Social media and patient self-management: not all sites are created equal.
Ellis, Leonie; Showell, Chris; Turner, Paul
2013-01-01
This paper compares two social media sites that aim to support patients to enhance self-management. The first site, PatientsLikeMe is a well established global site designed to allow peer-to-peer communication between people with similar conditions. The second, HealthShare, is a recently developed site for Australians described as "Australia's Social Health Network". The comparison conducted examines the purpose, ownership, and design of both sites as well as how the data they collect is used. Analysis highlights that PatientsLikeMe actively facilitates patient self-management, while HealthShare is revealed to be a professionally moderated health information portal presented as a social networking site. While the impetus for the development of PatientsLikeMe is clear, the motives underpinning HealthShare are less obvious. With increasing patient interest in connecting with, and sharing information with one another, awareness of the nature and motivations underpinning sites that provide these services is of increasing relevance.
Zhang, Ni; Teti, Michele; Stanfield, Kellie; Campo, Shelly
2017-07-01
This exploratory qualitative study examines Chinese adolescents' health information sharing habits on social network sites. Ten focus group meetings with 76 adolescents, ages 12 to 17 years, were conducted at community-based organizations in Chicago's Chinatown. The research team transcribed the recording and analyzed the transcripts using ATLAS.ti. Chinese adolescents are using different social network sites for various topics of health information including food, physical activity, and so on. Adolescents would share useful and/or interesting health information. Many adolescents raised credibility concerns regarding health information and suggested evaluating the information based on self-experience or intuition, word-of-mouth, or information online. The findings shed lights on future intervention using social network sites to promote health among Chinese adolescents in the United States. Future interventions should provide adolescents with interesting and culturally sensitive health information and educate them to critically evaluate health information on social network sites.
Kumar, Atul; Chaugule, Viduth K; Condos, Tara E C; Barber, Kathryn R; Johnson, Clare; Toth, Rachel; Sundaramoorthy, Ramasubramanian; Knebel, Axel; Shaw, Gary S; Walden, Helen
2017-01-01
RING-BETWEENRING-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR is Parkin, mutations in which lead to early onset hereditary Parkinsonism. Parkin and other RBRs share a catalytic RBR module, but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during activation of Parkin. However, current data on active RBRs are in the absence of regulatory domains. Therefore, how individual RBRs are activated, and whether they share a common mechanism remains unclear. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces a movement in the IBR domain to reveal a cryptic ubiquitin binding site. Mutation of this site negatively impacts on Parkin’s activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, suggesting a role for interdomain association in RBR ligase mechanism. PMID:28414322
Kumar, Atul; Chaugule, Viduth K; Condos, Tara E C; Barber, Kathryn R; Johnson, Clare; Toth, Rachel; Sundaramoorthy, Ramasubramanian; Knebel, Axel; Shaw, Gary S; Walden, Helen
2017-05-01
RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms. Recent insights into Parkin regulation predict large, unknown conformational changes during Parkin activation. However, current data on active RBR ligases reflect the absence of regulatory domains. Therefore, it remains unclear how individual RBR ligases are activated, and whether they share a common mechanism. We now report the crystal structure of a human Parkin-phosphoubiquitin complex, which shows that phosphoubiquitin binding induces movement in the 'in-between RING' (IBR) domain to reveal a cryptic ubiquitin-binding site. Mutation of this site negatively affects Parkin's activity. Furthermore, ubiquitin binding promotes cooperation between Parkin molecules, which suggests a role for interdomain association in the RBR ligase mechanism.
Memo from EPA Assistant Administrator Mathy Stanislaus, regarding planning for removal and remedial activities at hardrock mining and mineral processing sites with fluid hazards, and to share the Agency’s expectations for the work that is done at these sit
Al-Attar, Ghada; De Meyer, Sara; El-Gibaly, Omaima; Michielsen, Kristien; Animosa, Lydia H; Mmari, Kristin
2017-10-01
A gender analysis was conducted to illuminate the key elements of friendships highlighted by early adolescent girls and boys in two sites for the purpose of better understanding the impact of gender norms on adolescent friendships in different contexts. Narrative interviews with early adolescents were conducted in two sites: Assiut, Egypt (n = 37) and Ghent, Belgium (n = 30). The interviews were recorded, transcribed, translated into English, and coded using Atlas.ti for analysis. In both Assiut and Ghent, early adolescents reported some similarities in defining key characteristics of their same-sex friends as well as in the activities they share. However, differences were noticed among boys and girls within each site. In addition, the scope of shared activity was broader in Ghent than in Assiut. In both sites, few opposite-sex friendships were reported. Gender norms influenced choice of friends as well as the type and place of shared activities. Building on knowledge that adolescent friendships guide and reinforce attitudes, beliefs, and behaviors that impact immediate and long-term health, our findings indicate that gender norms inform early adolescent friendships, which may impact healthy development. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Community Involvement Plan for Northeast Church Rock and Kerr-McGee Quivira Mine Sites
This Community Involvement Plan outlines opportunities for individual participation and meaningful information sharing regarding EPA’s activities in communities near Northeast Churchrock and Kerr-McGee Quivira Mine Sites.
