated nature of the karst formations in the proposed Lenya National Park, these geckos likely have geographical ranges restricted to the proposed protected area and are threatened by approaching deforestation. Although lowland evergreen rainforest has vanished from most of continental Southeast Asia, Myanmar can still take decisive action to preserve one of the most biodiverse places on Earth. PMID:28403189

  19. Student attitudes towards clinical teaching resources in complementary medicine: a focus group examination of Australian naturopathic medicine students.

    PubMed

    Wardle, Jonathan Lee; Sarris, Jerome

    2014-06-01

    Complementary medicine is forming an increasingly large part of health care in developed countries and is increasingly being formally taught in tertiary academic settings. An exploratory study of naturopathic student perceptions of, use of and attitudes towards teaching resources in naturopathic clinical training and education. Focus groups were conducted with current and recent students of 4-year naturopathic degree programmes in Brisbane and Sydney to ascertain how they interact with clinical teaching materials, and their perceptions and attitudes towards teaching materials in naturopathic education. Naturopathic students have a complex and critical relationship with their learning materials. Although naturopathic practice is often defined by traditional evidence, students want information that both supports and is critical of traditional naturopathic practices, and focuses heavily on evidence-based medicine. Students remain largely ambivalent about new teaching technologies and would prefer that these develop organically as an evolution from printed materials, rather than depart from dramatically and radically from these previously established materials. Findings from this study will assist publishers, librarians and academics develop clinical information sources that appropriately meet student expectations and support their learning requirements. © 2014 The authors. Health Information and Libraries Journal © 2014 Health Libraries Group.

  20. Semantic Likelihood Models for Bayesian Inference in Human-Robot Interaction

    NASA Astrophysics Data System (ADS)

    Sweet, Nicholas

    Autonomous systems, particularly unmanned aerial systems (UAS), remain limited in au- tonomous capabilities largely due to a poor understanding of their environment. Current sensors simply do not match human perceptive capabilities, impeding progress towards full autonomy. Recent work has shown the value of humans as sources of information within a human-robot team; in target applications, communicating human-generated 'soft data' to autonomous systems enables higher levels of autonomy through large, efficient information gains. This requires development of a 'human sensor model' that allows soft data fusion through Bayesian inference to update the probabilistic belief representations maintained by autonomous systems. Current human sensor models that capture linguistic inputs as semantic information are limited in their ability to generalize likelihood functions for semantic statements: they may be learned from dense data; they do not exploit the contextual information embedded within groundings; and they often limit human input to restrictive and simplistic interfaces. This work provides mechanisms to synthesize human sensor models from constraints based on easily attainable a priori knowledge, develops compression techniques to capture information-dense semantics, and investigates the problem of capturing and fusing semantic information contained within unstructured natural language. A robotic experimental testbed is also developed to validate the above contributions.

  1. Outcomes of three part-time faculty development fellowship programs.

    PubMed

    Anderson, W A; Stritter, F T; Mygdal, W K; Arndt, J E; Reid, A

    1997-03-01

    Part-time faculty development fellowship programs have trained large numbers of new physician faculty for family medicine education programs. This study reviews data from three part-time fellowship programs to determine how well the programs train new faculty and the academic success of fellowship graduates. Part-time fellowship programs at Michigan State University, the University of North Carolina, and the Faculty Development Center in Waco, Tex, sent written surveys to graduates as part of routine follow-up studies. Graduates were asked to report their current status in academic medicine, how they spend their time, measures of academic productivity, and assessments of how well their training prepared them for their current academic positions. Data were complied at each institution and sent to Michigan State University for analysis. The majority of graduates (76%) have remained in their academic positions, and half (49%) teach in medically underserved settings. Graduates report high levels of satisfaction with the training they received. Thirty-two percent of graduates have published peer-reviewed articles, and almost 50% have presented at peer-reviewed meetings. Part-time fellowship programs have been successful at training and retaining large numbers of new faculty for family medicine.

  2. Interprofessional transformation of clinical education: The first six years of the Veterans Affairs Centers of Excellence in Primary Care Education.

    PubMed

    Harada, Nancy D; Traylor, Laural; Rugen, Kathryn Wirtz; Bowen, Judith L; Smith, C Scott; Felker, Bradford; Ludke, Deborah; Tonnu-Mihara, Ivy; Ruberg, Joshua L; Adler, Jayson; Uhl, Kimberly; Gardner, Annette L; Gilman, Stuart C

    2018-02-20

    This paper describes the Centers of Excellence in Primary Care Education (CoEPCE), a seven-site collaborative project funded by the Office of Academic Affiliations (OAA) within the Veterans Health Administration of the United States Department of Veterans Affairs (VA). The CoEPCE was established to fulfill OAA's vision of large-scale transformation of the clinical learning environment within VA primary care settings. This was accomplished by funding new Centers within VA facilities to develop models of interprofessional education (IPE) to teach health professions trainees to deliver high quality interprofessional team-based primary care to Veterans. Using reports and data collected and maintained by the National Coordinating Center over the first six years of the project, we describe program inputs, the multicomponent intervention, activities undertaken to develop the intervention, and short-term outcomes. The findings have implications for lessons learned that can be considered by others seeking large-scale transformation of education within the clinical workplace and the development of interprofessional clinical learning environments. Within the VA, the CoEPCE has laid the foundation for IPE and collaborative practice, but much work remains to disseminate this work throughout the national VA system.

  3. Distinct Requirements for Vacuolar Protein Sorting 34 Downstream Effector Phosphatidylinositol 3-Phosphate 5-Kinase in Podocytes Versus Proximal Tubular Cells

    PubMed Central

    Venkatareddy, Madhusudan; Verma, Rakesh; Kalinowski, Anne; Patel, Sanjeevkumar R.; Shisheva, Assia

    2016-01-01

    The mechanisms by which the glomerular filtration barrier prevents the loss of large macromolecules and simultaneously, maintains the filter remain poorly understood. Recent studies proposed that podocytes have an active role in both the endocytosis of filtered macromolecules and the maintenance of the filtration barrier. Deletion of a key endosomal trafficking regulator, the class 3 phosphatidylinositol (PtdIns) 3-kinase vacuolar protein sorting 34 (Vps34), in podocytes results in aberrant endosomal membrane morphology and podocyte dysfunction. We recently showed that the vacuolation phenotype in cultured Vps34–deficient podocytes is caused by the absence of a substrate for the Vps34 downstream effector PtdIns 3-phosphate 5-kinase (PIKfyve), which phosphorylates Vps34-generated PtdIns(3)P to produce PtdIns (3,5)P2. PIKfyve perturbation and PtdIns(3,5)P2 reduction result in massive membrane vacuolation along the endosomal system, but the cell-specific functions of PIKfyve in vivo remain unclear. We show here that the genetic deletion of PIKfyve in endocytically active proximal tubular cells resulted in the development of large cytoplasmic vacuoles caused by arrested endocytic traffic progression at a late-endosome stage. In contrast, deletion of PIKfyve in glomerular podocytes did not significantly alter the endosomal morphology, even in age 18-month-old mice. However, on culturing, the PIKfyve-deleted podocytes developed massive cytoplasmic vacuoles. In summary, these data suggest that glomerular podocytes and proximal tubules have different requirements for PIKfyve function, likely related to distinct in vivo needs for endocytic flux. PMID:26825532

  4. A longitudinal twin and sibling study of the hopelessness theory of depression in adolescence and young adulthood.

    PubMed

    Waszczuk, M A; Coulson, A E; Gregory, A M; Eley, T C

    2016-07-01

    Maladaptive cognitive biases such as negative attributional style and hopelessness have been implicated in the development and maintenance of depression. According to the hopelessness theory of depression, hopelessness mediates the association between attributional style and depression. The aetiological processes underpinning this influential theory remain unknown. The current study investigated genetic and environmental influences on hopelessness and its concurrent and longitudinal associations with attributional style and depression across adolescence and emerging adulthood. Furthermore, given high co-morbidity between depression and anxiety, the study investigated whether these maladaptive cognitions constitute transdiagnostic cognitive content common to both internalizing symptoms. A total of 2619 twins/siblings reported attributional style (mean age 15 and 17 years), hopelessness (mean age 17 years), and depression and anxiety symptoms (mean age 17 and 20 years). Partial correlations revealed that attributional style and hopelessness were uniquely associated with depression but not anxiety symptoms. Hopelessness partially mediated the relationship between attributional style and depression. Hopelessness was moderately heritable (A = 0.37, 95% confidence interval 0.28-0.47), with remaining variance accounted for by non-shared environmental influences. Independent pathway models indicated that a set of common genetic influences largely accounted for the association between attributional style, hopelessness and depression symptoms, both concurrently and across development. The results provide novel evidence that associations between attributional style, hopelessness and depression symptoms are largely due to shared genetic liability, suggesting developmentally stable biological pathways underpinning the hopelessness theory of depression. Both attributional style and hopelessness constituted unique cognitive content in depression. The results inform molecular genetics research and cognitive treatment approaches.

  5. Large-scale Isolation of Highly Pure "Untouched" Regulatory T Cells in a GMP Environment for Adoptive Cell Therapy.

    PubMed

    Haase, Doreen; Puan, Kia Joo; Starke, Mireille; Lai, Tuck Siong; Soh, Melissa Yan Ling; Karunanithi, Iyswariya; San Luis, Boris; Poh, Tuang Yeow; Yusof, Nurhashikin; Yeap, Chun Hsien; Phang, Chew Yen; Chye, Willis Soon Yuan; Chan, Marieta; Koh, Mickey Boon Chai; Goh, Yeow Tee; Bertin-Maghit, Sebastien; Nardin, Alessandra; Ho, Liam Pock; Rotzschke, Olaf

    2015-01-01

    Adoptive cell therapy is an emerging treatment strategy for a number of serious diseases. Regulatory T (Treg) cells represent 1 cell type of particular interest for therapy of inflammatory conditions, as they are responsible for controlling unwanted immune responses. Initial clinical trials of adoptive transfer of Treg cells in patients with graft-versus-host disease were shown to be safe. However, obtaining sufficient numbers of highly pure and functional Treg cells with minimal contamination remains a challenge. We developed a novel approach to isolate "untouched" human Treg cells from healthy donors on the basis of negative selection using the surface markers CD49d and CD127. This procedure, which uses an antibody cocktail and magnetic beads for separation in an automated system (RoboSep), was scaled up and adapted to be compatible with good manufacturing practice conditions. With this setup we performed 9 Treg isolations from large-scale leukapheresis samples in a good manufacturing practice facility. These runs yielded sufficient numbers of "untouched" Treg cells for immediate use in clinical applications. The cell preparations consisted of viable highly pure FoxP3-positive Treg cells that were functional in suppressing the proliferation of effector T cells. Contamination with CD4 effector T cells was <10%. All other cell types did not exceed 2% in the final product. Remaining isolation reagents were reduced to levels that are considered safe. Treg cells isolated with this procedure will be used in a phase I clinical trial of adoptive transfer into leukemia patients developing graft-versus-host disease after stem cell transplantation.

  6. The European Market for Animal-Friendly Products in a Societal Context

    PubMed Central

    Ingenbleek, Paul T. M.; Harvey, David; Ilieski, Vlatko; Immink, Victor M.; de Roest, Kees; Schmid, Otto

    2013-01-01

    Simple Summary This article takes a future focus on the direction in which social forces develop the market for animal-friendly products in Europe. Although many stakeholders believe that the market is the most viable direction to improve farm animal welfare, economic productivity of the chain remains an issue that on a fundamental level conflicts with the objective to improve animal welfare. The European market for animal-friendly products is still largely fragmented and the differences between European countries are considerable. A more animal-friendly future that is achieved through the market will therefore need substantial policy attention from stakeholders in society. Abstract This article takes a future focus on the direction in which social forces develop the market for animal-friendly products in Europe. On the basis of qualitative data gathered in the context of the European EconWelfare project, the differences across eight European countries are studied. The findings suggest that, given international trade barriers that prevent an improvement of animal welfare through legislation, many stakeholders believe that the market is the most viable direction to improve farm animal welfare. Economic productivity of the chain remains, however, an issue that on a fundamental level conflicts with the objective to improve animal welfare. With the help of a deeper conceptual understanding of willingness to pay for animal welfare, the paper finds that the European market for animal-friendly products is still largely fragmented and that the differences between European countries are considerable. A more animal-friendly future that is achieved through the market will therefore need substantial policy attention from stakeholders in society. PMID:26479535

  7. Metal Nanomaterial Toxicity Variations Within the Vascular System

    PubMed Central

    Abukabda, Alaeddin B.; Stapleton, Phoebe A.; Nurkiewicz, Timothy R.

    2016-01-01

    Engineered nanomaterials (ENM) are anthropogenic materials with at least one dimension less than 100 nm. Their ubiquitous employment in biomedical and industrial applications in the absence of full toxicological assessments raises significant concerns over their safety on human health. This is a significant concern, especially for metal and metal oxide ENM as they may possess the greatest potential to impair human health. A large body of literature has developed that reflects adverse systemic effects associated with exposure to these materials, but an integrated mechanistic framework for how ENM exposure influences morbidity remains elusive. This may be due in large part to the tremendous diversity of existing ENM and the rate at which novel ENM are produced. In this review, the influence of specific ENM physicochemical characteristics and hemodynamic factors on cardiovascular toxicity are discussed. Additionally, the toxicity of metallic, and metal oxide ENM is presented in the context of the cardiovascular system and its discrete anatomical and functional components. Finally, future directions and understudied topics are presented. While it is clear that the nanotechnology boom has increased our interest in ENM toxicity, it is also evident that the field of cardiovascular nanotoxicology remains in its infancy and continued, expansive research is necessary in order to determine the mechanisms via which ENM exposure contributes to cardiovascular morbidity. PMID:27686080

  8. Advances in Dyslexia Genetics-New Insights Into the Role of Brain Asymmetries.

    PubMed

    Paracchini, S; Diaz, R; Stein, J

    2016-01-01

    Dyslexia is a common condition affecting up to 10% school-aged children. There is strong evidence that genetics plays an important role in dyslexia and is expected to be complex in nature. Few specific susceptibility factors have been identified so far, but their functional characterization has provided novel insights into the biology of dyslexia. In particular, they point to an unexpected role of candidate genes for dyslexia in the biology of cilia, cellular organelles required in many processes including the establishment of left-right asymmetries early in development. This observation has brought back into the spotlight the old idea of a link between dyslexia and handedness. Yet much of the genetics contributing to dyslexia remains unexplained. The lack of biological markers, clear diagnostic criteria, and homogeneous assessment strategies are just some of the factors preventing the collection of the cohorts powered enough for large-scale genetic studies. While the technology and methods to generate and handle large-scale data have reached unprecedented potential, the main challenge remains in establishing universal guidelines to collect suitable phenotype information across independent studies. These difficulties reflect the complex nature of dyslexia which is highly heterogeneous and often co-occurs with other neurodevelopmental disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Restoring Forest Landscapes: Important Lessons Learnt

    NASA Astrophysics Data System (ADS)

    Mansourian, Stephanie; Vallauri, Daniel

    2014-02-01

    Forest restoration at large scales, or landscapes, is an approach that is increasingly relevant to the practice of environmental conservation. However, implementation remains a challenge; poor monitoring and lesson learning lead to similar mistakes being repeated. The World Wildlife Fund (WWF), the global conservation organization, recently took stock of its 10 years of implementation of forest landscape restoration. A significant body of knowledge has emerged from the work of the WWF and its partners in the different countries, which can be of use to the wider conservation community, but for this to happen, lessons need to be systematically collected and disseminated in a coherent manner to the broader conservation and development communities and, importantly, to policy makers. We use this review of the WWF's experiences and compare and contrast it with other relevant and recent literature to highlight 11 important lessons for future large-scale forest restoration interventions. These lessons are presented using a stepwise approach to the restoration of forested landscapes. We identify the need for long-term commitment and funding, and a concerted and collaborative effort for successful forest landscape restoration. Our review highlights that monitoring impact within landscape-scale forest restoration remains inadequate. We conclude that forest restoration within landscapes is a challenging yet important proposition that has a real but undervalued place in environmental conservation in the twenty-first century.

  10. Vitamin D and Diabetic Complications: True or False Prophet?

    PubMed

    Alam, Uazman; Arul-Devah, Vilashini; Javed, Saad; Malik, Rayaz A

    2016-03-01

    Vitamin D deficiency is now recognized as a condition of increasing prevalence worldwide. Vitamin D has an established role in calcium and bone metabolism; however, more recently associations with vitamin D deficiency and risk of developing diabetes, diabetes complications, and cardiovascular disease have all been acknowledged. The vitamin D receptor is ubiquitously expressed, and experimental, in vitro, and in vivo studies strongly suggest a role in regulating the transcription of multiple genes beyond calcium homeostasis. These include antiproliferative, immunomodulatory, angiogenic, inhibition of the renin-angiotensin-aldosterone system, and neurotrophic factor expression. Observational studies report a strong association between vitamin D deficiency and cardiovascular and metabolic disorders; however, there remains a paucity of large long-term randomized clinical trials showing a benefit with treatment. An increasing body of literature suggests a possible pathogenetic role of vitamin D in the long-term complications of diabetes and vitamin D deficiency may also exacerbate symptoms of painful diabetic peripheral neuropathy. It remains unknown if supplementation of vitamin D to normal or non-deficient levels alters pathogenetic processes related to diabetic microvascular complications. With the high prevalence of vitamin D deficiency in patients with diabetes and putative mechanisms linking vitamin D deficiency to diabetic complications, there is a compelling argument for undertaking large well-designed randomized controlled trials of vitamin D supplementation.

  11. Tissue-engineered vascularized bone grafts: basic science and clinical relevance to trauma and reconstructive microsurgery.

    PubMed

    Johnson, Elizabeth O; Troupis, Theodore; Soucacos, Panayotis N

    2011-03-01

    Bone grafts are an important part of orthopaedic surgeon's armamentarium. Despite well-established bone-grafting techniques, large bone defects still represent a challenge. Efforts have therefore been made to develop osteoconductive, osteoinductive, and osteogenic bone-replacement systems. The long-term clinical goal in bone tissue engineering is to reconstruct bony tissue in an anatomically functional three-dimensional morphology. Current bone tissue engineering strategies take into account that bone is known for its ability to regenerate following injury, and for its intrinsic capability to re-establish a complex hierarchical structure during regeneration. Although the tissue engineering of bone for the reconstruction of small to moderate sized bone defects technically feasible, the reconstruction of large defects remains a daunting challenge. The essential steps towards optimized clinical application of tissue-engineered bone are dependent upon recent advances in the area of neovascularization of the engineered construct. Despite these recent advances, however, a gap from bench to bedside remains; this may ultimately be bridged by a closer collaboration between basic scientists and reconstructive surgeons. The aim of this review is to introduce the basic principles of tissue engineering of bone, outline the relevant bone physiology, and discuss the recent concepts for the induction of vascularization in engineered bone tissue. Copyright © 2011 Wiley-Liss, Inc.

  12. Novel deletions involving the USH2A gene in patients with Usher syndrome and retinitis pigmentosa

    PubMed Central

    García-García, Gema; Jaijo, Teresa; Aparisi, Maria J.; Larrieu, Lise; Faugère, Valérie; Blanco-Kelly, Fiona; Ayuso, Carmen; Roux, Anne-Francoise; Millán, José M.