The NIH BD2K center for big data in translational genomics
Paten, Benedict; Diekhans, Mark; Druker, Brian J; Friend, Stephen; Guinney, Justin; Gassner, Nadine; Guttman, Mitchell; James Kent, W; Mantey, Patrick; Margolin, Adam A; Massie, Matt; Novak, Adam M; Nothaft, Frank; Pachter, Lior; Patterson, David; Smuga-Otto, Maciej; Stuart, Joshua M; Van’t Veer, Laura; Haussler, David
2015-01-01
The world’s genomics data will never be stored in a single repository – rather, it will be distributed among many sites in many countries. No one site will have enough data to explain genotype to phenotype relationships in rare diseases; therefore, sites must share data. To accomplish this, the genetics community must forge common standards and protocols to make sharing and computing data among many sites a seamless activity. Through the Global Alliance for Genomics and Health, we are pioneering the development of shared application programming interfaces (APIs) to connect the world’s genome repositories. In parallel, we are developing an open source software stack (ADAM) that uses these APIs. This combination will create a cohesive genome informatics ecosystem. Using containers, we are facilitating the deployment of this software in a diverse array of environments. Through benchmarking efforts and big data driver projects, we are ensuring ADAM’s performance and utility. PMID:26174866
Information Architecture for Bilingual Web Sites.
ERIC Educational Resources Information Center
Cunliffe, Daniel; Jones, Helen; Jarvis, Melanie; Egan, Kevin; Huws, Rhian; Munro, Sian
2002-01-01
Discusses creating an information architecture for a bilingual Web site and reports work in progress on the development of a content-based bilingual Web site to facilitate shared resources between speech and language therapists. Considers a structural analysis of existing bilingual Web designs and explains a card-sorting activity conducted with…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yamamoto, Kohji, E-mail: yamamok@agr.kyushu-u.ac.jp; Suzuki, Mamoru; Higashiura, Akifumi
2013-11-01
Highlights: •Structure of Bombyx mori prostaglandin E synthase is determined. •Bound glutathione sulfonic acid is located at the glutathione-binding site. •Electron-sharing network is present in this protein. •This network includes Asn95, Asp96, and Arg98. •Site-directed mutagenesis reveals that the residues contribute to the catalytic activity. -- Abstract: Prostaglandin E synthase (PGES) catalyzes the isomerization of PGH{sub 2} to PGE{sub 2}. We previously reported the identification and structural characterization of Bombyx mori PGES (bmPGES), which belongs to Sigma-class glutathione transferase. Here, we extend these studies by determining the structure of bmPGES in complex with glutathione sulfonic acid (GTS) at a resolutionmore » of 1.37 Å using X-ray crystallography. GTS localized to the glutathione-binding site. We found that electron-sharing network of bmPGES includes Asn95, Asp96, and Arg98. Site-directed mutagenesis of these residues to create mutant forms of bmPGES mutants indicate that they contribute to catalytic activity. These results are, to our knowledge, the first to reveal the presence of an electron-sharing network in bmPGES.« less
Performance Assessment Assistance Activities in the DOE Complex - 12325
DOE Office of Scientific and Technical Information (OSTI.GOV)
Seitz, Roger R.; Phifer, Mark A.; Letourneau, Martin J.