    2014-01-01

    Purpose The aim of the present work was to identify and characterize large rearrangements involving the USH2A gene in patients with Usher syndrome and nonsyndromic retinitis pigmentosa. Methods The multiplex ligation-dependent probe amplification (MLPA) technique combined with a customized array-based comparative genomic hybridization (aCGH) analysis was applied to 40 unrelated patients previously screened for point mutations in the USH2A gene in which none or only one pathologic mutation was identified. Results We detected six large deletions involving USH2A in six out of the 40 cases studied. Three of the patients were homozygous for the deletion, and the remaining three were compound heterozygous with a previously identified USH2A point mutation. In five of these cases, the patients displayed Usher type 2, and the remaining case displayed nonsyndromic retinitis pigmentosa. The exact breakpoint junctions of the deletions found in USH2A in four of these cases were characterized. Conclusions Our study highlights the need to develop improved efficient strategies of mutation screening based upon next generation sequencing (NGS) that reduce cost, time, and complexity and allow simultaneous identification of all types of disease-causing mutations in diagnostic procedures. PMID:25352746

  13. A common brain network links development, aging, and vulnerability to disease.

    PubMed

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  14. Gender identity in disorders of sex development: review article.

    PubMed

    Yang, Jennifer H; Baskin, Laurence S; DiSandro, Michael

    2010-01-01

    Many concerns have been raised regarding the treatment and long-term outcome of infants born with complex genital anomalies. Debate among clinicians, psychologists, ethicists, and patient advocate groups regarding the optimal management of these individuals is ongoing. Although determining the most appropriate gender is a difficult task, this review will help clarify some of the issues at hand. A literature review which addresses the challenges of advising families about gender identity in infants and children with disorders of sex development. The evidence for endocrine effects on neurobiological development with regard to sexual behavior is compelling, although the existing outcome studies are largely anecdotal and somewhat contradictory. Gender assignment in infants born with a disorder of sex development remains only one of the many difficult decisions faced by both the treatment team and the family. Improved long-term follow-up of these patients will provide much needed feedback on previous and contemporary management. 2010 Elsevier Inc. All rights reserved.

  15. Gender development and the human brain.

    PubMed

    Hines, Melissa

    2011-01-01

    Convincing evidence indicates that prenatal exposure to the gonadal hormone, testosterone, influences the development of children's sex-typical toy and activity interests. In addition, growing evidence shows that testosterone exposure contributes similarly to the development of other human behaviors that show sex differences, including sexual orientation, core gender identity, and some, though not all, sex-related cognitive and personality characteristics. In addition to these prenatal hormonal influences, early infancy and puberty may provide additional critical periods when hormones influence human neurobehavioral organization. Sex-linked genes could also contribute to human gender development, and most sex-related characteristics are influenced by socialization and other aspects of postnatal experience, as well. Neural mechanisms underlying the influences of gonadal hormones on human behavior are beginning to be identified. Although the neural mechanisms underlying experiential influences remain largely uninvestigated, they could involve the same neural circuitry as that affected by hormones.

  16. Growth and splitting of neural sequences in songbird vocal development

    PubMed Central

    Okubo, Tatsuo S.; Mackevicius, Emily L.; Payne, Hannah L.; Lynch, Galen F.; Fee, Michale S.

    2015-01-01

    Neural sequences are a fundamental feature of brain dynamics underlying diverse behaviors, but the mechanisms by which they develop during learning remain unknown. Songbirds learn vocalizations composed of syllables; in adult birds, each syllable is produced by a different sequence of action potential bursts in the premotor cortical area HVC. Here we carried out recordings of large populations of HVC neurons in singing juvenile birds throughout learning to examine the emergence of neural sequences. Early in vocal development, HVC neurons begin producing rhythmic bursts, temporally locked to a ‘prototype’ syllable. Different neurons are active at different latencies relative to syllable onset to form a continuous sequence. Through development, as new syllables emerge from the prototype syllable, initially highly overlapping burst sequences become increasingly distinct. We propose a mechanistic model in which multiple neural sequences can emerge from the growth and splitting of a common precursor sequence. PMID:26618871

  17. High Temperature Joining and Characterization of Joint Properties in Silicon Carbide-Based Composite Materials

    NASA Technical Reports Server (NTRS)

    Halbig, Michael C.; Singh, Mrityunjay

    2015-01-01

    Advanced silicon carbide-based ceramics and composites are being developed for a wide variety of high temperature extreme environment applications. Robust high temperature joining and integration technologies are enabling for the fabrication and manufacturing of large and complex shaped components. The development of a new joining approach called SET (Single-step Elevated Temperature) joining will be described along with the overview of previously developed joining approaches including high temperature brazing, ARCJoinT (Affordable, Robust Ceramic Joining Technology), diffusion bonding, and REABOND (Refractory Eutectic Assisted Bonding). Unlike other approaches, SET joining does not have any lower temperature phases and will therefore have a use temperature above 1315C. Optimization of the composition for full conversion to silicon carbide will be discussed. The goal is to find a composition with no remaining carbon or free silicon. Green tape interlayers were developed for joining. Microstructural analysis and preliminary mechanical tests of the joints will be presented.

  18. Necessary conditions for the globalization of traditional Chinese medicine.

    PubMed

    Yu, Bei-Bei; Gong, Xiu-Lin

    2011-03-01

    With the current trend of globalization, unprecedented opportunities and enormous changes have emerged for the global development of traditional Chinese medicine (TCM). However, many old and new challenges and problems still remain, including partial or limited comprehension of acupuncture, oriental medicine and TCM, the existence of non-standardized institutes of TCM and acupuncture training schools, unqualified TCM practitioners, and problems concerning Chinese herbal medicine and inexperience in conducting TCM business. These problems will doubtlessly impede the further development of TCM worldwide in the foreseeable future. It is also clear that the globalization of TCM will require a large scale systematic project and constitute an arduous historical task. This paper aims to consolidate 6 strategic development modes to reinforce and facilitate the process of TCM globalization through a detailed analysis of both the present status and existing problems concerning the development of TCM in the United States.

  19. The international phosphate resource data base; development and maintenance

    USGS Publications Warehouse

    Bridges, Nancy J.

    1983-01-01

    The IPRDB (International Phosphate Resource Data Base) was developed to provide a single computerized source of geologic information about phosphate deposits worldwide. It is expected that this data base will encourage more thorough scientific analyses of phosphate deposits and assessments of undiscovered phosphate resources, and that methods of data collection and storage will be streamlined. Because the database was intended to serve as a repository for diverse and detailed data, a large amount of the early research effort was devoted to the design and development of the system. To date (1982), the file remains incomplete. All development work and file maintenance work on IPRDB was suspended as of October 1, 1982; this paper is intended to document the steps taken up to that date. The computer programs listed in the appendices were written specifically for the IPRDB phosbib file and are of limited future use.

  20. The design of low cost structures for extensive ground arrays

    NASA Technical Reports Server (NTRS)

    Franklin, H. A.; Leonard, R. S.

    1980-01-01

    The development of conceptual designs of solar array support structures and their foundations including considerations of the use of concrete, steel, aluminum, or timber are reported. Some cost trends were examined by varying selected parameters to determine optimum configurations. Detailed civil/structural design criteria were developed. Using these criteria, eight detailed designs for support structures and foundations were developed and cost estimates were made. As a result of the study wind was identified as the major loading experienced by these low height structures, whose arrays are likely to extend over large tracts of land. Proper wind load estimating is considered essential to developing realistic structural designs and achieving minimum cost support structures. Wind tunnel testing of a conceptual array field was undertaken and some of the resulting wind design criteria are presented. The SPS rectenna system designs may be less sensitive to wind load estimates, but consistent design criteria remain important.

  1. Ethical issues in funding research and development of drugs for neglected tropical diseases.

    PubMed

    Oprea, L; Braunack-Mayer, A; Gericke, C A

    2009-05-01

    Neglected and tropical diseases, pervasive in developing countries, are important contributors to global health inequalities. They remain largely untreated due to lack of effective and affordable treatments. Resource-poor countries cannot afford to develop the public health interventions needed to control neglected diseases. In addition, neglected diseases do not represent an attractive market for pharmaceutical industry. Although a number of international commitments, stated in the Millennium Development Goals, have been made to avert the risk of communicable diseases, tropical diseases still remain neglected due to delays in international assistance. This delay can be explained by the form international cooperation has generally taken, which is limited to promoting countries' national interests, rather than social justice at a global level. This restricts the international responsibility for global inequalities in health to a humanitarian assistance. We propose an alternative view, arguing that expanding the scope of international cooperation by promoting shared health and economic value at a global level will create new opportunities for innovative, effective and affordable interventions worldwide. It will also promote neglected diseases as a global research priority. We build our argument on a proposal to replace the patenting system that currently regulates pharmaceutical research with a global fund to reward this research based on actual decreases in morbidity and mortality at a global level. We argue that this approach is beneficent because it will decrease global health inequalities and promote social justice worldwide.

  2. Eccrine sweat gland development and sweat secretion

    PubMed Central

    Cui, Chang-Yi; Schlessinger, David

    2017-01-01

    Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell-specific Foxa1 expression was shown to regulate a Ca2+-dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers – for example InsP3 and Ca2+ – and downstream ion channels/transporters in the framework of a Na+-K+-Cl− cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid–base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined. PMID:26014472

  3. Candida vaccines development from point view of US patent application.

    PubMed

    Wang, Shyh-Jen

    2011-11-01

    Candidiasis is the fourth most common bloodstream infection in hospitalized patients in the United States. Moreover, the mortality rate from Candida infections remains high, even after treatment with antifungal therapy. Vaccination would be a promising strategy for prevention of invasive fungal infections. In order to examine the main trends in anticandidal vaccine patenting activity, we conducted an analysis for anticandidal vaccine patents. We find 190 issued patent and 940 patent application documents containing the keywords Candida and vaccine within claims in the USA. Candida vaccines development, as evidenced by the numbers of issued patents, has decreased since the year 2002. Furthermore, the number of patent applications in Candida vaccines may indicate the strength of engaged resources were also in the status of stagnation during 2005-2007 and even a decline in 2008. Academic and nonprofit research institutions not only account for a large share of Candida vaccines patents but also apply for patents continually. Based on this analysis, the strength of Candida vaccines resources seems to remain stagnant in recent years due to patent prosecution or technical barrier in the filed of Candida vaccines. Therefore, we consider that Candida vaccines technology to still be under development and the researchers are still looking for scientific breakthrough in the filed.

  4. The process, logistics and challenges of implementing clinical supervision in a generalist tertiary referral hospital.

    PubMed

    Brunero, Scott; Lamont, Scott

    2012-03-01

    Clinical supervision (CS) has been identified within nursing as a process for improving clinical practice and reducing the emotional burden of nursing practice. Little is known about its implementation across large tertiary referral hospitals. The purpose of this study is to evaluate the implementation of clinical supervision across several different nursing specialities at a teaching hospital in Sydney, Australia. Using a model of nursing implementation science, a process was developed at the study site that facilitated the development, implementation and evaluation of the project. After a 6-month study period, the CS groups were postevaluated using a survey tool developed for the project. A total of nine CS groups were in operation over the 6-month study period. A predominant focus within the sessions was one of the collegial support and developing standards of practice. The process was able to achieve wide hospital-based support for the role of CS from the senior nurse executives to junior nurses. Whilst there was overall positive support for the CS groups, logistical and resource challenges remain, in the effective roll out of CS to large numbers of nurses. © 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.

  5. New concepts in anaerobic digestion processes: recent advances and biological aspects.

    PubMed

    Castellano-Hinojosa, Antonio; Armato, Caterina; Pozo, Clementina; González-Martínez, Alejandro; González-López, Jesús

    2018-06-01

    Waste treatment and the simultaneous production of energy have gained great interest in the world. In the last decades, scientific efforts have focused largely on improving and developing sustainable bioprocess solutions for energy recovery from challenging waste. Anaerobic digestion (AD) has been developed as a low-cost organic waste treatment technology with a simple setup and relatively limited investment and operating costs. Different technologies such as one-stage and two-stage AD have been developed. The viability and performance of these technologies have been extensively reported, showing the supremacy of two-stage AD in terms of overall energy recovery from biomass under different substrates, temperatures, and pH conditions. However, a comprehensive review of the advantages and disadvantages of these technologies is still lacking. Since microbial ecology is critical to developing successful AD, many studies have shown the structure and dynamics of archaeal and bacterial communities in this type of system. However, the role of Eukarya groups remains largely unknown to date. In this review, we provide a comprehensive review of the role, abundance, dynamics, and structure of archaeal, bacterial, and eukaryal communities during the AD process. The information provided could help researchers to select the adequate operational parameters to obtain the best performance and biogas production results.

  6. Wide-Open: Accelerating public data release by automating detection of overdue datasets

    PubMed Central

    Poon, Hoifung; Howe, Bill

    2017-01-01

    Open data is a vital pillar of open science and a key enabler for reproducibility, data reuse, and novel discoveries. Enforcement of open-data policies, however, largely relies on manual efforts, which invariably lag behind the increasingly automated generation of biological data. To address this problem, we developed a general approach to automatically identify datasets overdue for public release by applying text mining to identify dataset references in published articles and parse query results from repositories to determine if the datasets remain private. We demonstrate the effectiveness of this approach on 2 popular National Center for Biotechnology Information (NCBI) repositories: Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA). Our Wide-Open system identified a large number of overdue datasets, which spurred administrators to respond directly by releasing 400 datasets in one week. PMID:28594819

  7. Wide-Open: Accelerating public data release by automating detection of overdue datasets.

    PubMed

    Grechkin, Maxim; Poon, Hoifung; Howe, Bill

    2017-06-01

    Open data is a vital pillar of open science and a key enabler for reproducibility, data reuse, and novel discoveries. Enforcement of open-data policies, however, largely relies on manual efforts, which invariably lag behind the increasingly automated generation of biological data. To address this problem, we developed a general approach to automatically identify datasets overdue for public release by applying text mining to identify dataset references in published articles and parse query results from repositories to determine if the datasets remain private. We demonstrate the effectiveness of this approach on 2 popular National Center for Biotechnology Information (NCBI) repositories: Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA). Our Wide-Open system identified a large number of overdue datasets, which spurred administrators to respond directly by releasing 400 datasets in one week.

  8. Quantifying the uncertainty in heritability.

    PubMed

    Furlotte, Nicholas A; Heckerman, David; Lippert, Christoph

    2014-05-01

    The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach, in which heritability is estimated using maximum likelihood and its variance is quantified through an asymptotic normal approximation. An alternative approach is to quantify the uncertainty in heritability through its Bayesian posterior distribution. In this paper, we develop the latter approach, make it computationally efficient and compare it to the frequentist approach. We show theoretically that, for a sufficiently large sample size and intermediate values of heritability, the two approaches provide similar results. Using the Atherosclerosis Risk in Communities cohort, we show empirically that the two approaches can give different results and that the variance/uncertainty can remain large.

  9. Early-branching Gut Fungi Possess A Large, And Comprehensive Array Of Biomass-Degrading Enzymes

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

    Solomon, Kevin V.; Haitjema, Charles; Henske, John K.

    The fungal kingdom is the source of almost all industrial enzymes in use for lignocellulose bioprocessing. Its more primitive members, however, remain relatively unexploited. We developed a systems-level approach that integrates RNA-Seq, proteomics, phenotype and biochemical studies of relatively unexplored early-branching free-living fungi. Anaerobic gut fungi isolated from herbivores produce a large array of biomass-degrading enzymes that synergistically degrade crude, unpretreated plant biomass, and are competitive with optimized commercial preparations from Aspergillus and Trichoderma. Compared to these model platforms, gut fungal enzymes are unbiased in substrate preference due to a wealth of xylan-degrading enzymes. These enzymes are universally catabolite repressed,more » and are further regulated by a rich landscape of noncoding regulatory RNAs. Furthermore, we identified several promising sequence divergent enzyme candidates for lignocellulosic bioprocessing.« less

  10. Lightweight and Statistical Techniques for Petascale Debugging: Correctness on Petascale Systems (CoPS) Preliminry Report

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

    de Supinski, B R; Miller, B P; Liblit, B

    2011-09-13

    Petascale platforms with O(10{sup 5}) and O(10{sup 6}) processing cores are driving advancements in a wide range of scientific disciplines. These large systems create unprecedented application development challenges. Scalable correctness tools are critical to shorten the time-to-solution on these systems. Currently, many DOE application developers use primitive manual debugging based on printf or traditional debuggers such as TotalView or DDT. This paradigm breaks down beyond a few thousand cores, yet bugs often arise above that scale. Programmers must reproduce problems in smaller runs to analyze them with traditional tools, or else perform repeated runs at scale using only primitive techniques.more » Even when traditional tools run at scale, the approach wastes substantial effort and computation cycles. Continued scientific progress demands new paradigms for debugging large-scale applications. The Correctness on Petascale Systems (CoPS) project is developing a revolutionary debugging scheme that will reduce the debugging problem to a scale that human developers can comprehend. The scheme can provide precise diagnoses of the root causes of failure, including suggestions of the location and the type of errors down to the level of code regions or even a single execution point. Our fundamentally new strategy combines and expands three relatively new complementary debugging approaches. The Stack Trace Analysis Tool (STAT), a 2011 R&D 100 Award Winner, identifies behavior equivalence classes in MPI jobs and highlights behavior when elements of the class demonstrate divergent behavior, often the first indicator of an error. The Cooperative Bug Isolation (CBI) project has developed statistical techniques for isolating programming errors in widely deployed code that we will adapt to large-scale parallel applications. Finally, we are developing a new approach to parallelizing expensive correctness analyses, such as analysis of memory usage in the Memgrind tool. In the first two years of the project, we have successfully extended STAT to determine the relative progress of different MPI processes. We have shown that the STAT, which is now included in the debugging tools distributed by Cray with their large-scale systems, substantially reduces the scale at which traditional debugging techniques are applied. We have extended CBI to large-scale systems and developed new compiler based analyses that reduce its instrumentation overhead. Our results demonstrate that CBI can identify the source of errors in large-scale applications. Finally, we have developed MPIecho, a new technique that will reduce the time required to perform key correctness analyses, such as the detection of writes to unallocated memory. Overall, our research results are the foundations for new debugging paradigms that will improve application scientist productivity by reducing the time to determine which package or module contains the root cause of a problem that arises at all scales of our high end systems. While we have made substantial progress in the first two years of CoPS research, significant work remains. While STAT provides scalable debugging assistance for incorrect application runs, we could apply its techniques to assertions in order to observe deviations from expected behavior. Further, we must continue to refine STAT's techniques to represent behavioral equivalence classes efficiently as we expect systems with millions of threads in the next year. We are exploring new CBI techniques that can assess the likelihood that execution deviations from past behavior are the source of erroneous execution. Finally, we must develop usable correctness analyses that apply the MPIecho parallelization strategy in order to locate coding errors. We expect to make substantial progress on these directions in the next year but anticipate that significant work will remain to provide usable, scalable debugging paradigms.« less

  11. A Preliminary Assessment of the Cultural Resources within the Millican Project, Navasota River Basin, Brazos, Grimes, Leon, Madison and Robertson Counties, Texas. Reports of Investigations, Number 19.

    DTIC Science & Technology

    1982-02-01

    suggests their use as cooking vessels. An analysis of the faunal remains indicates that deer was the primary large namal exploited; turtle remains are...identified include deer (64.4%), turtle (14.3%), jackrabbit (14.3%) and an unidentified large bird (7%). The Paleoindian materials recovered from the...prehistoric archeologi- cal sites within this area and the cultural adaptations which they rep- resent are neither too limited in nature nor too nebulous to be

  12. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

    PubMed

    Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

    2016-02-01

    Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided.

  13. Recent progress in multi-electrode spike sorting methods

    PubMed Central

    Lefebvre, Baptiste; Yger, Pierre; Marre, Olivier

    2017-01-01

    In recent years, arrays of extracellular electrodes have been developed and manufactured to record simultaneously from hundreds of electrodes packed with a high density. These recordings should allow neuroscientists to reconstruct the individual activity of the neurons spiking in the vicinity of these electrodes, with the help of signal processing algorithms. Algorithms need to solve a source separation problem, also known as spike sorting. However, these new devices challenge the classical way to do spike sorting. Here we review different methods that have been developed to sort spikes from these large-scale recordings. We describe the common properties of these algorithms, as well as their main differences. Finally, we outline the issues that remain to be solved by future spike sorting algorithms. PMID:28263793

  14. 'Racial differences have to be considered': Lauretta Bender, Bellevue Hospital, and the African American psyche, 1936-52.

    PubMed

    Doyle, Dennis

    2010-06-01

    This paper examines one US psychiatrist's engagement between 1936 and 1952 with a racialist strain of evolutionary thought. When Lauretta Bender began working with Bellevue Hospital's disproportionately black population, the psychiatric literature still circulated the crude evolutionary proposition that blacks remained stuck at a more primitive stage of development. In the 1930s, drawing insights from holistic, mechanistic and environmentalist thinking on the relationship between mind and body, Bender developed her own more circumspect racialist position. Although she largely abandoned her underdetermined version of racialism in the 1940s for an approach that left out race as an active factor of analysis, this paper contends that she probably never wrote off black primitivity as a theoretical possibility.

  15. High-Throughput Assay Optimization and Statistical Interpolation of Rubella-Specific Neutralizing Antibody Titers

    PubMed Central

    Lambert, Nathaniel D.; Pankratz, V. Shane; Larrabee, Beth R.; Ogee-Nwankwo, Adaeze; Chen, Min-hsin; Icenogle, Joseph P.

    2014-01-01

    Rubella remains a social and economic burden due to the high incidence of congenital rubella syndrome (CRS) in some countries. For this reason, an accurate and efficient high-throughput measure of antibody response to vaccination is an important tool. In order to measure rubella-specific neutralizing antibodies in a large cohort of vaccinated individuals, a high-throughput immunocolorimetric system was developed. Statistical interpolation models were applied to the resulting titers to refine quantitative estimates of neutralizing antibody titers relative to the assayed neutralizing antibody dilutions. This assay, including the statistical methods developed, can be used to assess the neutralizing humoral immune response to rubella virus and may be adaptable for assessing the response to other viral vaccines and infectious agents. PMID:24391140

  16. Advanced seasonal reproductive development in a male urban bird is reflected in earlier plasma luteinizing hormone rise but not energetic status.

    PubMed

    Davies, Scott; Behbahaninia, Hirbod; Giraudeau, Mathieu; Meddle, Simone L; Waites, Kyle; Deviche, Pierre

    2015-12-01

    Urban animals inhabit an environment considerably different than do their non-urban conspecifics, and to persist urban animals must adjust to these novel environments. The timing of seasonal reproductive development (i.e., growth of gonads and secondary sex organs) is a fundamental determinant of the breeding period and is frequently advanced in urban bird populations. However, the underlying mechanism(s) by which birds adjust the timing of reproductive development to urban areas remain(s) largely unknown. Here, we compared the timing of vernal reproductive development in free-ranging urban and non-urban male Abert's Towhees, Melozone aberti, in Phoenix, Arizona, USA, and tested the non-mutually exclusive hypotheses that earlier reproductive development is due to improved energetic status and/or earlier increase in endocrine activity of the reproductive system. We found that urban birds initiated testicular development earlier than non-urban birds, but this disparity was not associated with differences in body condition, fat stores, or innate immune performance. These results provide no support for the hypothesis that energetic constraints are responsible for delayed reproductive development of non-urban relative to urban male Abert's Towhees. Urban birds did, however, increase their plasma luteinizing hormone, but not plasma testosterone, earlier than non-urban birds. These findings suggest that adjustment to urban areas by Abert's Towhees involves increases in the endocrine activity of the anterior pituitary gland and/or hypothalamus earlier than non-urban towhees. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Distinct development of the cerebral cortex in platypus and echidna.

    PubMed

    Ashwell, Ken W S; Hardman, Craig D

    2012-01-01

    Both lineages of the modern monotremes have distinctive features in the cerebral cortex, but the developmental mechanisms that produce such different adult cortical architecture remain unknown. Similarly, nothing is known about the differences and/or similarities between monotreme and therian cortical development. We have used material from the Hill embryological collection to try to answer key questions concerning cortical development in monotremes. Our findings indicate that gyrencephaly begins to emerge in the echidna brain shortly before birth (crown-rump length 12.5 mm), whereas the cortex of the platypus remains lissencephalic throughout development. The cortices of both monotremes are very immature at the time of hatching, much like that seen in marsupials, and both have a subventricular zone (SubV) within both the striatum and pallium during post-hatching development. It is particularly striking that in the platypus, this region has an extension from the palliostriatal angle beneath the developing trigeminoreceptive part of the somatosensory cortex of the lateral cortex. The putative SubV beneath the trigeminal part of S1 appears to accommodate at least two distinct types of cell and many mitotic figures and (particularly in the platypus) appears to be traversed by large numbers of thalamocortical axons as these grow in. The association with putative thalamocortical fibres suggests that this region may also serve functions similar to the subplate zone of Eutheria. These findings suggest that cortical development in each monotreme follows distinct paths from at least the time of birth, consistent with a long period of independent and divergent cortical evolution. Copyright © 2011 S. Karger AG, Basel.

  18. Why Japanese workers remain in the labor force so long: lessons for the United States?

    PubMed

    Williamson, John B; Higo, Masa

    2009-12-01

    As part of the search for ways to increase labor force participation rates among older workers in the United States, it makes sense to take a close look at evidence from Japan, one of the few industrial countries with a substantially higher labor force participation rate among older workers, particularly men, than the United States. Based mainly on prior studies and original interview data, we first discuss five potential factors which help explain why Japanese workers remain in the labor force as long as they do: (1) perceived economic necessity; (2) the large fraction of workers who are self-employed; (3) a culture that puts a high value on remaining in the labor force throughout the life course; (4) the long healthy life expectancy; and (5) the government's role in facilitating the labor force participation of older workers. We suggest that the Japanese national cultural value on remaining economically productive well into old age clearly underlies the development of the government's legislative initiatives aiming to extend the working lives of older workers. We then outline three policy suggestions for those seeking to increase labor force participation rates among older U.S. workers: (1) increase the financial incentive to workers who remain in the labor force; (2) improve public programs designed to foster efforts by older workers to become self-employed; and (3) increase the extent of government efforts to link older workers to prospective employers.

  19. Asymptomatic significant bacteriuria in the non-pregnant woman. II. Response to treatment and follow-up.

    PubMed

    Asscher, A W; Sussman, M; Waters, W E; Evans, J A; Campbell, H; Evans, K T; Williams, J E

    1969-03-29

    Short courses of nitrofurantoin and ampicillin produced an immediate cure in 80% of adult non-pregnant bacteriuric women. Of the subjects so treated, 55% remained cured at the end of one year. Over the same follow-up period 36% of untreated bacteriuric women developed a spontaneous remission of bacteriuria. Treatment failed to prevent the development of symptomatic infection, and the reinfections which followed successful treatment were more commonly associated with the development of symptoms than the persistent or relapsing infections in untreated or unsuccessfully treated subjects.It is concluded that a search for bacteriuria in non-pregnant women is unlikely to be of value as a preventive measure, since in many instances it fails to detect urinary tract infection at an early stage and since treatment by methods suitable for large-scale use is ineffective.

  20. Insect succession on remains of human and animals in Shenzhen, China.

    PubMed

    Wang, Yu; Ma, Meng-Yun; Jiang, Xin-Yu; Wang, Jiang-Feng; Li, Liang-Liang; Yin, Xiao-Jun; Wang, Min; Lai, Yue; Tao, Lu-Yang

    2017-02-01

    Most forensic entomological succession studies have been carried out using pig or rabbit carcasses; however, there have been few studies on the differences between insect succession patterns on human cadavers and on animal carcasses. In order to clarify the differences between decomposition and insect succession patterns of human cadavers and animal carcasses, one 49.5kg human cadaver, two large pig carcasses (45 and 48kg), two small pig carcasses (23 and 25kg) and two rabbit carcasses (both 1.75kg) were placed in the same field conditions in Shenzhen, China for a comparative study on August, 2013. The results indicated that: (1) The duration from fresh to skeletonization is in order of human cadaver>large pig carcasses>small pig carcasses>rabbit carcasses; (2) insect assemblages (including developmental stages) are more complex on larger carcasses, in order of human cadaver=large pig carcasses>small pig carcasses>rabbit carcasses; (3) the developmental rates of the same forensically important fly species on all carcasses are consistent; (4) all identified species of Calliphoridae can complete development of one generation on human cadaver, and both large and small pig carcasses, while on rabbit carcasses, only a subset of the Calliphoridae species can finish development of one generation; (5) beetles can generate offspring on human cadaver, and both large and small pig carcasses, while they do not generate offspring on rabbit carcasses. This study provides useful comparative data for decomposition and insect succession pattern of human cadaver with animal carcasses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Advances in Multi-Sensor Scanning and Visualization of Complex Plants: the Utmost Case of a Reactor Building

    NASA Astrophysics Data System (ADS)

    Hullo, J.-F.; Thibault, G.; Boucheny, C.

    2015-02-01

    In a context of increased maintenance operations and workers generational renewal, a nuclear owner and operator like Electricité de France (EDF) is interested in the scaling up of tools and methods of "as-built virtual reality" for larger buildings and wider audiences. However, acquisition and sharing of as-built data on a large scale (large and complex multi-floored buildings) challenge current scientific and technical capacities. In this paper, we first present a state of the art of scanning tools and methods for industrial plants with very complex architecture. Then, we introduce the inner characteristics of the multi-sensor scanning and visualization of the interior of the most complex building of a power plant: a nuclear reactor building. We introduce several developments that made possible a first complete survey of such a large building, from acquisition, processing and fusion of multiple data sources (3D laser scans, total-station survey, RGB panoramic, 2D floor plans, 3D CAD as-built models). In addition, we present the concepts of a smart application developed for the painless exploration of the whole dataset. The goal of this application is to help professionals, unfamiliar with the manipulation of such datasets, to take into account spatial constraints induced by the building complexity while preparing maintenance operations. Finally, we discuss the main feedbacks of this large experiment, the remaining issues for the generalization of such large scale surveys and the future technical and scientific challenges in the field of industrial "virtual reality".

  2. High Risk of Seizures and Epilepsy after Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke

    PubMed Central

    Brondani, Rosane; Garcia de Almeida, Andrea; Abrahim Cherubini, Pedro; Mandelli Mota, Suelen; de Alencastro, Luiz Carlos; Antunes, Apio Cláudio Martins; Bianchin Muxfeldt, Marino

    2017-01-01

    Background Decompressive hemicraniectomy (DHC) is a life-saving procedure for treatment of large malignant middle cerebral artery (MCA) strokes. Post-stroke epilepsy is an additional burden for these patients, but its incidence and the risk factors for its development have been poorly investigated. Objective To report the prevalence and risk factors for post-stroke seizures and post-stroke epilepsy after DHC for treatment of large malignant MCA strokes in a cohort of 36 patients. Methods In a retrospective cohort study of 36 patients we report the timing and incidence of post-stroke epilepsy. We analyzed if age, sex, vascular risk factors, side of ischemia, reperfusion therapy, stroke etiology, extension of stroke, hemorrhagic transformation, ECASS scores, National Institutes of Health Stroke Scale (NIHSS) scores, or modified Rankin scores were risk factors for seizure or epilepsy after DHC for treatment of large MCA strokes. Results The mean patient follow-up time was 1,086 days (SD = 1,172). Out of 36 patients, 9 (25.0%) died before being discharged. After 1 year, a total of 11 patients (30.6%) had died, but 22 (61.1%) of them had a modified Rankin score ≤4. Thirteen patients (36.1%) developed seizures within the first week after stroke. Seizures occurred in 22 (61.1%) of 36 patients (95% CI = 45.17–77.03%). Out of 34 patients who survived the acute period, 19 (55.9%) developed epilepsy after MCA infarcts and DHC (95% CI = 39.21–72.59%). In this study, no significant differences were observed between the patients who developed seizures or epilepsy and those who remained free of seizures or epilepsy regarding age, sex, side of stroke, presence of the clinical risk factors studied, hemorrhagic transformation, time of craniectomy, and Rankin score after 1 year of stroke. Conclusion The incidence of seizures and epilepsy after malignant MCA infarcts submitted to DHC might be very high. Seizure might occur precociously in patients who are not submitted to anticonvulsant prophylaxis. The large stroke volume and the large cortical ischemic area seem to be the main risk factors for seizure or epilepsy development in this subtype of stroke. PMID:28359069

  3. Development of thalamocortical connectivity during infancy and its cognitive correlations.

    PubMed

    Alcauter, Sarael; Lin, Weili; Smith, J Keith; Short, Sarah J; Goldman, Barbara D; Reznick, J Steven; Gilmore, John H; Gao, Wei

    2014-07-02

    Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy. Copyright © 2014 the authors 0270-6474/14/349067-09$15.00/0.

  4. Identification of a rhythmic firing pattern in the enteric nervous system that generates rhythmic electrical activity in smooth muscle.

    PubMed

    Spencer, Nick J; Hibberd, Timothy J; Travis, Lee; Wiklendt, Lukasz; Costa, Marcello; Hu, Hongzhen; Brookes, Simon J; Wattchow, David A; Dinning, Phil G; Keating, Damien J; Sorensen, Julian

    2018-05-28

    The enteric nervous system (ENS) contains millions of neurons essential for organization of motor behaviour of the intestine. It is well established the large intestine requires ENS activity to drive propulsive motor behaviours. However, the firing pattern of the ENS underlying propagating neurogenic contractions of the large intestine remains unknown. To identify this, we used high resolution neuronal imaging with electrophysiology from neighbouring smooth muscle. Myoelectric activity underlying propagating neurogenic contractions along murine large intestine (referred to as colonic migrating motor complexes, CMMCs) consisted of prolonged bursts of rhythmic depolarizations at a frequency of ∼2 Hz. Temporal coordination of this activity in the smooth muscle over large spatial fields (∼7mm, longitudinally) was dependent on the ENS. During quiescent periods between neurogenic contractions, recordings from large populations of enteric neurons, in mice of either sex, revealed ongoing activity. The onset of neurogenic contractions was characterized by the emergence of temporally synchronized activity across large populations of excitatory and inhibitory neurons. This neuronal firing pattern was rhythmic and temporally synchronized across large numbers of ganglia at ∼2 Hz. ENS activation preceded smooth muscle depolarization, indicating rhythmic depolarizations in smooth muscle were controlled by firing of enteric neurons. The cyclical emergence of temporally coordinated firing of large populations of enteric neurons represents a unique neural motor pattern outside the central nervous system. This is the first direct observation of rhythmic firing in the ENS underlying rhythmic electrical depolarizations in smooth muscle. The pattern of neuronal activity we identified underlies the generation of CMMCs. SIGNIFICANCE STATEMENT How the enteric nervous system (ENS) generates neurogenic contractions of smooth muscle in the gastrointestinal (GI) tract has been a long-standing mystery in vertebrates. It is well known that myogenic pacemaker cells exist in the GI-tract (called Interstitial cells of Cajal, ICC) that generate rhythmic myogenic contractions. However, the mechanisms underlying the generation of rhythmic neurogenic contractions of smooth muscle in the GI-tract remains unknown. We developed a high resolution neuronal imaging method with electrophysiology to address this issue. This technique revealed a novel pattern of rhythmic coordinated neuronal firing in the ENS that has never been identified. Rhythmic neuronal firing in the ENS was found to generate rhythmic neurogenic depolarizations in smooth muscle that underlie contraction of the GI-tract. Copyright © 2018 the authors.

  5. Vancouver AIDS conference: special report. A verdict on the conference: sadly, not one world or one hope.

    PubMed

    Whiteside, A

    1996-01-01

    Although the theme of the 11th International Conference on AIDS held in Vancouver during July 7-12, 1996, was "One World, One Hope," developed and developing countries have HIV/AIDS epidemics of different magnitudes, different levels of resources with which to combat the problems, and dissimilar objectives. The latest data released at the conference report an estimated 21.8 million people to be currently living with HIV/AIDS, the vast majority of whom live in developing countries. 84% of the estimated 7.7 million AIDS cases which have occurred since the beginning of the pandemic were in Africa or Asia; only 9% were in Europe and the US. The greatest burden of disease is and will be therefore experienced in the developing world which, relative to the developed world, has extremely limited resources. The epidemic continues to spread throughout much of the developing world, while levels of HIV infection in the developed world are largely remaining constant, with the center seemingly moving more into marginalized groups such as the homeless, drug users, and other groups. A whole range of new drugs will soon be available to treat HIV/AIDS among those who can afford them. It is possible that AIDS may simply become manageable as a chronic illness in the west. Such drugs, however, will be prohibitively expensive for almost all people infected with HIV. Moreover, the side effects of these new drugs remain to be seen, and it is possible that individuals will develop resistance to the treatment. The author laments the lack of papers at the conference analyzing the impact of the epidemic and hopes to see more representation and consideration of the developing world at the next conference, to be held in Geneva in 1998.

  6. Fast and Accurate Simulation of the Cray XMT Multithreaded Supercomputer

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

    Villa, Oreste; Tumeo, Antonino; Secchi, Simone

    Irregular applications, such as data mining and analysis or graph-based computations, show unpredictable memory/network access patterns and control structures. Highly multithreaded architectures with large processor counts, like the Cray MTA-1, MTA-2 and XMT, appear to address their requirements better than commodity clusters. However, the research on highly multithreaded systems is currently limited by the lack of adequate architectural simulation infrastructures due to issues such as size of the machines, memory footprint, simulation speed, accuracy and customization. At the same time, Shared-memory MultiProcessors (SMPs) with multi-core processors have become an attractive platform to simulate large scale machines. In this paper, wemore » introduce a cycle-level simulator of the highly multithreaded Cray XMT supercomputer. The simulator runs unmodified XMT applications. We discuss how we tackled the challenges posed by its development, detailing the techniques introduced to make the simulation as fast as possible while maintaining a high accuracy. By mapping XMT processors (ThreadStorm with 128 hardware threads) to host computing cores, the simulation speed remains constant as the number of simulated processors increases, up to the number of available host cores. The simulator supports zero-overhead switching among different accuracy levels at run-time and includes a network model that takes into account contention. On a modern 48-core SMP host, our infrastructure simulates a large set of irregular applications 500 to 2000 times slower than real time when compared to a 128-processor XMT, while remaining within 10\\% of accuracy. Emulation is only from 25 to 200 times slower than real time.« less

  7. Ocean acidification and global warming impair shark hunting behaviour and growth.

    PubMed

    Pistevos, Jennifer C A; Nagelkerken, Ivan; Rossi, Tullio; Olmos, Maxime; Connell, Sean D

    2015-11-12

    Alterations in predation pressure can have large effects on trophically-structured systems. Modification of predator behaviour via ocean warming has been assessed by laboratory experimentation and metabolic theory. However, the influence of ocean acidification with ocean warming remains largely unexplored for mesopredators, including experimental assessments that incorporate key components of the assemblages in which animals naturally live. We employ a combination of long-term laboratory and mesocosm experiments containing natural prey and habitat to assess how warming and acidification affect the development, growth, and hunting behaviour in sharks. Although embryonic development was faster due to temperature, elevated temperature and CO2 had detrimental effects on sharks by not only increasing energetic demands, but also by decreasing metabolic efficiency and reducing their ability to locate food through olfaction. The combination of these effects led to considerable reductions in growth rates of sharks held in natural mesocosms with elevated CO2, either alone or in combination with higher temperature. Our results suggest a more complex reality for predators, where ocean acidification reduces their ability to effectively hunt and exert strong top-down control over food webs.