The United States Department of Energy Office of Environmental Management (DOE-EM) has established a Performance Assessment Community of Practice (PA CoP) to foster the sharing of information among performance assessment (PA) and risk assessment practitioners, regulators and oversight personnel. The general intent is to contribute to continuous improvement in the consistency, technical adequacy and quality of implementation of PAs and risk assessments around the DOE Complex. The PA CoP activities have involved commercial disposal facilities and international participants to provide a global perspective. The PA CoP has also sponsored annual technical exchanges as a means to foster improved communication andmore » to share lessons learned from on-going modelling activities. The PA CoP encourages activities to provide programmatic and technical assistance in the form of sharing experience and lessons learned with practitioners during the development of PAs and risk assessments. This assistance complements DOE-EM reviews through the Low-Level Waste Disposal Facility Federal Review Group (LFRG) that are conducted after modelling efforts are completed. Such up-front assistance is providing additional value in terms of improving consistency and sharing of information. There has been a substantial increase in the amount of assistance being provided. The assistance has been well received by practitioners and regulators that have been involved. The paper highlights assistance and sharing of information that has been conducted in the last two years to support activities underway in support of proposed disposal facilities at Paducah, Portsmouth, and the Idaho National Laboratory and tank closure at Hanford. DOE-EM established the PA CoP to help improve the consistency and quality of implementation of modelling activities around the DOE Complex. The PA CoP has sponsored annual technical exchanges as a means to foster improved communication and to share lessons learned from ongoing modelling activities. Practitioners; project managers; oversight personnel; and regulators from United States and international facilities have participated in the three technical exchanges that have been held to date. At the working level, the PA CoP has sponsored technical assistance in support of modelling activities that are currently underway. The assistance concept provides a means to share specific experience, good practices, and lessons learned on topics of interest at a given site while the modelling is being conducted. Such up-front assistance complements the sharing of information that occurs via regular LFRG meetings and independent LFRG reviews that are conducted when the modelling effort is completed. Examples from assistance activities that have been conducted at Idaho, Paducah, Portsmouth and Hanford were highlighted in this paper. There were differences in the types of assistance provided at each site. In some cases the assistance was focused on technical support for the practitioners and management responsible for the development of the PAs. At other sites, the assistance included working with the developers and regulators/stakeholders involved in the process to help with reaching consensus on critical assumptions. Such interactions have proven to be very effective to help all parties get a chance to discuss their perspectives and better understand the different points of view. In all cases, the assistance was used as a means to share broader perspectives, experiences and lessons learned with personnel engaged in a modelling activities at a given site. The combination of technical exchanges and targeted technical assistance has provided additional means to encourage the sharing of information around the DOE Complex and globally. Feedback from practitioners, oversight personnel, regulators and stakeholders that have been involved has been overwhelmingly positive. It is believed that such sharing of information and experiences is contributing to continuous improvement in the consistency, technical adequacy, and quality of modelling activities. Although different approaches are still being used, there is an improvement in the awareness of lessons learned and implementation of practices that have proven to be effective. (authors)« less
Fostering Collaborative Learning with Mobile Web 2.0 in Semi-Formal Settings
ERIC Educational Resources Information Center
Mwanza-Simwami, Daisy
2016-01-01
Mobile Web 2.0 technologies such as: mobile apps, social networking sites and video sharing sites have become essential drivers for shaping daily activities and meeting learning needs in various settings. However, very few studies link mobile Web 2.0 to supporting collaborative learning in real-life problem solving activities in semi-formal…
Angradi, Ted R; Launspach, Jonathon J; Debbout, Rick
2018-04-01
Relative valuation of potentially affected ecosystem benefits can increase the legitimacy and social acceptance of ecosystem restoration projects. As an alternative or supplement to traditional methods of deriving beneficiary preference, we downloaded from social media and classified ≈21,000 photographs taken in two Great Lakes Areas of Concern (AOC), the St. Louis River and the Milwaukee Estuary. Our motivating presumption was that the act of taking a photograph constitutes some measure of the photographer's individual preference for, or choice of, the depicted subject matter among myriad possible subject matter. Overall, 17% of photos downloaded from the photo-sharing sites Flickr, Instagram, and Panoramio depicted an ecosystem benefit of the AOC. Percent of photographs depicting a benefit and the photographs' subject matter varied between AOCs and among photo-sharing sites. Photos shared on Instagram were less user-gender biased than other photo-sharing sites and depicted active recreation (e.g., trail use) more frequently than passive recreation (e.g., landscape viewing). Local users shared more photos depicting a benefit than non-local users. The spatial distribution of photograph locations varied between photos depicting and not depicting a benefit, and identified areas within AOCs from which few photographs were shared. As a source of beneficiary preference information, we think Instagram has some advantages over the other photo-sharing sites. When combined with other information, spatially-explicit relative valuation derived from aggregate social preference can be translated into information and knowledge useful for Great Lakes restoration decision making.