  8. High Throughput, Label-free Screening Small Molecule Compound Libraries for Protein-Ligands using Combination of Small Molecule Microarrays and a Special Ellipsometry-based Optical Scanner.

    PubMed

    Landry, James P; Fei, Yiyan; Zhu, X D

    2011-12-01

    Small-molecule compounds remain the major source of therapeutic and preventative drugs. Developing new drugs against a protein target often requires screening large collections of compounds with diverse structures for ligands or ligand fragments that exhibit sufficiently affinity and desirable inhibition effect on the target before further optimization and development. Since the number of small molecule compounds is large, high-throughput screening (HTS) methods are needed. Small-molecule microarrays (SMM) on a solid support in combination with a suitable binding assay form a viable HTS platform. We demonstrate that by combining an oblique-incidence reflectivity difference optical scanner with SMM we can screen 10,000 small-molecule compounds on a single glass slide for protein ligands without fluorescence labeling. Furthermore using such a label-free assay platform we can simultaneously acquire binding curves of a solution-phase protein to over 10,000 immobilized compounds, thus enabling full characterization of protein-ligand interactions over a wide range of affinity constants.

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

    Hobbs, R.E.

    In large facilities, successful energy management cannot be measured by a few projects, no matter how significant the energy savings. Large facilities today are comprised of extensive energy consuming systems. For every energy project developed, two more projects remain to be discovered. The successful energy manager is one who has completed ten projects, or twenty, or thirty, and is still finding more projects to do. Nothing is assumed to be as efficient as possible, and no part of any system is ignored. The successful energy manager is willing to take risks, not of being fired, but to use imagination, studymore » engineering theory, exercise common sense, develop concept designs, calculate savings, sell projects to management, control designers, study equipment performance, pre-select contractors, manage the contractor efforts, solve inherent problems along the way, and then optimize the project after acceptance when the designers and contractors all walk off. Once the successful energy manager establishes his credibility, his problem becomes finding enough time to get the projects rolling as he dreams them up. He sees what others do not. As they say in the North, only the lead dog sees new scenery.« less

  10. Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years

    PubMed Central

    Wang, Lingchong; Wang, Xiangyu; Wu, Hao; Liu, Rui

    2014-01-01

    Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits. PMID:25257786

  11. Harvesting of Chlorella sorokiniana by co-culture with the filamentous fungus Isaria fumosorosea: A potential sustainable feedstock for hydrothermal gasification.

    PubMed

    Mackay, Stephen; Gomes, Eduardo; Holliger, Christof; Bauer, Rolene; Schwitzguébel, Jean-Paul

    2015-06-01

    Despite recent advances in down-stream processing, production of microalgae remains substantially limited because of economical reasons. Harvesting and dewatering are the most energy-intensive processing steps in their production and contribute 20-30% of total operational cost. Bio-flocculation of microalgae by co-cultivation with filamentous fungi relies on the development of large structures that facilitate cost effective harvesting. A yet unknown filamentous fungus was isolated as a contaminant from a microalgal culture and identified as Isaria fumosorosea. Blastospores production was optimized in minimal medium and the development of pellets, possibly lichens, was followed when co-cultured with Chlorella sorokiniana under strict autotrophic conditions. Stable pellets (1-2mm) formed rapidly at pH 7-8, clearing the medium of free algal cells. Biomass was harvested with large inexpensive filters, generating wet slurry suitable for hydrothermal gasification. Nutrient rich brine from the aqueous phase of hydrothermal gasification supported growth of the fungus and may increase the process sustainability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Challenges in Improving Cochlear Implant Performance and Accessibility.

    PubMed

    Zeng, Fan-Gang

    2017-08-01

    Here I identify two gaps in cochlear implants that have been limiting their performance and acceptance. First, cochlear implant performance has remained largely unchanged, despite the number of publications tripling per decade in the last 30 years. Little has been done so far to address a fundamental limitation in the electrode-to-neuron interface, with the electrode size being a thousand times larger than the neuron diameter while the number of electrodes being a thousand times less. Both the small number and the large size of electrodes produce broad spatial activation and poor frequency resolution that limit current cochlear implant performance. Second, a similarly rapid growth in cochlear implant volume has not produced an expected decrease in unit price in the same period. The high cost contributes to low market penetration rate, which is about 20% in developed countries and less than 1% in developing countries. I will discuss changes needed in both research strategy and business practice to close the gap between prosthetic and normal hearing as well as that between haves and have-nots.

  13. An automated extinction and sky brightness monitor for the Indian Astronomical Observatory, Hanle

    NASA Astrophysics Data System (ADS)

    Sharma, Tarun Kumar; Parihar, Padmakar; Banyal, R. K.; Dar, Ajaz Ahmad; Kemkar, P. M. M.; Stanzin, Urgain; Anupama, G. C.

    2017-09-01

    We have developed a simple and portable device that makes precise and automated measurements of night sky extinction. Our instrument uses a commercially available telephoto lens for light collection, which is retrofitted to a custom-built telescope mount, a thermoelectrically cooled CCD for imaging, and a compact enclosure with electronic control to facilitate remote observations. The instrument is also capable of measuring the sky brightness and detecting the presence of thin clouds that otherwise would remain unnoticed. The measurements of sky brightness made by our simple device are more accurate than those made using a large telescope. Another capability of the device is that it can provide an instantaneous measurement of atmospheric extinction, which is extremely useful for exploring the nature of short-term extinction variation. The instrument was designed and developed primarily in order to characterize and investigate thoroughly the Indian Astronomical Observatory (IAO), Hanle for the establishment of India's future large-telescope project. The device was installed at the IAO, Hanle in 2014 May. In this paper, we present the instrument details and discuss the results of extinction data collected for about 250 nights.

  14. Bio-inspired wooden actuators for large scale applications.

    PubMed

    Rüggeberg, Markus; Burgert, Ingo

    2015-01-01

    Implementing programmable actuation into materials and structures is a major topic in the field of smart materials. In particular the bilayer principle has been employed to develop actuators that respond to various kinds of stimuli. A multitude of small scale applications down to micrometer size have been developed, but up-scaling remains challenging due to either limitations in mechanical stiffness of the material or in the manufacturing processes. Here, we demonstrate the actuation of wooden bilayers in response to changes in relative humidity, making use of the high material stiffness and a good machinability to reach large scale actuation and application. Amplitude and response time of the actuation were measured and can be predicted and controlled by adapting the geometry and the constitution of the bilayers. Field tests in full weathering conditions revealed long-term stability of the actuation. The potential of the concept is shown by a first demonstrator. With the sensor and actuator intrinsically incorporated in the wooden bilayers, the daily change in relative humidity is exploited for an autonomous and solar powered movement of a tracker for solar modules.

  15. Bio-Inspired Wooden Actuators for Large Scale Applications

    PubMed Central

    Rüggeberg, Markus; Burgert, Ingo

    2015-01-01

    Implementing programmable actuation into materials and structures is a major topic in the field of smart materials. In particular the bilayer principle has been employed to develop actuators that respond to various kinds of stimuli. A multitude of small scale applications down to micrometer size have been developed, but up-scaling remains challenging due to either limitations in mechanical stiffness of the material or in the manufacturing processes. Here, we demonstrate the actuation of wooden bilayers in response to changes in relative humidity, making use of the high material stiffness and a good machinability to reach large scale actuation and application. Amplitude and response time of the actuation were measured and can be predicted and controlled by adapting the geometry and the constitution of the bilayers. Field tests in full weathering conditions revealed long-term stability of the actuation. The potential of the concept is shown by a first demonstrator. With the sensor and actuator intrinsically incorporated in the wooden bilayers, the daily change in relative humidity is exploited for an autonomous and solar powered movement of a tracker for solar modules. PMID:25835386

  16. Streamlining Building Efficiency Evaluation with DOE's Asset Score Preview

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

    Goel, Supriya; Wang, Nora; Gonzalez, Juan

    2016-08-26

    Building Energy Asset Score (Asset Score), developed by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy (DOE), is a tool to help building owners and managers assess the efficiency of a building's energy-related systems and encourage investment in cost-effective improvements. The Asset Score uses an EnergyPlus model to provide a quick assessment of building energy performance with minimum user inputs of building characteristics and identifies upgrade opportunities. Even with a reduced set of user inputs, data collection remains a challenge for wide-spread adoption, especially when evaluating a large number of buildings. To address this, Asset Scoremore » Preview was developed to allow users to enter as few as seven building characteristics to quickly assess their buildings before a more in-depth analysis. A streamlined assessment from Preview to full Asset Score provides an easy entry point and also enables users who manage a large number of buildings to screen and prioritize buildings that can benefit most from a more detailed evaluation and possible energy efficiency upgrades without intensive data collection.« less

  17. Ocean acidification and global warming impair shark hunting behaviour and growth

    PubMed Central

    Pistevos, Jennifer C. A.; Nagelkerken, Ivan; Rossi, Tullio; Olmos, Maxime; Connell, Sean D.

    2015-01-01

    Alterations in predation pressure can have large effects on trophically-structured systems. Modification of predator behaviour via ocean warming has been assessed by laboratory experimentation and metabolic theory. However, the influence of ocean acidification with ocean warming remains largely unexplored for mesopredators, including experimental assessments that incorporate key components of the assemblages in which animals naturally live. We employ a combination of long-term laboratory and mesocosm experiments containing natural prey and habitat to assess how warming and acidification affect the development, growth, and hunting behaviour in sharks. Although embryonic development was faster due to temperature, elevated temperature and CO2 had detrimental effects on sharks by not only increasing energetic demands, but also by decreasing metabolic efficiency and reducing their ability to locate food through olfaction. The combination of these effects led to considerable reductions in growth rates of sharks held in natural mesocosms with elevated CO2, either alone or in combination with higher temperature. Our results suggest a more complex reality for predators, where ocean acidification reduces their ability to effectively hunt and exert strong top-down control over food webs. PMID:26559327

  18. Improving detection of patient deterioration in the general hospital ward environment.

    PubMed

    Vincent, Jean-Louis; Einav, Sharon; Pearse, Rupert; Jaber, Samir; Kranke, Peter; Overdyk, Frank J; Whitaker, David K; Gordo, Federico; Dahan, Albert; Hoeft, Andreas

    2018-05-01

    : Patient monitoring on low acuity general hospital wards is currently based largely on intermittent observations and measurements of simple variables, such as blood pressure and temperature, by nursing staff. Often several hours can pass between such measurements and patient deterioration can go unnoticed. Moreover, the integration and interpretation of the information gleaned through these measurements remains highly dependent on clinical judgement. More intensive monitoring, which is commonly used in peri-operative and intensive care settings, is more likely to lead to the early identification of patients who are developing complications than is intermittent monitoring. Early identification can trigger appropriate management, thereby reducing the need for higher acuity care, reducing hospital lengths of stay and admission costs and even, at times, improving survival. However, this degree of monitoring has thus far been considered largely inappropriate for general hospital ward settings due to device costs and the need for staff expertise in data interpretation. In this review, we discuss some developing options to improve patient monitoring and thus detection of deterioration in low acuity general hospital wards.

  19. A survey of the rock record of reptilian ontogeny.

    PubMed

    Delfino, Massimo; Sánchez-Villagra, Marcelo R

    2010-06-01

    Given the large diversity and long stratigraphical range of fossil reptiles, their development is a fundamental aspect of the evolution of ontogeny in vertebrates. Eggs, juveniles, embryos and growth series document different aspects of fossilized ontogenies. About three-fifths of the more than 850 available publications on these topics concern dinosaurs. Non-invasive imaging techniques have facilitated the study of embryos in ovo. Examination of ontogenetic trajectories is used to establish criteria to identify fossil growth series and solve taxonomic issues. Many morphological innovations in reptilian skeletal structures are associated with growth heterochronic changes, whereas sequence heterochronic changes remain largely unstudied but are a potential avenue of research. Relative age assessments via not only palaeohistology but also comparative anatomy have been used to reconstruct life history patterns in fossil archosaurs. Several fossil marine reptiles evolved viviparity convergently. Extinct adult phenotypes can reveal information on development, as in the discovery of polydactyly in diapsids, the examination of vertebral number evolution, and its relation to somitgenesis and Hox-gene boundaries, and signs of tissue regeneration provided by anatomical peculiarities following caudal autotomy. (c) 2009 Elsevier Ltd. All rights reserved.

  20. PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia.

    PubMed

    Liu, Wenying Angela; Chen, She; Li, Zhizhong; Lee, Choong Heon; Mirzaa, Ghayda; Dobyns, William B; Ross, M Elizabeth; Zhang, Jiangyang; Shi, Song-Hai

    2018-06-01

    Proper organization and orderly mitosis of radial glial progenitors (RGPs) drive the formation of a laminated mammalian cortex in the correct size. However, the molecular underpinnings of the intricate process remain largely unclear. Here we show that RGP behavior and cortical development are controlled by temporally distinct actions of partitioning-defective 3 (PARD3) in concert with dynamic HIPPO signaling. RGPs lacking PARD3 exhibit developmental stage-dependent abnormal switches in division mode, resulting in an initial overproduction of RGPs located largely outside the ventricular zone at the expense of deep-layer neurons. Ectopically localized RGPs subsequently undergo accelerated and excessive neurogenesis, leading to the formation of an enlarged cortex with massive heterotopia and increased seizure susceptibility. Simultaneous removal of HIPPO pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) suppresses cortical enlargement and heterotopia formation. These results define a dynamic regulatory program of mammalian cortical development and highlight a progenitor origin of megalencephaly with ribbon heterotopia and epilepsy. © 2018 Liu et al.; Published by Cold Spring Harbor Laboratory Press.

  1. Turbulence characteristics of velocity and scalars in an internal boundary-layer above a lake

    NASA Astrophysics Data System (ADS)

    Sahlee, E.; Rutgersson, A.; Podgrajsek, E.

    2012-12-01

    We analyze turbulence measurements, including methane, from a small island in a Swedish lake. The turbulence structure was found to be highly influenced by the surrounding land during daytime. Variance spectra of both horizontal velocity and scalars during both unstable and stable stratification displayed a low frequency peak. The energy at lower frequencies displayed a daily variation, increasing in the morning and decreasing in the afternoon. We interpret this behavior as a sign of spectral lag, where the low frequency energy, large eddies, originate from the convective boundary layer above the surrounding land. When the air is advected over the lake the small eddies rapidly equilibrates with new surface forcing. However, the larger eddies remain for an appreciable distance and influence the turbulence in the developing lake boundary layer. The variance of the horizontal velocity is increased by these large eddies however, momentum fluxes and scalar variances and fluxes appear unaffected. The drag coefficient, Stanton number and Dalton number used to parameterize the momentum flux, heat flux and latent heat flux respectively all compare very well with parameterizations developed for open ocean conditions.

  2. Guidelines for the recognition of cemetery remains in Greece.

    PubMed

    Eliopoulos, Constantine; Moraitis, Konstantinos; Reyes, Federico; Spiliopoulou, Chara; Manolis, Sotiris

    2011-06-01

    Forensic pathologists frequently consult anthropologists for the identification of skeletonized human remains. These remains may be the result of criminal activity or remains that were unearthed because of erosion, or during construction projects. In some cases, human remains that had been previously buried in a cemetery may be the subject of a forensic investigation. Early recognition of cemetery remains prevents unnecessary efforts and conserves precious resources. One of the key characteristics of cemetery remains is the presence of embalmed tissue. However, there are countries where embalming is not a common practice, and other clues must be sought for identifying previously buried remains. Current funerary customs in Greece and, in particular, the tradition of exhumations result in a large number of misplaced human remains. The present study presents examples of cemetery remains from Greece and offers guidelines for recognizing changes on skeletal remains that may be indicative of a cemetery origin. Location of discovery, condition of the remains, and the types of associated artifacts are all factors that aid forensic anthropologists in identifying cemetery remains.

  3. Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials.

    PubMed

    Larson, Gregg S; Carey, Cate; Grarup, Jesper; Hudson, Fleur; Sachi, Karen; Vjecha, Michael J; Gordin, Fred

    2016-04-01

    Randomized clinical trials are widely recognized as essential to address worldwide clinical and public health research questions. However, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost. We identify approaches and practices for large, publicly funded, international trials that reduce cost without compromising data integrity and recommend an approach to cost reporting that permits comparison of clinical trials. We describe the organizational and financial characteristics of The International Network for Strategic Initiatives in Global HIV Trials, an infectious disease research network that conducts multiple, large, long-term, international trials, and examine challenges associated with simple and streamlined governance and an infrastructure and financial management model that is based on performance, transparency, and accountability. It is possible to reduce costs of participants' follow-up and not compromise clinical trial quality or integrity. The International Network for Strategic Initiatives in Global HIV Trials network has successfully completed three large HIV trials using cost-efficient practices that have not adversely affected investigator enthusiasm, accrual rates, loss-to-follow-up, adherence to the protocol, and completion of data collection. This experience is relevant to the conduct of large, publicly funded trials in other disease areas, particularly trials dependent on international collaborations. New approaches, or creative adaption of traditional clinical trial infrastructure and financial management tools, can render large, international clinical trials more cost-efficient by emphasizing structural simplicity, minimal up-front costs, payments for performance, and uniform algorithms and fees-for-service, irrespective of location. However, challenges remain. They include institutional resistance to financial change, growing trial complexity, and the difficulty of sustaining network infrastructure absent stable research work. There is also a need for more central monitoring, improved and harmonized regulations, and a widely applied metric for measuring and comparing cost efficiency in clinical trials. ClinicalTrials.gov is recommended as a location where standardized trial cost information could be made publicly accessible. © The Author(s) 2016.

  4. State of the Art in Large-Scale Soil Moisture Monitoring

    NASA Technical Reports Server (NTRS)

    Ochsner, Tyson E.; Cosh, Michael Harold; Cuenca, Richard H.; Dorigo, Wouter; Draper, Clara S.; Hagimoto, Yutaka; Kerr, Yan H.; Larson, Kristine M.; Njoku, Eni Gerald; Small, Eric E.; hide

    2013-01-01

    Soil moisture is an essential climate variable influencing land atmosphere interactions, an essential hydrologic variable impacting rainfall runoff processes, an essential ecological variable regulating net ecosystem exchange, and an essential agricultural variable constraining food security. Large-scale soil moisture monitoring has advanced in recent years creating opportunities to transform scientific understanding of soil moisture and related processes. These advances are being driven by researchers from a broad range of disciplines, but this complicates collaboration and communication. For some applications, the science required to utilize large-scale soil moisture data is poorly developed. In this review, we describe the state of the art in large-scale soil moisture monitoring and identify some critical needs for research to optimize the use of increasingly available soil moisture data. We review representative examples of 1) emerging in situ and proximal sensing techniques, 2) dedicated soil moisture remote sensing missions, 3) soil moisture monitoring networks, and 4) applications of large-scale soil moisture measurements. Significant near-term progress seems possible in the use of large-scale soil moisture data for drought monitoring. Assimilation of soil moisture data for meteorological or hydrologic forecasting also shows promise, but significant challenges related to model structures and model errors remain. Little progress has been made yet in the use of large-scale soil moisture observations within the context of ecological or agricultural modeling. Opportunities abound to advance the science and practice of large-scale soil moisture monitoring for the sake of improved Earth system monitoring, modeling, and forecasting.

  5. Waving of filaments induced by molecular motors

    NASA Astrophysics Data System (ADS)

    de Canio, Gabriele; Lauga, Eric; Goldstein, Raymond E.