ERIC Educational Resources Information Center
Harrison, Holly
This final report describes activities and accomplishments of the Through Shared Windows (TSW) Outreach Project, a 4-year project at the University of New Mexico designed to improve services to young children with disabilities and their families. Three major outcomes were accomplished. First, a Web site was developed that focuses on observational…
YouTube Video Project: A "Cool" Way to Learn Communication Ethics
ERIC Educational Resources Information Center
Lehman, Carol M.; DuFrene, Debbie D.; Lehman, Mark W.
2010-01-01
The millennial generation embraces new technologies as a natural way of accessing and exchanging information, staying connected, and having fun. YouTube, a video-sharing site that allows users to upload, view, and share video clips, is among the latest "cool" technologies for enjoying quick laughs, employing a wide variety of corporate activities,…
Deconstructing Interaction Dynamics in Knowledge Sharing Communities
NASA Astrophysics Data System (ADS)
Aji, Ablimit; Agichtein, Eugene
Online knowledge sharing sites have recently exploded in popularity, and have began to play an important role in online information seeking. Unfortunately, many factors that influence the effectiveness of the information exchange in these communities are not well understood. This paper is an attempt to fill this gap by exploring the dynamics of information sharing in such sites - that is, identifying the factors that can explain how people respond to information requests. As a case study, we use Yahoo! Answers, one of the leading knowledge sharing portals on the web with millions of active participants. We follow the progress of thousands of questions, from posting until resolution. We examine contextual factors such as the topical area of the questions, as well as intrinsic factors of question wording, subjectivity, sentiment, and other characteristics that could influence how a community responds to an information request. Our findings could be useful for improving existing collaborative question answering systems, and for designing the next generation of knowledge sharing communities.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bradshaw, Niels; Levdikov, Vladimir M.; Zimanyi, Christina M.
PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activitymore » in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site.« less
The NIH BD2K center for big data in translational genomics.
Paten, Benedict; Diekhans, Mark; Druker, Brian J; Friend, Stephen; Guinney, Justin; Gassner, Nadine; Guttman, Mitchell; Kent, W James; Mantey, Patrick; Margolin, Adam A; Massie, Matt; Novak, Adam M; Nothaft, Frank; Pachter, Lior; Patterson, David; Smuga-Otto, Maciej; Stuart, Joshua M; Van't Veer, Laura; Wold, Barbara; Haussler, David
2015-11-01
The world's genomics data will never be stored in a single repository - rather, it will be distributed among many sites in many countries. No one site will have enough data to explain genotype to phenotype relationships in rare diseases; therefore, sites must share data. To accomplish this, the genetics community must forge common standards and protocols to make sharing and computing data among many sites a seamless activity. Through the Global Alliance for Genomics and Health, we are pioneering the development of shared application programming interfaces (APIs) to connect the world's genome repositories. In parallel, we are developing an open source software stack (ADAM) that uses these APIs. This combination will create a cohesive genome informatics ecosystem. Using containers, we are facilitating the deployment of this software in a diverse array of environments. Through benchmarking efforts and big data driver projects, we are ensuring ADAM's performance and utility. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Ward, T R; Hoang, M L; Prusty, R; Lau, C K; Keil, R L; Fangman, W L; Brewer, B J
2000-07-01
In the ribosomal DNA of Saccharomyces cerevisiae, sequences in the nontranscribed spacer 3' of the 35S ribosomal RNA gene are important to the polar arrest of replication forks at a site called the replication fork barrier (RFB) and also to the cis-acting, mitotic hyperrecombination site called HOT1. We have found that the RFB and HOT1 activity share some but not all of their essential sequences. Many of the mutations that reduce HOT1 recombination also decrease or eliminate fork arrest at one of two closely spaced RFB sites, RFB1 and RFB2. A simple model for the juxtaposition of RFB and HOT1 sequences is that the breakage of strands in replication forks arrested at RFB stimulates recombination. Contrary to this model, we show here that HOT1-stimulated recombination does not require the arrest of forks at the RFB. Therefore, while HOT1 activity is independent of replication fork arrest, HOT1 and RFB require some common sequences, suggesting the existence of a common trans-acting factor(s).
OSWER’s goal is to reduce the environmental footprint of cleanup activities at contaminated sites to the maximum extent possible. This website shares policies, tools and practices to achieve that goal across cleanup programs.