    2017-11-01

    In many cellular phenomena, for example cytoplasmic streaming, molecular motors translocate along microtubules carrying cargoes which entrain fluid. The piconewton forces that motors produce can be sufficient to bend or buckle the filaments. When large numbers of such forced filaments interact through the surrounding fluid, as in particular stages of oocyte development in Drosophila melanogaster, complex dynamics are observed, but the mechanism underlying them has remained unclear. By using a combination of theory and numerical simulations, we study a simplified microtubules-molecular motor system in a viscous fluid and show that it can capture the wave-like filament motion dynamics observed in experiments.

  6. Zilsel's Thesis, Maritime Culture, and Iberian Science in Early Modern Europe.

    PubMed

    Leitão, Henrique; Sánchez, Antonio

    2017-01-01

    Zilsel's thesis on the artisanal origins of modern science remains one of the most original proposals about the emergence of scientific modernity. We propose to inspect the scientific developments in Iberia in the early modern period using Zilsel's ideas as a guideline. Our purpose is to show that his ideas illuminate the situation in Iberia but also that the Iberian case is a remarkable illustration of Zilsel's thesis. Furthermore, we argue that Zilsel's thesis is essentially a sociological explanation that cannot be applied to isolated cases; its use implies global events that involve extended societies over large periods of time.

  7. Specialized metabolites from the microbiome in health and disease

    PubMed Central

    Sharon, Gil; Garg, Neha; Debelius, Justine; Knight, Rob; Dorrestein, Pieter C.; Mazmanian, Sarkis K.

    2015-01-01

    The microbiota, and the genes that comprise its microbiome, play key roles in human health. Host-microbe interactions affect immunity, metabolism, development, and behavior, and dysbiosis of gut bacteria contributes to disease. Despite advances in correlating changes in the microbiota with various conditions, specific mechanisms of host-microbiota signaling remain largely elusive. We discuss the synthesis of microbial metabolites, their absorption, and potential physiological effects on the host. We propose that the effects of specialized metabolites may explain present knowledge gaps linking the gut microbiota to biological host mechanisms during initial colonization, and in health and disease. PMID:25440054

  8. KSC-2013-3617

    NASA Image and Video Library

    2013-09-19

    CAPE CANAVERAL, Fla. – At Launch Pad 39B at NASA’s Kennedy Space Center in Florida, a large bulldozer is used to remove the remaining portions of the flame trench deflector that was located below and between the left and right crawlerway tracks. Pad B is being refurbished to support NASA’s Space Launch System and other launch vehicles. The Ground Systems Development and Operations, or GSDO, Program at Kennedy is leading the center’s transformation to safely handle a variety of rockets and spacecraft. For more information about GSDO, visit: http://go.nasa.gov/groundsystems. Photo credit: NASA/Jim Grossman

  9. Exploring Innovation Capabilities of Hospital CIOs: An Empirical Assessment.

    PubMed

    Esdar, Moritz; Liebe, Jan-David; Weiß, Jan-Patrick; Hübner, Ursula

    2017-01-01

    Hospital CIOs play a central role in the adoption of innovative health IT. Until now, it remained unclear which particular conditions constitute their capability to innovate in terms of intrapersonal as well as organisational factors. An inventory of 20 items was developed to capture these conditions and examined by analysing data obtained from 164 German hospital CIOs. Principal component analysis resulted in three internally consistent components that constitute large portions of the CIOs innovation capability: organisational innovation culture, entrepreneurship personality and openness towards users. Results were used to build composite indicators that allow further evaluations.

  10. Theory-Based Parameterization of Semiotics for Measuring Pre-literacy Development

    NASA Astrophysics Data System (ADS)

    Bezruczko, N.

    2013-09-01

    A probabilistic model was applied to problem of measuring pre-literacy in young children. First, semiotic philosophy and contemporary cognition research were conceptually integrated to establish theoretical foundations for rating 14 characteristics of children's drawings and narratives (N = 120). Then ratings were transformed with a Rasch model, which estimated linear item parameter values that accounted for 79 percent of rater variance. Principle Components Analysis of item residual matrix confirmed variance remaining after item calibration was largely unsystematic. Validation analyses found positive correlations between semiotic measures and preschool literacy outcomes. Practical implications of a semiotics dimension for preschool practice were discussed.

  11. Soundscapes and Larval Settlement: Characterizing the Stimulus from a Larval Perspective.

    PubMed

    Lillis, Ashlee; Eggleston, David B; Bohnenstiehl, DelWayne R

    2016-01-01

    There is growing evidence that underwater sounds serve as a cue for the larvae of marine organisms to locate suitable settlement habitats; however, the relevant spatiotemporal scales of variability in habitat-related sounds and how this variation scales with larval settlement processes remain largely uncharacterized, particularly in estuarine habitats. Here, we provide an overview of the approaches we have developed to characterize an estuarine soundscape as it relates to larval processes, and a conceptual framework is provided for how habitat-related sounds may influence larval settlement, using oyster reef soundscapes as an example.

  12. Finding the engram.

    PubMed

    Josselyn, Sheena A; Köhler, Stefan; Frankland, Paul W

    2015-09-01

    Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram.

  13. The hubble constant.

    PubMed

    Huchra, J P

    1992-04-17

    The Hubble constant is the constant of proportionality between recession velocity and distance in the expanding universe. It is a fundamental property of cosmology that sets both the scale and the expansion age of the universe. It is determined by measurement of galaxy The Hubble constant is the constant of proportionality between recession velocity and development of new techniques for the measurements of galaxy distances, both calibration uncertainties and debates over systematic errors remain. Current determinations still range over nearly a factor of 2; the higher values favored by most local measurements are not consistent with many theories of the origin of large-scale structure and stellar evolution.

  14. Computational Simulation of Large Droplet Icing

    DOT National Transportation Integrated Search

    1996-01-01

    Certification for flight into known icing remains one of the more challenging goals for aircraft manufacturers. This activity has been further complicated by the current interest in large droplet icing. Due to the lack of data available on the meteor...

  15. An interactive web application for the dissemination of human systems immunology data.

    PubMed

    Speake, Cate; Presnell, Scott; Domico, Kelly; Zeitner, Brad; Bjork, Anna; Anderson, David; Mason, Michael J; Whalen, Elizabeth; Vargas, Olivia; Popov, Dimitry; Rinchai, Darawan; Jourde-Chiche, Noemie; Chiche, Laurent; Quinn, Charlie; Chaussabel, Damien

    2015-06-19

    Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

  16. Influence from Surrounding Land on the Turbulence Measurements Above a Lake

    NASA Astrophysics Data System (ADS)

    Sahlée, Erik; Rutgersson, Anna; Podgrajsek, Eva; Bergström, Hans

    2014-02-01

    Turbulence measurements taken at a Swedish lake are analyzed. Although the measurements took place over a relatively large lake with several km of undisturbed fetch, the turbulence structure was found to be highly influenced by the surrounding land during daytime. Variance spectra of both horizontal velocity and scalars during both unstable and stable stratification displayed a low frequency peak. The energy at lower frequencies showed a daily variation, increasing in the morning and decreasing in the afternoon. This behaviour is explained by spectral lag, where the low frequency energy due to large eddies that originate from the convective boundary layer above the surrounding land. When the air is advected over the lake the small eddies rapidly equilibrate with the new surface forcing. However, the large eddies remain for an appreciable distance and influence the turbulence in the developing lake boundary layer. The variances of the horizontal velocity and scalars are increased by these large eddies, while the turbulent fluxes are mainly unaffected. The drag coefficient, Stanton number and Dalton number used to parametrize the momentum flux, heat flux and latent heat flux respectively all compare well with current parametrizations developed for open sea conditions. The diurnal cycle of the partial pressure of methane, pCH4, observed at this site is closely related to the diurnal cycle of the lake-air methane flux. An idealized two-dimensional model simulation of the boundary layer at a lake site indicates that the strong response of pCH4 to the surface methane flux is due to the shallow internal boundary layer that develops above the lake, allowing methane to accumulate in a relatively small volume.

  17. Quest: A Hybrid Faculty Teaching and Learning Community

    ERIC Educational Resources Information Center

    Joseph, Siny; Oh, Jung; Ackerman, Patricia

    2018-01-01

    Faculty members often collaborate on research and service projects, but teaching remains a relatively solitary activity (Gizir & Simsek, 2005 ; Ramsden, 1998 ). While students attend classes taught by various faculty members, faculty members remain largely unaware of the innovative and pedagogical improvements in teaching made by their…

  18. Diffusion blotting: a rapid and simple method for production of multiple blots from a single gel.

    PubMed

    Olsen, Ingrid; Wiker, Harald G

    2015-01-01

    A very simple and fast method for diffusion blotting of proteins from precast SDS-PAGE gels on a solid plastic support was developed. Diffusion blotting for 3 min gives a quantitative transfer of 10 % compared to 1-h electroblotting. For each subsequent blot from the same gel a doubling of transfer time is necessary to obtain the same amount of protein onto each blot. High- and low-molecular-weight components are transferred equally efficiently when compared to electroblotting. However, both methods do give a higher total transfer of the low-molecular-weight proteins compared to the large proteins. The greatest advantage of diffusion blotting is that several blots can be made from each lane, thus enabling testing of multiple antisera on virtually identical blots. The gel remains on the plastic support, which prevents it from stretching or shrinking. This ensures identical blots and facilitates more reliable molecular weight determination. Furthermore the proteins remaining in the gel can be stained with Coomassie Brilliant Blue or other methods for exact and easy comparison with the developed blots. These advantages make diffusion blotting the method of choice when quantitative protein transfer is not required.

  19. Pulmonary Hypertension and Vascular Abnormalities in Bronchopulmonary Dysplasia

    PubMed Central

    Mourani, Peter M.; Abman, Steven H.

    2015-01-01

    Advances in the care of preterm infants have improved survival of infants born at earlier gestational ages. Yet, these infants remain at risk for the chronic lung disease of infancy, bronchopulmonary dysplasia (BPD), which results in prolonged need for supplemental oxygen, recurrent respiratory exacerbations, and exercise intolerance. Recent investigations have highlighted the important contribution of the developing pulmonary circulation to lung development, demonstrating that these infants are also at risk for pulmonary vascular disease (PVD), including pulmonary hypertension (PH) and pulmonary vascular abnormalities, which contributes significantly to morbidity and mortality. In the past few years, several epidemiological studies have delineated the incidence of PH in preterm infants and the impact on outcomes. However, these studies have also highlighted gaps in our understanding of PVD in BPD, including universally accepted definitions, approaches to diagnosis and treatment, and patient outcomes. Associated pulmonary vascular and cardiac abnormalities are increasingly recognized complications contributing to PH in these infants, but incidence of these lesions and degree of contribution to disease remains unknown. Therapeutic strategies for PVD in BPD are largely untested, but recent evidence presents the rationale for the approach to diagnosis and treatment of BPD infants with PH that can be evaluated in future studies. PMID:26593082

  20. Species, gender, and identity: cracking petrels' sociochemical code.

    PubMed

    Mardon, Jérôme; Saunders, Sandra M; Anderson, Marti J; Couchoux, Charline; Bonadonna, Francesco

    2010-05-01

    Avian chemosignaling remains relatively unexplored, but its potential importance in birds' social behaviors is becoming recognized. Procellariiform seabirds provide particularly appropriate models for investigating these topics as they possess a well-developed olfactory system and unequalled associated capabilities. We present here results from a detailed chemical examination of the uropygial secretions (the main source of avian exogenous chemicals) from 2 petrel species, Antarctic prions and blue petrels. Using gas chromatography-mass spectrometry techniques and recently developed multivariate tools, we demonstrate that the secretions contain critical socioecological information such as species, gender, and individual identity. Importantly, these chemosignals correlate with some of the birds' olfactory behaviors demonstrated in the field. The molecules found to be associated with social information were essentially large unsaturated compounds, suggesting that these may be precursors of, or correlates to the actual airborne signals. Although the species-specific chemosignal may be involved in interspecific competition at the breeding grounds, the role of the sexually specific chemosignal remains unclear. The existence of individually specific signals (i.e., chemical signatures) in these birds has important implications for processes such as individual recognition and genetically based mate choice already suspected for this group. Our results open promising avenues of research for the study of avian chemical communication.

  1. Marine and freshwater microplastic research in South Africa.

    PubMed

    Verster, Carina; Minnaar, Karin; Bouwman, Hindrik

    2017-05-01

    South Africa has a vibrant plastics manufacturing industry, but recycling is limited and insufficient with a notable proportion of the unmanaged waste entering the environment. South Africa is a developing country with microplastics research in its inception. Very little is known about freshwater microplastics, and studies on South African marine microplastics are limited but actively being pursued. In a water-scarce country, protection of freshwater resources remains a priority, but in the face of other socioeconomic issues (poverty, unemployment, and HIV/AIDS), it receives insufficiently effective attention. The full impact and risks of microplastics pollution in water is yet to be discovered. The risks may be enhanced in a developing country where many communities remain largely dependent on the land and natural waters. With South Africa being a water-scarce country, the quality of its aquatic resources is at an even greater risk with an assumed increasing background of microplastics, emphasizing the need for further research. A South African Water Research Commission-funded project is being undertaken to derive research priorities, but there is an immediate need for improved recycling and waste management. Integr Environ Assess Manag 2017;13:533-535. © 2017 SETAC. © 2017 SETAC.

  2. The Density Code for the Development of a Vaccine?

    PubMed Central

    Cheng, Wei

    2016-01-01

    The development of prophylactic vaccines remains largely empirical in nature and rarely have general rules been applied in the strategic decision and the formulation of a viral vaccine. Currently there are a total of 15 virus agents from 12 unique virus families with vaccines licensed by the US Food and Drug Administration. Extensive structural information on these viral particles and potential mechanisms of protection are available for the majority of these virus pathogens and their respective vaccines. Here I review the quantitative features of these viral surface antigens in relation to the molecular mechanisms of B cell activation, and point out a potential correlation between the density of immunogenic proteins displayed on the surface of the vaccine antigen carrier and the success of a vaccine. These features help us understand the humoral immunity induced by viral vaccines on a quantitative ground and re-emphasize the importance of antigen density on the activation of the immune system. Although the detailed mechanisms behind this phenomenon remain to be explored, it implies that both the size of antigen carriers and the density of immunogenic proteins displayed on these carriers are important parameters that may need to be optimized for the formulation of a vaccine. PMID:27649885

  3. Cross-talk between virus and host innate immunity in pediatric HIV-1 infection and disease progression.

    PubMed

    Freguja, Riccardo; Gianesin, Ketty; Zanchetta, Marisa; De Rossi, Anita

    2012-07-01

    Variability in the susceptibility to HIV-1 infection and disease progression depends on both virus and host determinants. Some exposed individuals remain HIV-1-uninfected and HIV-1-infected subjects develop disease at varying intervals with a small percentage remaining long-term non-progressors. As innate immunity is the earliest response to microbial entry and injury, host factors that impact innate immunity may play a role in viral infectivity and pathogenesis. In the pediatric population the interactions between the virus and the host may be of particular relevance due to the still developing adaptive immune system. Data indicate that genetic variants of defensins and Toll-Like Receptors (TLRs), key elements of innate immunity, play a role in mother-to-child transmission (MTCT) of HIV-1, and in the outcome of pediatric HIV-1 disease. Although the mechanisms by which these genetic variants influence HIV-1 interactions with the host are still largely unknown, defensins and TLRs, along with their link with regulatory T cells (Tregs), may play a critical role in the onset and persistence of immune activation, a hallmark of HIV-1 disease.

  4. Horticultural Performance of Eight American Elderberry Genotypes at Three Missouri Locations

    PubMed Central

    Thomas, A.L.; Byers, P.L.; Avery, J.D.; Kaps, M.; Gu, S.

    2016-01-01

    American elderberry (Sambucus nigra subsp. canadensis) is being increasingly cultivated in North America for its edible and medicinal fruit and flowers, yet remains largely undeveloped as a horticultural crop. Productive genotypes with desirable horticultural attributes, including disease and insect resistance, precocity, uniform fruit ripening, and large berry size are needed in order to advance the commercial production of elderberries. A four-year study of eight elderberry genotypes was established in 2008 at three diverse Missouri (USA) locations. Phenology, plant morphology, pest susceptibility, productivity, and fruit characteristics data were collected over three growing seasons, 2009–2011. Significant differences for most phenological, horticultural, and fruit juice characteristics were observed among the three sites, three years, and eight genotypes. The genotype ‘Ozark’ was the earliest to break bud, produced fruit with high levels of soluble solids, and out-yielded most other genotypes at the three sites over the three-year study. None of the new genotypes produced berries as large as or larger than the standard ‘York’ which is known for its large fruit. Some of the genotypes tested, especially ‘Ozark’ show promise as potential cultivars and as breeding stock for further development of elderberry as a commercially-viable horticultural crop. PMID:27158183

  5. Horticultural Performance of Eight American Elderberry Genotypes at Three Missouri Locations.

    PubMed

    Thomas, A L; Byers, P L; Avery, J D; Kaps, M; Gu, S

    2015-01-12

    American elderberry ( Sambucus nigra subsp. canadensis ) is being increasingly cultivated in North America for its edible and medicinal fruit and flowers, yet remains largely undeveloped as a horticultural crop. Productive genotypes with desirable horticultural attributes, including disease and insect resistance, precocity, uniform fruit ripening, and large berry size are needed in order to advance the commercial production of elderberries. A four-year study of eight elderberry genotypes was established in 2008 at three diverse Missouri (USA) locations. Phenology, plant morphology, pest susceptibility, productivity, and fruit characteristics data were collected over three growing seasons, 2009-2011. Significant differences for most phenological, horticultural, and fruit juice characteristics were observed among the three sites, three years, and eight genotypes. The genotype 'Ozark' was the earliest to break bud, produced fruit with high levels of soluble solids, and out-yielded most other genotypes at the three sites over the three-year study. None of the new genotypes produced berries as large as or larger than the standard 'York' which is known for its large fruit. Some of the genotypes tested, especially 'Ozark' show promise as potential cultivars and as breeding stock for further development of elderberry as a commercially-viable horticultural crop.

  6. The long-term dynamics of mortality benefits from improved water and sanitation in less developed countries.

    PubMed

    Jeuland, Marc A; Fuente, David E; Ozdemir, Semra; Allaire, Maura C; Whittington, Dale

    2013-01-01

    The problem of inadequate access to water, sanitation and hygiene (WASH) in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals), largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975-2050) and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa), if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed.

  7. The Long-Term Dynamics of Mortality Benefits from Improved Water and Sanitation in Less Developed Countries

    PubMed Central

    Jeuland, Marc A.; Fuente, David E.; Ozdemir, Semra; Allaire, Maura C.; Whittington, Dale

    2013-01-01

    The problem of inadequate access to water, sanitation and hygiene (WASH) in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals), largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975–2050) and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa), if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed. PMID:24116011

  8. Childhood growth, schooling, and cognitive development: further evidence from the Young Lives study.

    PubMed

    Fink, Günther; Rockers, Peter C

    2014-07-01

    A growing literature has linked early childhood growth to later-life cognition and schooling outcomes in developing countries. Although existing evidence suggests that children's ability to recover from early growth delays in later childhood is limited, longitudinal studies on the persistence and risk of growth faltering beyond age 5 y remain scarce. Using longitudinal data recently collected from 4 developing countries as part of the Young Lives study, we investigated catch-up growth in children between the ages of 8 and 15 y and the effects of growth during this late-childhood and early-adolescence period on schooling and developmental outcomes. We analyzed the associations between children's physical growth and development by using longitudinal data from 3327 children aged 8-15 y collected in Ethiopia, India, Peru, and Vietnam as part of the Young Lives project. The study yielded 2 main results. First, 36% of children stunted at age 8 y managed to catch up with their peers by age 15 y, and those who caught up had smaller deficits in cognitive scores than did children who remained stunted. Second, physical growth faltering was not restricted to early childhood but rather affected a substantial share of children in the 8-15-y age range, with large negative consequences for cognition and schooling outcomes. The results from this study suggest that child development in developing countries is a dynamic process offering continued opportunities for children to catch up during adolescence and sustained risks for children to fall behind in their developmental trajectories. © 2014 American Society for Nutrition.