USDA-ARS?s Scientific Manuscript database
This report presents an overview of the US National Plant Germplasm System (NPGS) for an audience of plant propagators from the nursery industry, academia, and public gardens. It describes the active sites that conserve germplasm of interest to propagators and how those sites conserve their germpla...
77 FR 41801 - Solicitation for a Cooperative Agreement-Transition From Jail to the Community (TJC)
Federal Register 2010, 2011, 2012, 2013, 2014
2012-07-16
... for use by non-participating jurisdictions so that it might share with others those lessons learned... learning sites. A related objective of the implementation evaluation is to measure evidence of systems... learning sites through two primary activities: (1) Development and dissemination of tools to local...
Bradshaw, Niels; Levdikov, Vladimir M; Zimanyi, Christina M; Gaudet, Rachelle; Wilkinson, Anthony J; Losick, Richard
2017-01-01
PP2C phosphatases control biological processes including stress responses, development, and cell division in all kingdoms of life. Diverse regulatory domains adapt PP2C phosphatases to specific functions, but how these domains control phosphatase activity was unknown. We present structures representing active and inactive states of the PP2C phosphatase SpoIIE from Bacillus subtilis. Based on structural analyses and genetic and biochemical experiments, we identify an α-helical switch that shifts a carbonyl oxygen into the active site to coordinate a metal cofactor. Our analysis indicates that this switch is widely conserved among PP2C family members, serving as a platform to control phosphatase activity in response to diverse inputs. Remarkably, the switch is shared with proteasomal proteases, which we identify as evolutionary and structural relatives of PP2C phosphatases. Although these proteases use an unrelated catalytic mechanism, rotation of equivalent helices controls protease activity by movement of the equivalent carbonyl oxygen into the active site. DOI: http://dx.doi.org/10.7554/eLife.26111.001 PMID:28527238
Community Indicators: A Framework for Observing and Supporting Community Activity on Cloudworks
ERIC Educational Resources Information Center
Galley, Rebecca; Conole, Gráinne; Alevizou, Panagiota
2014-01-01
Cloudworks (Cloudworks.ac.uk) is a social networking site designed for sharing, finding and discussing learning and teaching ideas and experiences. Design and development of the site has been based on an iterative analysis, development and implementation approach, underpinned by ongoing research and evaluation. To this end, we have been seeking to…
78 FR 53765 - Agency Information Collection Activities: Proposed Collection; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-30
... patients, such as evidence-based medicine guidelines, best practice guidelines, and shared decision-making... consider a broad variety of evidence for evaluating the nature and impact of each site's interventions...
Ulissi, Zachary W.; Tang, Michael T.; Xiao, Jianping; ...
2017-07-27
Bimetallic catalysts are promising for the most difficult thermal and electrochemical reactions, but modeling the many diverse active sites on polycrystalline samples is an open challenge. Here, we present a general framework for addressing this complexity in a systematic and predictive fashion. Active sites for every stable low-index facet of a bimetallic crystal are enumerated and cataloged, yielding hundreds of possible active sites. The activity of these sites is explored in parallel using a neural-network-based surrogate model to share information between the many density functional theory (DFT) relaxations, resulting in activity estimates with an order of magnitude fewer explicit DFTmore » calculations. Sites with interesting activity were found and provide targets for follow-up calculations. This process was applied to the electrochemical reduction of CO 2 on nickel gallium bimetallics and indicated that most facets had similar activity to Ni surfaces, but a few exposed Ni sites with a very favorable on-top CO configuration. This motif emerged naturally from the predictive modeling and represents a class of intermetallic CO 2 reduction catalysts. These sites rationalize recent experimental reports of nickel gallium activity and why previous materials screens missed this exciting material. Most importantly these methods suggest that bimetallic catalysts will be discovered by studying facet reactivity and diversity of active sites more systematically.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ulissi, Zachary W.; Tang, Michael T.; Xiao, Jianping
Bimetallic catalysts are promising for the most difficult thermal and electrochemical reactions, but modeling the many diverse active sites on polycrystalline samples is an open challenge. Here, we present a general framework for addressing this complexity in a systematic and predictive fashion. Active sites for every stable low-index facet of a bimetallic crystal are enumerated and cataloged, yielding hundreds of possible active sites. The activity of these sites is explored in parallel using a neural-network-based surrogate model to share information between the many density functional theory (DFT) relaxations, resulting in activity estimates with an order of magnitude fewer explicit DFTmore » calculations. Sites with interesting activity were found and provide targets for follow-up calculations. This process was applied to the electrochemical reduction of CO 2 on nickel gallium bimetallics and indicated that most facets had similar activity to Ni surfaces, but a few exposed Ni sites with a very favorable on-top CO configuration. This motif emerged naturally from the predictive modeling and represents a class of intermetallic CO 2 reduction catalysts. These sites rationalize recent experimental reports of nickel gallium activity and why previous materials screens missed this exciting material. Most importantly these methods suggest that bimetallic catalysts will be discovered by studying facet reactivity and diversity of active sites more systematically.« less