  9. New U.S. Geological Survey Method for the Assessment of Reserve Growth

    USGS Publications Warehouse

    Klett, Timothy R.; Attanasi, E.D.; Charpentier, Ronald R.; Cook, Troy A.; Freeman, P.A.; Gautier, Donald L.; Le, Phuong A.; Ryder, Robert T.; Schenk, Christopher J.; Tennyson, Marilyn E.; Verma, Mahendra K.

    2011-01-01

    Reserve growth is defined as the estimated increases in quantities of crude oil, natural gas, and natural gas liquids that have the potential to be added to remaining reserves in discovered accumulations through extension, revision, improved recovery efficiency, and additions of new pools or reservoirs. A new U.S. Geological Survey method was developed to assess the reserve-growth potential of technically recoverable crude oil and natural gas to be added to reserves under proven technology currently in practice within the trend or play, or which reasonably can be extrapolated from geologically similar trends or plays. This method currently is in use to assess potential additions to reserves in discovered fields of the United States. The new approach involves (1) individual analysis of selected large accumulations that contribute most to reserve growth, and (2) conventional statistical modeling of reserve growth in remaining accumulations. This report will focus on the individual accumulation analysis. In the past, the U.S. Geological Survey estimated reserve growth by statistical methods using historical recoverable-quantity data. Those statistical methods were based on growth rates averaged by the number of years since accumulation discovery. Accumulations in mature petroleum provinces with volumetrically significant reserve growth, however, bias statistical models of the data; therefore, accumulations with significant reserve growth are best analyzed separately from those with less significant reserve growth. Large (greater than 500 million barrels) and older (with respect to year of discovery) oil accumulations increase in size at greater rates late in their development history in contrast to more recently discovered accumulations that achieve most growth early in their development history. Such differences greatly affect the statistical methods commonly used to forecast reserve growth. The individual accumulation-analysis method involves estimating the in-place petroleum quantity and its uncertainty, as well as the estimated (forecasted) recoverability and its respective uncertainty. These variables are assigned probabilistic distributions and are combined statistically to provide probabilistic estimates of ultimate recoverable quantities. Cumulative production and remaining reserves are then subtracted from the estimated ultimate recoverable quantities to provide potential reserve growth. In practice, results of the two methods are aggregated to various scales, the highest of which includes an entire country or the world total. The aggregated results are reported along with the statistically appropriate uncertainties.

  10. Partition-of-unity finite-element method for large scale quantum molecular dynamics on massively parallel computational platforms

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

    Pask, J E; Sukumar, N; Guney, M

    2011-02-28

    Over the course of the past two decades, quantum mechanical calculations have emerged as a key component of modern materials research. However, the solution of the required quantum mechanical equations is a formidable task and this has severely limited the range of materials systems which can be investigated by such accurate, quantum mechanical means. The current state of the art for large-scale quantum simulations is the planewave (PW) method, as implemented in now ubiquitous VASP, ABINIT, and QBox codes, among many others. However, since the PW method uses a global Fourier basis, with strictly uniform resolution at all points inmore » space, and in which every basis function overlaps every other at every point, it suffers from substantial inefficiencies in calculations involving atoms with localized states, such as first-row and transition-metal atoms, and requires substantial nonlocal communications in parallel implementations, placing critical limits on scalability. In recent years, real-space methods such as finite-differences (FD) and finite-elements (FE) have been developed to address these deficiencies by reformulating the required quantum mechanical equations in a strictly local representation. However, while addressing both resolution and parallel-communications problems, such local real-space approaches have been plagued by one key disadvantage relative to planewaves: excessive degrees of freedom (grid points, basis functions) needed to achieve the required accuracies. And so, despite critical limitations, the PW method remains the standard today. In this work, we show for the first time that this key remaining disadvantage of real-space methods can in fact be overcome: by building known atomic physics into the solution process using modern partition-of-unity (PU) techniques in finite element analysis. Indeed, our results show order-of-magnitude reductions in basis size relative to state-of-the-art planewave based methods. The method developed here is completely general, applicable to any crystal symmetry and to both metals and insulators alike. We have developed and implemented a full self-consistent Kohn-Sham method, including both total energies and forces for molecular dynamics, and developed a full MPI parallel implementation for large-scale calculations. We have applied the method to the gamut of physical systems, from simple insulating systems with light atoms to complex d- and f-electron systems, requiring large numbers of atomic-orbital enrichments. In every case, the new PU FE method attained the required accuracies with substantially fewer degrees of freedom, typically by an order of magnitude or more, than the current state-of-the-art PW method. Finally, our initial MPI implementation has shown excellent parallel scaling of the most time-critical parts of the code up to 1728 processors, with clear indications of what will be required to achieve comparable scaling for the rest. Having shown that the key remaining disadvantage of real-space methods can in fact be overcome, the work has attracted significant attention: with sixteen invited talks, both domestic and international, so far; two papers published and another in preparation; and three new university and/or national laboratory collaborations, securing external funding to pursue a number of related research directions. Having demonstrated the proof of principle, work now centers on the necessary extensions and optimizations required to bring the prototype method and code delivered here to production applications.« less

  11. Signaling through the TGF Beta-Activin Receptors ALK4/5/7 Regulates Testis Formation and Male Germ Cell Development

    PubMed Central

    Stringer, Jessica M.; van den Bergen, Jocelyn A.; Wilhelm, Dagmar; Sinclair, Andrew H.; Western, Patrick S.

    2013-01-01

    The developing testis provides an environment that nurtures germ cell development, ultimately ensuring spermatogenesis and fertility. Impacts on this environment are considered to underlie aberrant germ cell development and formation of germ cell tumour precursors. The signaling events involved in testis formation and male fetal germ cell development remain largely unknown. Analysis of knockout mice lacking single Tgfβ family members has indicated that Tgfβ's are not required for sex determination. However, due to functional redundancy, it is possible that additional functions for these ligands in gonad development remain to be discovered. Using FACS purified gonadal cells, in this study we show that the genes encoding Activin's, TGFβ's, Nodal and their respective receptors, are expressed in sex and cell type specific patterns suggesting particular roles in testis and germ cell development. Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGFβ signaling is required for testis cord formation during the critical testis-determining period. We also show that signaling through the Activin/NODAL receptors, ALK4 and ALK7 is required for promoting differentiation of male germ cells and their entry into mitotic arrest. Finally, our data demonstrate that Nodal is specifically expressed in male germ cells and expression of the key pluripotency gene, Nanog was significantly reduced when signaling through ALK4/5/7 was blocked. Our strategy of inhibiting multiple Activin/NODAL/TGFβ receptors reduces the functional redundancy between these signaling pathways, thereby revealing new and essential roles for TGFβ and Activin signaling during testis formation and male germ cell development. PMID:23342175

  12. Inorganic material profiling using Arn+ cluster: Can we achieve high quality profiles?

    NASA Astrophysics Data System (ADS)

    Conard, T.; Fleischmann, C.; Havelund, R.; Franquet, A.; Poleunis, C.; Delcorte, A.; Vandervorst, W.

    2018-06-01

    Retrieving molecular information by sputtering of organic systems has been concretized in the last years due to the introduction of sputtering by large gas clusters which drastically eliminated the compound degradation during the analysis and has led to strong improvements in depth resolution. Rapidly however, a limitation was observed for heterogeneous systems where inorganic layers or structures needed to be profiled concurrently. As opposed to organic material, erosion of the inorganic layer appears very difficult and prone to many artefacts. To shed some light on these problems we investigated a simple system consisting of aluminum delta layer(s) buried in a silicon matrix in order to define the most favorable beam conditions for practical analysis. We show that counterintuitive to the small energy/atom used and unlike monoatomic ion sputtering, the information depth obtained with large cluster ions is typically very large (∼10 nm) and that this can be caused both by a large roughness development at early stages of the sputtering process and by a large mixing zone. As a consequence, a large deformation of the Al intensity profile is observed. Using sample rotation during profiling significantly improves the depth resolution while sample temperature has no significant effect. The determining parameter for high depth resolution still remains the total energy of the cluster instead of the energy per atom in the cluster.

  13. A nuclear F-actin scaffold stabilizes ribonucleoprotein droplets against gravity in large cells.

    PubMed

    Feric, Marina; Brangwynne, Clifford P

    2013-10-01

    The size of a typical eukaryotic cell is of the order of ∼10 μm. However, some cell types grow to very large sizes, including oocytes (immature eggs) of organisms from humans to starfish. For example, oocytes of the frog Xenopus laevis grow to a diameter ≥1 mm. They have a correspondingly large nucleus (germinal vesicle) of ∼450 μm in diameter, which is similar to smaller somatic nuclei, but contains a significantly higher concentration of actin. The form and structure of this nuclear actin remain controversial, and its potential mechanical role within these large nuclei is unknown. Here, we use a microrheology and quantitative imaging approach to show that germinal vesicles contain an elastic F-actin scaffold that mechanically stabilizes these large nuclei against gravitational forces, which are usually considered negligible within cells. We find that on actin disruption, ribonucleoprotein droplets, including nucleoli and histone locus bodies, undergo gravitational sedimentation and fusion. We develop a model that reveals how gravity becomes an increasingly potent force as cells and their nuclei grow larger than ∼10 μm, explaining the requirement for a stabilizing nuclear F-actin scaffold in large Xenopus oocytes. All life forms are subject to gravity, and our results may have broad implications for cell growth and size control.

  14. A nuclear F-actin scaffold stabilizes RNP droplets against gravity in large cells

    PubMed Central

    Feric, Marina; Brangwynne, Clifford P.

    2013-01-01

    The size of a typical eukaryotic cell is on the order of ≈10 μm. However, some cell types grow to very large sizes, including oocytes (immature eggs) of organisms from humans to starfish. For example, oocytes of the frog X. laevis grow to a diameter ≥1 mm. They contain a correspondingly large nucleus (germinal vesicle, GV) of ≈450 μm in diameter, which is similar to smaller somatic nuclei, but contains a significantly higher concentration of actin. The form and structure of this nuclear actin remain controversial, and its potential mechanical role within these large nuclei is unknown. Here, we use a microrheology and quantitative imaging approach to show that GVs contain an elastic F-actin scaffold that mechanically stabilizes these large nuclei against gravitational forces, which are usually considered negligible within cells. We find that upon actin disruption, RNA/protein droplets, including nucleoli and histone locus bodies (HLBs), undergo gravitational sedimentation and fusion. We develop a model that reveals how gravity becomes an increasingly potent force as cells and their nuclei grow larger than ≈10 μm, explaining the requirement for a stabilizing nuclear F-actin scaffold in large X. laevis ooctyes. All life forms are subject to gravity, and our results may have broad implications for cell growth and size control. PMID:23995731

  15. A Novel Nectin-mediated Cell Adhesion Apparatus That Is Implicated in Prolactin Receptor Signaling for Mammary Gland Development*

    PubMed Central

    Kitayama, Midori; Mizutani, Kiyohito; Maruoka, Masahiro; Mandai, Kenji; Sakakibara, Shotaro; Ueda, Yuki; Komori, Takahide; Shimono, Yohei; Takai, Yoshimi

    2016-01-01

    Mammary gland development is induced by the actions of various hormones to form a structure consisting of collecting ducts and milk-secreting alveoli, which comprise two types of epithelial cells known as luminal and basal cells. These cells adhere to each other by cell adhesion apparatuses whose roles in hormone-dependent mammary gland development remain largely unknown. Here we identified a novel cell adhesion apparatus at the boundary between the luminal and basal cells in addition to desmosomes. This apparatus was formed by the trans-interaction between the cell adhesion molecules nectin-4 and nectin-1, which were expressed in the luminal and basal cells, respectively. Nectin-4 of this apparatus further cis-interacted with the prolactin receptor in the luminal cells to enhance the prolactin-induced prolactin receptor signaling for alveolar development with lactogenic differentiation. Thus, a novel nectin-mediated cell adhesion apparatus regulates the prolactin receptor signaling for mammary gland development. PMID:26757815

  16. Neural Changes Underlying the Development of Episodic Memory During Middle Childhood

    PubMed Central

    Ghetti, Simona; Bunge, Silvia A.

    2012-01-01

    Episodic memory is central to the human experience. In typically developing children, episodic memory improves rapidly during middle childhood. While the developmental cognitive neuroscience of episodic memory remains largely uncharted, recent research has begun to provide important insights. It has long been assumed that hippocampus-dependent binding mechanisms are in place by early childhood, and that improvements in episodic memory observed during middle childhood result from the protracted development of the prefrontal cortex. We revisit the notion that binding mechanisms are age-invariant, and propose that changes in the hippocampus and its projections to cortical regions also contribute to the development of episodic memory. We further review the role of developmental changes in lateral prefrontal and parietal cortices in this development. Finally, we discuss changes in white matter tracts connecting brain regions that are critical for episodic memory. Overall, we argue that changes in episodic memory emerge from the concerted effort of a network of relevant brain structures. PMID:22770728

  17. Sex Chromosome Evolution, Heterochiasmy, and Physiological QTL in the Salmonid Brook Charr Salvelinus fontinalis

    PubMed Central

    Sutherland, Ben J.G.; Rico, Ciro; Audet, Céline; Bernatchez, Louis

    2017-01-01

    Whole-genome duplication (WGD) can have large impacts on genome evolution, and much remains unknown about these impacts. This includes the mechanisms of coping with a duplicated sex determination system and whether this has an impact on increasing the diversity of sex determination mechanisms. Other impacts include sexual conflict, where alleles having different optimums in each sex can result in sequestration of genes into nonrecombining sex chromosomes. Sex chromosome development itself may involve sex-specific recombination rate (i.e., heterochiasmy), which is also poorly understood. The family Salmonidae is a model system for these phenomena, having undergone autotetraploidization and subsequent rediploidization in most of the genome at the base of the lineage. The salmonid master sex determining gene is known, and many species have nonhomologous sex chromosomes, putatively due to transposition of this gene. In this study, we identify the sex chromosome of Brook Charr Salvelinus fontinalis and compare sex chromosome identities across the lineage (eight species and four genera). Although nonhomology is frequent, homologous sex chromosomes and other consistencies are present in distantly related species, indicating probable convergence on specific sex and neo-sex chromosomes. We also characterize strong heterochiasmy with 2.7-fold more crossovers in maternal than paternal haplotypes with paternal crossovers biased to chromosome ends. When considering only rediploidized chromosomes, the overall heterochiasmy trend remains, although with only 1.9-fold more recombination in the female than the male. Y chromosome crossovers are restricted to a single end of the chromosome, and this chromosome contains a large interspecific inversion, although its status between males and females remains unknown. Finally, we identify quantitative trait loci (QTL) for 21 unique growth, reproductive, and stress-related phenotypes to improve knowledge of the genetic architecture of these traits important to aquaculture and evolution. PMID:28626004

  18. Taking Action on Air Pollution Control in the Beijing-Tianjin-Hebei (BTH) Region: Progress, Challenges and Opportunities

    PubMed Central

    Wang, Li; Zhang, Fengying; Pilot, Eva; Yu, Jie; Holdaway, Jennifer; Yang, Linsheng; Li, Yonghua; Wang, Wuyi; Vardoulakis, Sotiris; Krafft, Thomas

    2018-01-01

    Due to rapid urbanization, industrialization and motorization, a large number of Chinese cities are affected by heavy air pollution. In order to explore progress, remaining challenges, and sustainability of air pollution control in the Beijing-Tianjin-Hebei (BTH) region after 2013, a mixed method analysis was undertaken. The quantitative analysis comprised an overview of air quality management in the BTH region. Semi-structured expert interviews were conducted with 12 stakeholders from various levels of government and research institutions who played substantial roles either in decision-making or in research and advising on air pollution control in the BTH region. The results indicated that with the stringent air pollution control policies, the air quality in BTH meets the targets of the Air Pollution Prevention and Control Action Plan. However, improvements vary across the region and for different pollutants. Although implementation has been decisive and was at least in parts effectively enforced, significant challenges remained with regard to industrial and traffic emission control, and national air quality limits continued to be significantly exceeded and competing development interests remained mainly unsolved. There were also concerns about the sustainability of the current air pollution control measures especially for industries due to the top-down enforcement, and the associated large burden of social cost including unemployment and social inequity resulting industrial restructuring. Better mechanisms for ensuring cross-sectoral coordination and for improved central-local government communication were suggested. Further suggestions were provided to improve the conceptual design and effective implementation of respective air pollution control strategies in BTH. Our study highlights some of the major hurdles that need to be addressed to succeed with a comprehensive air pollution control management for the Chinese mega-urban agglomerations. PMID:29425189

  19. Observations of debris flows at Chalk Cliffs, Colorado, USA: Part 1, in-situ measurements of flow dynamics, tracer particle movement and video imagery from the summer of 2009

    USGS Publications Warehouse

    McCoy, Scott W.; Coe, Jeffrey A.; Kean, Jason W.; Tucker, Greg E.; Staley, Dennis M.; Wasklewicz, Thad A.

    2011-01-01

    Debris flows initiated by surface-water runoff during short duration, moderate- to high-intensity rainfall are common in steep, rocky, and sparsely vegetated terrain. Yet large uncertainties remain about the potential for a flow to grow through entrainment of loose debris, which make formulation of accurate mechanical models of debris-flow routing difficult. Using a combination of in situ measurements of debris flow dynamics, video imagery, tracer rocks implanted with passive integrated transponders (PIT) and pre- and post-flow 2-cm resolution digital terrain models (terrain data presented in a companion paper by STALEY et alii, 2011), we investigated the entrainment and transport response of debris flows at Chalk Cliffs, CO, USA. Four monitored events during the summer of 2009 all initiated from surface-water runoff, generally less than an hour after the first measurable rain. Despite reach-scale morphology that remained relatively constant, the four flow events displayed a range of responses, from long-runout flows that entrained significant amounts of channel sediment and dammed the main-stem river, to smaller, short-runout flows that were primarily depositional in the upper basin. Tracer-rock travel-distance distributions for these events were bimodal; particles either remained immobile or they travelled the entire length of the catchment. The long-runout, large-entrainment flow differed from the other smaller flows by the following controlling factors: peak 10-minute rain intensity; duration of significant flow in the channel; and to a lesser extent, peak surge depth and velocity. Our growing database of natural debris-flow events can be used to develop linkages between observed debris-flow transport and entrainment responses and the controlling rainstorm characteristics and flow properties.

  20. Taking Action on Air Pollution Control in the Beijing-Tianjin-Hebei (BTH) Region: Progress, Challenges and Opportunities.

    PubMed

    Wang, Li; Zhang, Fengying; Pilot, Eva; Yu, Jie; Nie, Chengjing; Holdaway, Jennifer; Yang, Linsheng; Li, Yonghua; Wang, Wuyi; Vardoulakis, Sotiris; Krafft, Thomas

    2018-02-09

    Due to rapid urbanization, industrialization and motorization, a large number of Chinese cities are affected by heavy air pollution. In order to explore progress, remaining challenges, and sustainability of air pollution control in the Beijing-Tianjin-Hebei (BTH) region after 2013, a mixed method analysis was undertaken. The quantitative analysis comprised an overview of air quality management in the BTH region. Semi-structured expert interviews were conducted with 12 stakeholders from various levels of government and research institutions who played substantial roles either in decision-making or in research and advising on air pollution control in the BTH region. The results indicated that with the stringent air pollution control policies, the air quality in BTH meets the targets of the Air Pollution Prevention and Control Action Plan. However, improvements vary across the region and for different pollutants. Although implementation has been decisive and was at least in parts effectively enforced, significant challenges remained with regard to industrial and traffic emission control, and national air quality limits continued to be significantly exceeded and competing development interests remained mainly unsolved. There were also concerns about the sustainability of the current air pollution control measures especially for industries due to the top-down enforcement, and the associated large burden of social cost including unemployment and social inequity resulting industrial restructuring. Better mechanisms for ensuring cross-sectoral coordination and for improved central-local government communication were suggested. Further suggestions were provided to improve the conceptual design and effective implementation of respective air pollution control strategies in BTH. Our study highlights some of the major hurdles that need to be addressed to succeed with a comprehensive air pollution control management for the Chinese mega-urban agglomerations.

  1. Coastal Benthic Boundary Layer (CBBL) Research Program

    DTIC Science & Technology

    1998-09-01

    of gas volume and bubble size distribution on the basis of field seismo-acoustic signature remains . Indirect seismic evidence (large scale) of gas...regime was dominated by reversing tidal currents with typical speeds of 10-cm s -1 or less. Maximum bed shear stresses remained too low to resuspend or...Waals attractive force are assumed to remain unchanged for separations less than the cut-off distance, and (2) the mechanical interparticle normal force

  2. Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon.

    PubMed

    Jeon, Seong Gyu; Kayama, Hisako; Ueda, Yoshiyasu; Takahashi, Takuya; Asahara, Takashi; Tsuji, Hirokazu; Tsuji, Noriko M; Kiyono, Hiroshi; Ma, Ji Su; Kusu, Takashi; Okumura, Ryu; Hara, Hiromitsu; Yoshida, Hiroki; Yamamoto, Masahiro; Nomoto, Koji; Takeda, Kiyoshi

    2012-01-01

    Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.

  3. Vitamin and Mineral Supplements Have a Nutritionally Significant Impact on Micronutrient Intakes of Older Adults Attending Senior Centers

    USDA-ARS?s Scientific Manuscript database

    Background: Older adults frequently report use of vitamin and mineral (VM) supplements, though the impact of supplements on dietary adequacy remains largely unknown. Despite possible improvements in dietary intake, concern remains over potential excessive nutrient consumption from VM supplement us...

  4. Out of School: A Phenomenological Exploration of Extended Non-Attendance

    ERIC Educational Resources Information Center

    Baker, Matt; Bishop, Felicity L.

    2015-01-01

    The concept of "extended non-attendance" ("school phobia" or "school refusal") was distinguished from truancy early in the twentieth century, and refers to children who fear school and avoid attending. Despite much subsequent research, outcomes for those affected remain poor, and their voices remain largely absent…

  5. Microwave amplification based on quasiparticle SIS up and down frequency converters

    NASA Astrophysics Data System (ADS)

    Kojima, T.; Uzawa, Y.; Shan, W.

    2018-02-01

    Heterodyne instruments have recently attained quantum-limited low-noise performance, particularly in radio astronomy, but it is difficult to develop large heterodyne arrays such as a modern radio camera using cryogenic sensitive detectors based on microwave kinetic inductance detectors, transition edge sensors, etc. In the realization of the heterodyne array, the reduction of power dissipation for semiconductor-based amplifiers remains a major challenge. Alternatively, superconducting parametric amplifiers still seem to have several barriers to application, especially in terms of operating temperature. Here, we show a novel concept of microwave amplification based on up and down frequency-conversion processes using quasiparticle superconductor-insulator-superconductor (SIS) tunnel junctions. We demonstrate positive gain using a proof-of-concept test module, which operates with a power dissipation of several μW at a bath temperature of 4 K. The performance of the module suggests great potential for application in large arrays.

  6. Commercial expanded graphite as a low-cost, long-cycling life anode for potassium-ion batteries with conventional carbonate electrolyte

    NASA Astrophysics Data System (ADS)

    An, Yongling; Fei, Huifang; Zeng, Guifang; Ci, Lijie; Xi, Baojuan; Xiong, Shenglin; Feng, Jinkui

    2018-02-01

    Design and synthesis of capable anode materials that can store the large size K+ is the key of development for potassium-ion batteries. The low-cost and commercial expanded graphite with large particles is a graphite-derived material with good conductivity and enlarged interlayer spaces to boost the potassium ion diffusion coefficient during charge/discharge process. Thus, we achieve excellent anode performance for potassium-ion batteries based on an expanded graphite. It can deliver a capacity of 263 mAh g-1 at the rate of 10 mA g-1 and the reversible capacity remains almost unchanged after 500 cycles at a high rate of 200 mA g-1 with a coulombic efficiency of around 100%. The potassium storage mechanism is investigated by the ex situ XRD technique. This excellent potassium storage performance will make the expanded graphite promising anode candidate for potassium ion batteries.

  7. Frictional velocity-weakening in landslides on Earth and on other planetary bodies.

    PubMed

    Lucas, Antoine; Mangeney, Anne; Ampuero, Jean Paul

    2014-03-04

    One of the ultimate goals in landslide hazard assessment is to predict maximum landslide extension and velocity. Despite much work, the physical processes governing energy dissipation during these natural granular flows remain uncertain. Field observations show that large landslides travel over unexpectedly long distances, suggesting low dissipation. Numerical simulations of landslides require a small friction coefficient to reproduce the extension of their deposits. Here, based on analytical and numerical solutions for granular flows constrained by remote-sensing observations, we develop a consistent method to estimate the effective friction coefficient of landslides. This method uses a constant basal friction coefficient that reproduces the first-order landslide properties. We show that friction decreases with increasing volume or, more fundamentally, with increasing sliding velocity. Inspired by frictional weakening mechanisms thought to operate during earthquakes, we propose an empirical velocity-weakening friction law under a unifying phenomenological framework applicable to small and large landslides observed on Earth and beyond.

  8. African humid periods triggered the reactivation of a large river system in Western Sahara.

    PubMed

    Skonieczny, C; Paillou, P; Bory, A; Bayon, G; Biscara, L; Crosta, X; Eynaud, F; Malaizé, B; Revel, M; Aleman, N; Barusseau, J-P; Vernet, R; Lopez, S; Grousset, F

    2015-11-10

    The Sahara experienced several humid episodes during the late Quaternary, associated with the development of vast fluvial networks and enhanced freshwater delivery to the surrounding ocean margins. In particular, marine sediment records off Western Sahara indicate deposition of river-borne material at those times, implying sustained fluvial discharges along the West African margin. Today, however, no major river exists in this area; therefore, the origin of these sediments remains unclear. Here, using orbital radar satellite imagery, we present geomorphological data that reveal the existence of a large buried paleodrainage network on the Mauritanian coast. On the basis of evidence from the literature, we propose that reactivation of this major paleoriver during past humid periods contributed to the delivery of sediments to the Tropical Atlantic margin. This finding provides new insights for the interpretation of terrigenous sediment records off Western Africa, with important implications for our understanding of the paleohydrological history of the Sahara.

  9. Morphometric convergence between Proterozoic and post-vegetation rivers

    PubMed Central

    Ielpi, Alessandro; Rainbird, Robert H.; Ventra, Dario; Ghinassi, Massimiliano

    2017-01-01

    Proterozoic rivers flowed through barren landscapes, and lacked interactions with macroscopic organisms. It is widely held that, in the absence of vegetation, fluvial systems featured barely entrenched channels that promptly widened over floodplains during floods. This hypothesis has never been tested because of an enduring lack of Precambrian fluvial-channel morphometric data. Here we show, through remote sensing and outcrop sedimentology, that deep rivers were developed in the Proterozoic, and that morphometric parameters for large fluvial channels might have remained within a narrow range over almost 2 billion years. Our data set comprises fluvial-channel forms deposited a few tens to thousands of kilometres from their headwaters, likely the record of basin- to craton-scale systems. Large Proterozoic channel forms present width:thickness ranges matching those of Phanerozoic counterparts, suggesting closer parallels between their fluvial dynamics. This outcome may better inform analyses of extraterrestrial planetary surfaces and related comparisons with pre-vegetation Earth landscapes. PMID:28548109

  10. Locating multiple diffusion sources in time varying networks from sparse observations.

    PubMed

    Hu, Zhao-Long; Shen, Zhesi; Cao, Shinan; Podobnik, Boris; Yang, Huijie; Wang, Wen-Xu; Lai, Ying-Cheng

    2018-02-08

    Data based source localization in complex networks has a broad range of applications. Despite recent progress, locating multiple diffusion sources in time varying networks remains to be an outstanding problem. Bridging structural observability and sparse signal reconstruction theories, we develop a general framework to locate diffusion sources in time varying networks based solely on sparse data from a small set of messenger nodes. A general finding is that large degree nodes produce more valuable information than small degree nodes, a result that contrasts that for static networks. Choosing large degree nodes as the messengers, we find that sparse observations from a few such nodes are often sufficient for any number of diffusion sources to be located for a variety of model and empirical networks. Counterintuitively, sources in more rapidly varying networks can be identified more readily with fewer required messenger nodes.

  11. Adrenaline Rush: The Role of Adrenergic Receptors in Stimulant-Induced Behaviors

    PubMed Central

    Schmidt, Karl T.

    2014-01-01

    Psychostimulants, such as cocaine and amphetamines, act primarily through the monoamine neurotransmitters dopamine (DA), norepinephrine, and serotonin. Although stimulant addiction research has largely focused on DA, medication development efforts targeting the dopaminergic system have thus far been unsuccessful, leading to alternative strategies aimed at abating stimulant abuse. Noradrenergic compounds have shown promise in altering the behavioral effects of stimulants in rodents, nonhuman primates, and humans. In this review, we discuss the contribution of each adrenergic receptor (AR) subtype (α1, α2, and β) to five stimulant-induced behaviors relevant to addiction: locomotor activity, conditioned place preference, anxiety, discrimination, and self-administration. AR manipulation has diverse effects on these behaviors; each subtype profoundly influences outcomes in some paradigms but is inconsequential in others. The functional neuroanatomy and intracellular signaling mechanisms underlying the impact of AR activation/blockade on these behaviors remain largely unknown, presenting a new frontier for research on psychostimulant–AR interactions. PMID:24499709

  12. Development of an ultra-thin film comprised of a graphene membrane and carbon nanotube vein support.

    PubMed

    Lin, Xiaoyang; Liu, Peng; Wei, Yang; Li, Qunqing; Wang, Jiaping; Wu, Yang; Feng, Chen; Zhang, Lina; Fan, Shoushan; Jiang, Kaili

    2013-01-01

    Graphene, exhibiting superior mechanical, thermal, optical and electronic properties, has attracted great interest. Considering it being one-atom-thick, and the reduced mechanical strength at grain boundaries, the fabrication of large-area suspended chemical vapour deposition graphene remains a challenge. Here we report the fabrication of an ultra-thin free-standing carbon nanotube/graphene hybrid film, inspired by the vein-membrane structure found in nature. Such a square-centimetre-sized hybrid film can realize the overlaying of large-area single-layer chemical vapour deposition graphene on to a porous vein-like carbon nanotube network. The vein-membrane-like hybrid film, with graphene suspended on the carbon nanotube meshes, possesses excellent mechanical performance, optical transparency and good electrical conductivity. The ultra-thin hybrid film features an electron transparency close to 90%, which makes it an ideal gate electrode in vacuum electronics and a high-performance sample support in transmission electron microscopy.

  13. Morphometric convergence between Proterozoic and post-vegetation rivers.

    PubMed

    Ielpi, Alessandro; Rainbird, Robert H; Ventra, Dario; Ghinassi, Massimiliano

    2017-05-26

    Proterozoic rivers flowed through barren landscapes, and lacked interactions with macroscopic organisms. It is widely held that, in the absence of vegetation, fluvial systems featured barely entrenched channels that promptly widened over floodplains during floods. This hypothesis has never been tested because of an enduring lack of Precambrian fluvial-channel morphometric data. Here we show, through remote sensing and outcrop sedimentology, that deep rivers were developed in the Proterozoic, and that morphometric parameters for large fluvial channels might have remained within a narrow range over almost 2 billion years. Our data set comprises fluvial-channel forms deposited a few tens to thousands of kilometres from their headwaters, likely the record of basin- to craton-scale systems. Large Proterozoic channel forms present width:thickness ranges matching those of Phanerozoic counterparts, suggesting closer parallels between their fluvial dynamics. This outcome may better inform analyses of extraterrestrial planetary surfaces and related comparisons with pre-vegetation Earth landscapes.

  14. Adrenaline rush: the role of adrenergic receptors in stimulant-induced behaviors.

    PubMed

    Schmidt, Karl T; Weinshenker, David

    2014-04-01

    Psychostimulants, such as cocaine and amphetamines, act primarily through the monoamine neurotransmitters dopamine (DA), norepinephrine, and serotonin. Although stimulant addiction research has largely focused on DA, medication development efforts targeting the dopaminergic system have thus far been unsuccessful, leading to alternative strategies aimed at abating stimulant abuse. Noradrenergic compounds have shown promise in altering the behavioral effects of stimulants in rodents, nonhuman primates, and humans. In this review, we discuss the contribution of each adrenergic receptor (AR) subtype (α1, α2, and β) to five stimulant-induced behaviors relevant to addiction: locomotor activity, conditioned place preference, anxiety, discrimination, and self-administration. AR manipulation has diverse effects on these behaviors; each subtype profoundly influences outcomes in some paradigms but is inconsequential in others. The functional neuroanatomy and intracellular signaling mechanisms underlying the impact of AR activation/blockade on these behaviors remain largely unknown, presenting a new frontier for research on psychostimulant-AR interactions.

  15. Fabrication of large area Si cylindric drift detectors

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

    Chen, W.; Kraner, H.W.; Li, Z.

    1993-04-01

    Advanced Si drift detector, a large area cylindrical drift detector (CDD), processing steps, with the exception of the ion implantation, were carried out in the BNL class 100 cleanroom. The double-side planer process technique was developed for the fabrication of CDD. Important improvements of the double-side planer process in this fabrication are the introduction of Al implantation protection mask and the remaining of a 1000 Angstroms oxide layer in the p-window during the implantation. Another important design of the CDD is the structure called ``river,`` which ,allows the current generated on Si-SiO{sub 2} interface to ``flow`` into the guard anode,more » and thus can minimize the leakage current at the signed anode. The test result showed that most of the signal anodes have the leakage current about 0.3 nA/cm{sup 2} for the best detector.« less

  16. Surviving an epidemic -- Australian GPs on caring for people with HIV and AIDS in the early years.

    PubMed

    Newman, Christy E; Reynolds, Robert; Gray, Rebecca; Canavan, Peter; De Wit, John; McMurchie, Marilyn; McCoy, Ronald; Kidd, Michael R

    2013-10-01

    Although general practitioners (GPs) play a central role in responding to human immunodeficiency virus (HIV) in Australia, the social history of their contribution in the early years has remained largely untold. In-depth interviews were conducted with 21 GPs who provided HIV care between 1982 and 1996. De-identified transcripts were broadly coded in NVivo, then analysed for themes regarding GP experiences during the early years. Participants recalled a time of death, fear and prejudice, with large numbers of patients diagnosed with and dying from a highly stigmatised disease. An enduring emotional legacy resulted, with GPs developing survival strategies such as better managing relationships with patients, seeking mental health support and reducing working hours. These GPs represent the first generation of GPs in Australia caring for people with HIV. Understanding their experiences can inform and inspire the next generation, who inherit a much brighter future for HIV care.

  17. Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report.

    PubMed

    Vigil, Darlene; Ganta, Kavitha; Sun, Yijuan; Dorin, Richard I; Tzamaloukas, Antonios H; Servilla, Karen S

    2015-05-06

    A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus (NDI), presented with coma and hyperglycemic hyperosmolar state (HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 mOsm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with new-onset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.

  18. Pilot line report: Development of a high efficiency thin silicon solar cell

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Experimental technology advances were implemented to increase the conversion efficiency of ultrathin 2cm x 2cm cells, to demonstrate a capability for fabricating such cells at a rate of 10,000 per month, and to fabricate 200 large-area ultrathin cells to determine their feasibility of manufacture. A production rate of 10,000 50 micron m cells per month with lot average AM0 efficiencies of 11.5% was demonstrated, with peak efficiencies of 13.5% obtained. Losses in most stages of the processing were minimized, the remaining exceptions being in the photolithography and metallization steps for front contact generation and breakage handling. The 5cm x 5cm cells were fabricated with a peak yield in excess of 40% for over 10% AM0 efficiency. Greater fabrication volume is needed to fully evaluate the expected yield and efficiency levels for large cells.

  19. Small Projects Rapid Integration and Test Environment (SPRITE): Application for Increasing Robutness

    NASA Technical Reports Server (NTRS)

    Lee, Ashley; Rakoczy, John; Heather, Daniel; Sanders, Devon

    2013-01-01

    Over the past few years interest in the development and use of small satellites has rapidly gained momentum with universities, commercial, and government organizations. In a few years we may see networked clusters of dozens or even hundreds of small, cheap, easily replaceable satellites working together in place of the large, expensive and difficult-to-replace satellites now in orbit. Standards based satellite buses and deployment mechanisms, such as the CubeSat and Poly Pico-satellite Orbital Deployer (P-POD), have stimulated growth in this area. The use of small satellites is also proving to be a cost effective capability in many areas traditionally dominated by large satellites, though many challenges remain. Currently many of these small satellites undergo very little testing prior to flight. As these small satellites move from technology demonstration and student projects toward more complex operational assets, it is expected that the standards for verification and validation will increase.

  20. Visual interface for space and terrestrial analysis

    NASA Technical Reports Server (NTRS)

    Dombrowski, Edmund G.; Williams, Jason R.; George, Arthur A.; Heckathorn, Harry M.; Snyder, William A.

    1995-01-01

    The management of large geophysical and celestial data bases is now, more than ever, the most critical path to timely data analysis. With today's large volume data sets from multiple satellite missions, analysts face the task of defining useful data bases from which data and metadata (information about data) can be extracted readily in a meaningful way. Visualization, following an object-oriented design, is a fundamental method of organizing and handling data. Humans, by nature, easily accept pictorial representations of data. Therefore graphically oriented user interfaces are appealing, as long as they remain simple to produce and use. The Visual Interface for Space and Terrestrial Analysis (VISTA) system, currently under development at the Naval Research Laboratory's Backgrounds Data Center (BDC), has been designed with these goals in mind. Its graphical user interface (GUI) allows the user to perform queries, visualization, and analysis of atmospheric and celestial backgrounds data.

  1. Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report

    PubMed Central

    Vigil, Darlene; Ganta, Kavitha; Sun, Yijuan; Dorin, Richard I; Tzamaloukas, Antonios H; Servilla, Karen S

    2015-01-01

    A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus (NDI), presented with coma and hyperglycemic hyperosmolar state (HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 mOsm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with new-onset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI. PMID:25949947

  2. Facile Preparation of Porous WO3 Film for Photoelectrochemical Splitting of Natural Seawater

    NASA Astrophysics Data System (ADS)

    Shi, Yonghong; Li, Yuangang; Wei, Xiaoliang; Feng, Juan; Li, Huajing; Zhou, Wanyi

    2017-12-01

    Sunlight-driven natural seawater splitting provides a promising way for large-scale conversion and storage of solar energy. Here, we develop a facile and low-cost method via a deposition-annealing technique to fabricate porous WO3 film and demonstrate its application as a photoanode for natural seawater splitting. The WO3 film yields a photocurrent density of 1.95 mA cm-2 and possesses excellent stability at 1.23 V (versus RHE), under the illumination of 100 mW cm-2 (AM 1.5G). The photoelectrochemical performance is ascribed to the large surface area and good permeation of the electrolyte into the porous film. Furthermore, the photocurrent density remains almost the same during 3 h continuous light irradiation. The evolution of chlorine gas from seawater splitting was determined with qualitative and quantitative analyses, with a Faradic efficiency of about 56%.