NASA Astrophysics Data System (ADS)
Pordes, Ruth; OSG Consortium; Petravick, Don; Kramer, Bill; Olson, Doug; Livny, Miron; Roy, Alain; Avery, Paul; Blackburn, Kent; Wenaus, Torre; Würthwein, Frank; Foster, Ian; Gardner, Rob; Wilde, Mike; Blatecky, Alan; McGee, John; Quick, Rob
2007-07-01
The Open Science Grid (OSG) provides a distributed facility where the Consortium members provide guaranteed and opportunistic access to shared computing and storage resources. OSG provides support for and evolution of the infrastructure through activities that cover operations, security, software, troubleshooting, addition of new capabilities, and support for existing and engagement with new communities. The OSG SciDAC-2 project provides specific activities to manage and evolve the distributed infrastructure and support it's use. The innovative aspects of the project are the maintenance and performance of a collaborative (shared & common) petascale national facility over tens of autonomous computing sites, for many hundreds of users, transferring terabytes of data a day, executing tens of thousands of jobs a day, and providing robust and usable resources for scientific groups of all types and sizes. More information can be found at the OSG web site: www.opensciencegrid.org.
2013-01-01
Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription) family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM), which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors. PMID:23324445
Implementing a user-driven online quality improvement toolkit for cancer care.
Luck, Jeff; York, Laura S; Bowman, Candice; Gale, Randall C; Smith, Nina; Asch, Steven M
2015-05-01
Peer-to-peer collaboration within integrated health systems requires a mechanism for sharing quality improvement lessons. The Veterans Health Administration (VA) developed online compendia of tools linked to specific cancer quality indicators. We evaluated awareness and use of the toolkits, variation across facilities, impact of social marketing, and factors influencing toolkit use. A diffusion of innovations conceptual framework guided the collection of user activity data from the Toolkit Series SharePoint site and an online survey of potential Lung Cancer Care Toolkit users. The VA Toolkit Series site had 5,088 unique visitors in its first 22 months; 5% of users accounted for 40% of page views. Social marketing communications were correlated with site usage. Of survey respondents (n = 355), 54% had visited the site, of whom 24% downloaded at least one tool. Respondents' awareness of the lung cancer quality performance of their facility, and facility participation in quality improvement collaboratives, were positively associated with Toolkit Series site use. Facility-level lung cancer tool implementation varied widely across tool types. The VA Toolkit Series achieved widespread use and a high degree of user engagement, although use varied widely across facilities. The most active users were aware of and active in cancer care quality improvement. Toolkit use seemed to be reinforced by other quality improvement activities. A combination of user-driven tool creation and centralized toolkit development seemed to be effective for leveraging health information technology to spread disease-specific quality improvement tools within an integrated health care system. Copyright © 2015 by American Society of Clinical Oncology.
Enabling Interoperable and Selective Data Sharing among Social Networking Sites
NASA Astrophysics Data System (ADS)
Shin, Dongwan; Lopes, Rodrigo
With the widespread use of social networking (SN) sites and even introduction of a social component in non-social oriented services, there is a growing concern over user privacy in general, how to handle and share user profiles across SN sites in particular. Although there have been several proprietary or open source-based approaches to unifying the creation of third party applications, the availability and retrieval of user profile information are still limited to the site where the third party application is run, mostly devoid of the support for data interoperability. In this paper we propose an approach to enabling interopearable and selective data sharing among SN sites. To support selective data sharing, we discuss an authenticated dictionary (ADT)-based credential which enables a user to share only a subset of her information certified by external SN sites with applications running on an SN site. For interoperable data sharing, we propose an extension to the OpenSocial API so that it can provide an open source-based framework for allowing the ADT-based credential to be used seamlessly among different SN sites.
Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase.
Fenwick, Michael K; Mehta, Angad P; Zhang, Yang; Abdelwahed, Sameh H; Begley, Tadhg P; Ealick, Steven E
2015-03-27
Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active site metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.
Catalytically active Au-O(OH) x- species stabilized by alkali ions on zeolites and mesoporous oxides
Yang, Ming; Li, Sha; Wang, Yuan; ...
2014-11-27
Here we report that the addition of alkali ions (sodium or potassium) to gold on KLTL-zeolite and mesoporous MCM-41 silica stabilizes mononuclear gold in Au-O(OH) x-(Na or K) ensembles. This single-site gold species is active for the low-temperature (<200°C) water-gas shift (WGS) reaction. Unexpectedly, gold is thus similar to platinum in creating –O linkages with more than eight alkali ions and establishing an active site on various supports. The intrinsic activity of the single-site gold species is the same on irreducible supports as on reducible ceria, iron oxide, and titania supports, apparently all sharing a common, similarly structured gold activemore » site. This finding paves the way for using earth-abundant supports to disperse and stabilize precious metal atoms with alkali additives for the WGS and potentially other fuel-processing reactions.« less
Nicotinamide Cofactors Suppress Active-Site Labeling of Aldehyde Dehydrogenases.
Stiti, Naim; Chandrasekar, Balakumaran; Strubl, Laura; Mohammed, Shabaz; Bartels, Dorothea; van der Hoorn, Renier A L
2016-06-17
Active site labeling by (re)activity-based probes is a powerful chemical proteomic tool to globally map active sites in native proteomes without using substrates. Active site labeling is usually taken as a readout for the active state of the enzyme because labeling reflects the availability and reactivity of active sites, which are hallmarks for enzyme activities. Here, we show that this relationship holds tightly, but we also reveal an important exception to this rule. Labeling of Arabidopsis ALDH3H1 with a chloroacetamide probe occurs at the catalytic Cys, and labeling is suppressed upon nitrosylation and oxidation, and upon treatment with other Cys modifiers. These experiments display a consistent and strong correlation between active site labeling and enzymatic activity. Surprisingly, however, labeling is suppressed by the cofactor NAD(+), and this property is shared with other members of the ALDH superfamily and also detected for unrelated GAPDH enzymes with an unrelated hydantoin-based probe in crude extracts of plant cell cultures. Suppression requires cofactor binding to its binding pocket. Labeling is also suppressed by ALDH modulators that bind at the substrate entrance tunnel, confirming that labeling occurs through the substrate-binding cavity. Our data indicate that cofactor binding adjusts the catalytic Cys into a conformation that reduces the reactivity toward chloroacetamide probes.
Social Networking Adapted for Distributed Scientific Collaboration
NASA Technical Reports Server (NTRS)
Karimabadi, Homa
2012-01-01
Share is a social networking site with novel, specially designed feature sets to enable simultaneous remote collaboration and sharing of large data sets among scientists. The site will include not only the standard features found on popular consumer-oriented social networking sites such as Facebook and Myspace, but also a number of powerful tools to extend its functionality to a science collaboration site. A Virtual Observatory is a promising technology for making data accessible from various missions and instruments through a Web browser. Sci-Share augments services provided by Virtual Observatories by enabling distributed collaboration and sharing of downloaded and/or processed data among scientists. This will, in turn, increase science returns from NASA missions. Sci-Share also enables better utilization of NASA s high-performance computing resources by providing an easy and central mechanism to access and share large files on users space or those saved on mass storage. The most common means of remote scientific collaboration today remains the trio of e-mail for electronic communication, FTP for file sharing, and personalized Web sites for dissemination of papers and research results. Each of these tools has well-known limitations. Sci-Share transforms the social networking paradigm into a scientific collaboration environment by offering powerful tools for cooperative discourse and digital content sharing. Sci-Share differentiates itself by serving as an online repository for users digital content with the following unique features: a) Sharing of any file type, any size, from anywhere; b) Creation of projects and groups for controlled sharing; c) Module for sharing files on HPC (High Performance Computing) sites; d) Universal accessibility of staged files as embedded links on other sites (e.g. Facebook) and tools (e.g. e-mail); e) Drag-and-drop transfer of large files, replacing awkward e-mail attachments (and file size limitations); f) Enterprise-level data and messaging encryption; and g) Easy-to-use intuitive workflow.