  3. Characteristics and Treatments of Large Cystic Brain Metastasis: Radiosurgery and Stereotactic Aspiration

    PubMed Central

    Kim, Moinay; Cheok, Stephanie; Chung, Lawrance K.; Ung, Nolan; Thill, Kimberly; Voth, Brittany; Kwon, Do Hoon; Kim, Jeong Hoon; Kim, Chang Jin; Tenn, Stephen; Lee, Percy

    2015-01-01

    Brain metastasis represents one of the most common causes of intracranial tumors in adults, and the incidence of brain metastasis continues to rise due to the increasing survival of cancer patients. Yet, the development of cystic brain metastasis remains a relatively rare occurrence. In this review, we describe the characteristics of cystic brain metastasis and evaluate the combined use of stereotactic aspiration and radiosurgery in treating large cystic brain metastasis. The results of several studies show that stereotactic radiosurgery produces comparable local tumor control and survival rates as other surgery protocols. When the size of the tumor interferes with radiosurgery, stereotactic aspiration of the metastasis should be considered to reduce the target volume as well as decreasing the chance of radiation induced necrosis and providing symptomatic relief from mass effect. The combined use of stereotactic aspiration and radiosurgery has strong implications in improving patient outcomes. PMID:25977901

  4. Quantifying the uncertainty in heritability

    PubMed Central

    Furlotte, Nicholas A; Heckerman, David; Lippert, Christoph

    2014-01-01

    The use of mixed models to determine narrow-sense heritability and related quantities such as SNP heritability has received much recent attention. Less attention has been paid to the inherent variability in these estimates. One approach for quantifying variability in estimates of heritability is a frequentist approach, in which heritability is estimated using maximum likelihood and its variance is quantified through an asymptotic normal approximation. An alternative approach is to quantify the uncertainty in heritability through its Bayesian posterior distribution. In this paper, we develop the latter approach, make it computationally efficient and compare it to the frequentist approach. We show theoretically that, for a sufficiently large sample size and intermediate values of heritability, the two approaches provide similar results. Using the Atherosclerosis Risk in Communities cohort, we show empirically that the two approaches can give different results and that the variance/uncertainty can remain large. PMID:24670270

  5. Effective screening programmes for cervical cancer in low- and middle-income developing countries.

    PubMed

    Sankaranarayanan, R; Budukh, A M; Rajkumar, R

    2001-01-01

    Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes--either organized or opportunistic--have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and following up the targeted women. The findings from the large body of research on various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programmes and when considering new screening initiatives.

  6. Effective screening programmes for cervical cancer in low- and middle-income developing countries.

    PubMed Central

    Sankaranarayanan, R.; Budukh, A. M.; Rajkumar, R.

    2001-01-01

    Cervical cancer is an important public health problem among adult women in developing countries in South and Central America, sub-Saharan Africa, and south and south-east Asia. Frequently repeated cytology screening programmes--either organized or opportunistic--have led to a large decline in cervical cancer incidence and mortality in developed countries. In contrast, cervical cancer remains largely uncontrolled in high-risk developing countries because of ineffective or no screening. This article briefly reviews the experience from existing screening and research initiatives in developing countries. Substantial costs are involved in providing the infrastructure, manpower, consumables, follow-up and surveillance for both organized and opportunistic screening programmes for cervical cancer. Owing to their limited health care resources, developing countries cannot afford the models of frequently repeated screening of women over a wide age range that are used in developed countries. Many low-income developing countries, including most in sub-Saharan Africa, have neither the resources nor the capacity for their health services to organize and sustain any kind of screening programme. Middle-income developing countries, which currently provide inefficient screening, should reorganize their programmes in the light of experiences from other countries and lessons from their past failures. Middle-income countries intending to organize a new screening programme should start first in a limited geographical area, before considering any expansion. It is also more realistic and effective to target the screening on high-risk women once or twice in their lifetime using a highly sensitive test, with an emphasis on high coverage (>80%) of the targeted population. Efforts to organize an effective screening programme in these developing countries will have to find adequate financial resources, develop the infrastructure, train the needed manpower, and elaborate surveillance mechanisms for screening, investigating, treating, and following up the targeted women. The findings from the large body of research on various screening approaches carried out in developing countries and from the available managerial guidelines should be taken into account when reorganizing existing programmes and when considering new screening initiatives. PMID:11693978

  7. Shortfall online: The development of an educational computer game for teaching sustainable engineering to Millennial Generation students

    NASA Astrophysics Data System (ADS)

    Gennett, Zachary Andrew

    Millennial Generation students bring significant learning and teaching challenges to the classroom, because of their unique learning styles, breadth of interests related to social and environmental issues, and intimate experiences with technology. As a result, there has been an increased willingness at many universities to experiment with pedagogical strategies that depart from a traditional "learning by listening" model, and move toward more innovative methods involving active learning through computer games. In particular, current students typically express a strong interest in sustainability in which economic concerns must be weighed relative to environmental and social responsibilities. A game-based setting could prove very effective for fostering an operational understanding of these tradeoffs, and especially the social dimension which remains largely underdeveloped relative to the economic and environmental aspects. Through an examination of the educational potential of computer games, this study hypothesizes that to acquire the skills necessary to manage and understand the complexities of sustainability, Millennial Generation students must be engaged in active learning exercises that present dynamic problems and foster a high level of social interaction. This has led to the development of an educational computer game, entitled Shortfall, which simulates a business milieu for testing alternative paths regarding the principles of sustainability. This study examines the evolution of Shortfall from an educational board game that teaches the principles of environmentally benign manufacturing, to a completely networked computer game, entitled Shortfall Online that teaches the principles of sustainability. A capital-based theory of sustainability is adopted to more accurately convey the tradeoffs and opportunity costs among economic prosperity, environmental preservation, and societal responsibilities. While the economic and environmental aspects of sustainability have received considerable attention in traditional pedagogical approaches, specific focus is provided for the social dimension of sustainability, as it had remained largely underdeveloped. To measure social sustainability and provide students with an understanding of its significance, a prospective metric utilizing a social capital peer-evaluation survey, unique to Shortfall, is developed.

  8. Role of the 85-Kilobase Plasmid and Plasmid-Encoded Virulence-Associated Protein A in Intracellular Survival and Virulence of Rhodococcus equi

    PubMed Central

    Giguère, Steeve; Hondalus, Mary K.; Yager, Julie A.; Darrah, Patricia; Mosser, David M.; Prescott, John F.

    1999-01-01

    Rhodococcus equi is a facultative intracellular pathogen of macrophages and a cause of pneumonia in young horses (foals) and immunocompromised people. Isolates of R. equi from pneumonic foals typically contain large, 85- or 90-kb plasmids encoding a highly immunogenic virulence-associated protein (VapA). The objective of this study was to determine the role of the 85-kb plasmid and VapA in the intracellular survival and virulence of R. equi. Clinical isolates containing the plasmid and expressing VapA efficiently replicated within mouse macrophages in vitro, while plasmid-cured derivatives of these organisms did not multiply intracellularly. An isolate harboring the large plasmid also replicated in the tissues of experimentally infected mice, whereas its plasmid-cured derivative was rapidly cleared. All foals experimentally infected with a plasmid-containing clinical isolate developed severe bronchopneumonia, whereas the foals infected with its plasmid-cured derivative remained asymptomatic and free of visible lung lesions. By day 14 postinfection, lung bacterial burdens had increased considerably in foals challenged with the plasmid-containing clinical isolate. In contrast, bacteria could no longer be cultured from the lungs of foals challenged with the isogenic plasmid-cured derivative. A recombinant, plasmid-cured derivative expressing wild-type levels of VapA failed to replicate in macrophages and remained avirulent for both mice and foals. These results show that the 85-kb plasmid of R. equi is essential for intracellular replication within macrophages and for development of disease in the native host, the foal. However, expression of VapA alone is not sufficient to restore the virulence phenotype. PMID:10377138

  9. New Medical and Surgical Insights Into Neonatal Necrotizing Enterocolitis: A Review.

    PubMed

    Frost, Brandy L; Modi, Biren P; Jaksic, Tom; Caplan, Michael S

    2017-01-01

    Necrotizing enterocolitis (NEC) has long remained a significant cause of morbidity and mortality in neonatal intensive care units. While the mainstay of treatment for this devastating condition remains largely supportive, research efforts continue to be directed toward understanding pathophysiology as well as how best to approach surgical management when indicated. In this review, we first examine recent medical observations, including overviews on the microbiome and a brief review of the use of probiotics. Next, we discuss the use of biomarkers and how clinicians may be able to use them in the future to predict the course of disease and, perhaps, the need for surgical intervention. We then provide an overview on the use of exclusive human milk feeding and the utility of this approach in preventing NEC. Finally, we discuss recent developments in the surgical management of NEC, beginning with indications for surgery and following with a section on technical surgical considerations, including peritoneal drain vs laparotomy. The review concludes with outcomes from infants with surgically treated NEC. Although medical treatment options for NEC are largely unchanged, understanding of the disease continues to evolve. As new research methods are developed, NEC pathophysiology can be more completely understood. In time, it is hoped that data from ongoing and planned clinical trials will allow us to routinely add targeted preventive measures in addition to human milk, such as prebiotics and probiotics, to the management of high-risk infants. In addition, the discovery of novel biomarkers may not only prove useful in predicting severity of illness but also will hopefully allow for identification of the disease prior to onset of clinical signs. Finally, continued investigation into optimizing surgical outcomes is essential in this population of infants, many of whom require long-term parenteral therapy and intestinal rehabilitation.

  10. The costal skeleton of the Regourdou 1 Neandertal.

    PubMed

    Gómez-Olivencia, Asier; Holliday, Trenton; Madelaine, Stéphane; Couture-Veschambre, Christine; Maureille, Bruno

    2018-02-26

    The morphology and size of the Neandertal thorax is a subject of growing interest due to its link to general aspects of body size and shape, including physiological aspects related to bioenergetics and activity budgets. However, the number of well-preserved adult Neandertal costal remains is still low. The recent finding of new additional costal remains from the Regourdou 1 (R1) skeleton has rendered this skeleton as one of the most complete Neandertal costal skeletons with a minimum of 18 ribs represented, five of which are complete or virtually complete. Here we describe for the first time all the rib remains from R1 and compare them to a large modern Euroamerican male sample as well as to other published Neandertal individuals. The costal skeleton of this individual shows significant metric and morphological differences from our modern human male comparative sample. The perceived differences include: dorsoventrally large 1st and 2nd ribs, 3rd ribs with a very closed dorsal curvature and large maximum diameters at the posterior angle, a large tubercle-iliocostal line distance in the 4th rib, thick shafts at the dorsal end of its 6th ribs, thick mid-shafts of the 8th ribs, large articular tubercles at the 9th ribs, and thick shafts of the 11th and 12th ribs. Here we also describe a new mesosternal fragment: the left lateral half of sternebral segments 4 and 5. This portion reveals that the mesosternum of R1 had a sternal foramen in its inferiormost preserved sternal segment and supports previous estimation of the total length of this mesosternum. The new costal remains from R1 support the view that Neandertals, when compared with modern humans, show a significantly different thorax, consistent with differences found in other anatomical regions such as the vertebral column and pelvis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

    PubMed

    Lim, Lynette; Pakan, Janelle M P; Selten, Martijn M; Marques-Smith, André; Llorca, Alfredo; Bae, Sung Eun; Rochefort, Nathalie L; Marín, Oscar

    2018-06-18

    Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.

  12. Electrical coupling regulates layer 1 interneuron microcircuit formation in the neocortex

    PubMed Central

    Yao, Xing-Hua; Wang, Min; He, Xiang-Nan; He, Fei; Zhang, Shu-Qing; Lu, Wenlian; Qiu, Zi-Long; Yu, Yong-Chun

    2016-01-01

    The coexistence of electrical and chemical synapses among interneurons is essential for interneuron function in the neocortex. However, it remains largely unclear whether electrical coupling between interneurons influences chemical synapse formation and microcircuit assembly during development. Here, we show that electrical and GABAergic chemical connections robustly develop between interneurons in neocortical layer 1 over a similar time course. Electrical coupling promotes action potential generation and synchronous firing between layer 1 interneurons. Furthermore, electrically coupled interneurons exhibit strong GABA-A receptor-mediated synchronous synaptic activity. Disruption of electrical coupling leads to a loss of bidirectional, but not unidirectional, GABAergic connections. Moreover, a reduction in electrical coupling induces an increase in excitatory synaptic inputs to layer 1 interneurons. Together, these findings strongly suggest that electrical coupling between neocortical interneurons plays a critical role in regulating chemical synapse development and precise formation of circuits. PMID:27510304

  13. Major factors for facilitating change in behavioral strategies to reduce obesity

    PubMed Central

    Dalle Grave, Riccardo; Centis, Elena; Marzocchi, Rebecca; El Ghoch, Marwan; Marchesini, Giulio

    2013-01-01

    It is very unlikely that our obesity-promoting environment will change in the near future. It is therefore mandatory to improve our knowledge of the main factors associated with successful adoption of obesity-reducing behaviors. This may help design more powerful procedures and strategies to facilitate the adoption of healthy lifestyles in a “toxic” environment favoring the development of a positive energy balance. The aim of this review is to describe the main factors associated with successful adoption of obesity-reducing behaviors and to describe the most recent development, limits, and outcomes of lifestyle modification programs. The evidence regarding predictors of weight loss and weight loss maintenance remains largely incomplete. It is necessary to develop strategies matching treatments to patients’ needs to improve successful weight loss and its maintenance. How to detect and how to address these needs is a continuous, challenging, research problem. PMID:24124398

  14. Systems-Level Synthetic Biology for Advanced Biofuel Production

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

    Ruffing, Anne; Jensen, Travis J.; Strickland, Lucas Marshall

    2015-03-01

    Cyanobacteria have been shown to be capable of producing a variety of advanced biofuels; however, product yields remain well below those necessary for large scale production. New genetic tools and high throughput metabolic engineering techniques are needed to optimize cyanobacterial metabolisms for enhanced biofuel production. Towards this goal, this project advances the development of a multiple promoter replacement technique for systems-level optimization of gene expression in a model cyanobacterial host: Synechococcus sp. PCC 7002. To realize this multiple-target approach, key capabilities were developed, including a high throughput detection method for advanced biofuels, enhanced transformation efficiency, and genetic tools for Synechococcusmore » sp. PCC 7002. Moreover, several additional obstacles were identified for realization of this multiple promoter replacement technique. The techniques and tools developed in this project will help to enable future efforts in the advancement of cyanobacterial biofuels.« less

  15. Vaccines Against Malaria

    PubMed Central

    Ouattara, Amed; Laurens, Matthew B.

    2015-01-01

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

  16. Implant-retained craniofacial prostheses for facial defects

    PubMed Central

    Federspil, Philipp A.

    2012-01-01

    Craniofacial prostheses, also known as epistheses, are artificial substitutes for facial defects. The breakthrough for rehabilitation of facial defects with implant-retained prostheses came with the development of the modern silicones and bone anchorage. Following the discovery of the osseointegration of titanium in the 1950s, dental implants have been made of titanium in the 1960s. In 1977, the first extraoral titanium implant was inserted in a patient. Later, various solitary extraoral implant systems were developed. Grouped implant systems have also been developed which may be placed more reliably in areas with low bone presentation, as in the nasal and orbital region, or the ideally pneumatised mastoid process. Today, even large facial prostheses may be securely retained. The classical atraumatic surgical technique has remained an unchanged prerequisite for successful implantation of any system. This review outlines the basic principles of osseointegration as well as the main features of extraoral implantology. PMID:22073096

  17. Child development in rural China: children left behind by their migrant parents and children of nonmigrant families.

    PubMed

    Wen, Ming; Lin, Danhua

    2012-01-01

    Using recent cross-sectional data of rural children aged from 8 to 18 in Hunan Province of China, this article examines psychological, behavioral, and educational outcomes and the psychosocial contexts of these outcomes among children left behind by one or both of their rural-to-urban migrant parents compared to those living in nonmigrant families. The results showed that left-behind children were disadvantaged in health behavior and school engagement but not in perceived satisfaction. The child's psychosocial environment, captured by family socioeconomic status, socializing processes, peer and school support, and psychological traits, were associated with, to varying extent, child developmental outcomes in rural China. These influences largely remain constant for the sampled children regardless of their parents' migrant status. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

  18. Inner Speech: Development, Cognitive Functions, Phenomenology, and Neurobiology

    PubMed Central

    2015-01-01

    Inner speech—also known as covert speech or verbal thinking—has been implicated in theories of cognitive development, speech monitoring, executive function, and psychopathology. Despite a growing body of knowledge on its phenomenology, development, and function, approaches to the scientific study of inner speech have remained diffuse and largely unintegrated. This review examines prominent theoretical approaches to inner speech and methodological challenges in its study, before reviewing current evidence on inner speech in children and adults from both typical and atypical populations. We conclude by considering prospects for an integrated cognitive science of inner speech, and present a multicomponent model of the phenomenon informed by developmental, cognitive, and psycholinguistic considerations. Despite its variability among individuals and across the life span, inner speech appears to perform significant functions in human cognition, which in some cases reflect its developmental origins and its sharing of resources with other cognitive processes. PMID:26011789

  19. A proposed national strategy for tuberculosis vaccine development.

    PubMed

    Ginsberg, A M

    2000-06-01

    The global tuberculosis epidemic causes approximately 5% of deaths worldwide. Despite recent concerted and largely successful tuberculosis control efforts, the incidence of tuberculosis in the United States remains 74-fold higher than the stated elimination goal of <1 case per million population by the year 2010. Current bacille Calmette-Guérin vaccines, although efficacious in preventing extrapulmonary tuberculosis in young children, have shown widely variable efficacy in preventing adult pulmonary tuberculosis, confound skin test screening, and are not recommended for use in the United States. The Advisory Council for Elimination of Tuberculosis recently stated that tuberculosis would not be eliminated from the United States without a more effective vaccine. Recent scientific advances have created unprecedented opportunity for tuberculosis vaccine development. Therefore, members of the broad tuberculosis research and control communities have recently created and proposed a national strategy, or blueprint, for tuberculosis vaccine development, which is presented here.

  20. Developing therapeutic microRNAs for cancer

    PubMed Central

    Bader, AG; Brown, D; Stoudemire, J; Lammers, P

    2014-01-01

    Despite substantial progress in understanding the cancer-signaling network, effective therapies remain scarce due to insufficient disruption of oncogenic pathways, drug resistance and drug-induced toxicity. This complexity of cancer defines an urgent goal for researchers and clinicians to develop novel therapeutic strategies. The discovery of microRNAs (miRNAs) provides new hope for accomplishing this task. Supported by solid evidence for a critical role in cancer and bolstered by a unique mechanism of action, miRNAs are likely to yield a new class of targeted therapeutics. In contrast to current cancer medicines, miRNA-based therapies function by subtle repression of gene expression on a yet large number of oncogenic factors and are, therefore, anticipated to be highly efficacious. After the completion of target validation for several candidates, the development of therapeutic miRNAs is now moving to a new stage that involves pharmacological drug delivery, preclinical toxicology and regulatory guidelines. PMID:21633392

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