Get Involved in Planetary Discoveries through New Worlds, New Discoveries
NASA Astrophysics Data System (ADS)
Shupla, Christine; Shipp, S. S.; Halligan, E.; Dalton, H.; Boonstra, D.; Buxner, S.; SMD Planetary Forum, NASA
2013-01-01
"New Worlds, New Discoveries" is a synthesis of NASA’s 50-year exploration history which provides an integrated picture of our new understanding of our solar system. As NASA spacecraft head to and arrive at key locations in our solar system, "New Worlds, New Discoveries" provides an integrated picture of our new understanding of the solar system to educators and the general public! The site combines the amazing discoveries of past NASA planetary missions with the most recent findings of ongoing missions, and connects them to the related planetary science topics. "New Worlds, New Discoveries," which includes the "Year of the Solar System" and the ongoing celebration of the "50 Years of Exploration," includes 20 topics that share thematic solar system educational resources and activities, tied to the national science standards. This online site and ongoing event offers numerous opportunities for the science community - including researchers and education and public outreach professionals - to raise awareness, build excitement, and make connections with educators, students, and the public about planetary science. Visitors to the site will find valuable hands-on science activities, resources and educational materials, as well as the latest news, to engage audiences in planetary science topics and their related mission discoveries. The topics are tied to the big questions of planetary science: how did the Sun’s family of planets and bodies originate and how have they evolved? How did life begin and evolve on Earth, and has it evolved elsewhere in our solar system? Scientists and educators are encouraged to get involved either directly or by sharing "New Worlds, New Discoveries" and its resources with educators, by conducting presentations and events, sharing their resources and events to add to the site, and adding their own public events to the site’s event calendar! Visit
Tong, Pin; Monahan, Jack; Prendergast, James G D
2017-03-01
Large-scale gene expression datasets are providing an increasing understanding of the location of cis-eQTLs in the human genome and their role in disease. However, little is currently known regarding the extent of regulatory site-sharing between genes. This is despite it having potentially wide-ranging implications, from the determination of the way in which genetic variants may shape multiple phenotypes to the understanding of the evolution of human gene order. By first identifying the location of non-redundant cis-eQTLs, we show that regulatory site-sharing is a relatively common phenomenon in the human genome, with over 10% of non-redundant regulatory variants linked to the expression of multiple nearby genes. We show that these shared, local regulatory sites are linked to high levels of chromatin looping between the regulatory sites and their associated genes. In addition, these co-regulated gene modules are found to be strongly conserved across mammalian species, suggesting that shared regulatory sites have played an important role in shaping human gene order. The association of these shared cis-eQTLs with multiple genes means they also appear to be unusually important in understanding the genetics of human phenotypes and pleiotropy, with shared regulatory sites more often linked to multiple human phenotypes than other regulatory variants. This study shows that regulatory site-sharing is likely an underappreciated aspect of gene regulation and has important implications for the understanding of various biological phenomena, including how the two and three dimensional structures of the genome have been shaped and the potential causes of disease pleiotropy outside coding regions.
Frederick, Thomas E; Peng, Jeffrey W
2018-01-01
Increasing evidence shows that active sites of proteins have non-trivial conformational dynamics. These dynamics include active site residues sampling different local conformations that allow for multiple, and possibly novel, inhibitor binding poses. Yet, active site dynamics garner only marginal attention in most inhibitor design efforts and exert little influence on synthesis strategies. This is partly because synthesis requires a level of atomic structural detail that is frequently missing in current characterizations of conformational dynamics. In particular, while the identity of the mobile protein residues may be clear, the specific conformations they sample remain obscure. Here, we show how an appropriate choice of ligand can significantly sharpen our abilities to describe the interconverting binding poses (conformations) of protein active sites. Specifically, we show how 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid (CBAP) exposes otherwise hidden dynamics of a protein active site that binds β-lactam antibiotics. When CBAP acylates (binds) the active site serine of the β-lactam sensor domain of BlaR1 (BlaRS), it shifts the time scale of the active site dynamics to the slow exchange regime. Slow exchange enables direct characterization of inter-converting protein and bound ligand conformations using NMR methods. These methods include chemical shift analysis, 2-d exchange spectroscopy, off-resonance ROESY of the bound ligand, and reduced spectral density mapping. The active site architecture of BlaRS is shared by many β-lactamases of therapeutic interest, suggesting CBAP could expose functional motions in other β-lactam binding proteins. More broadly, CBAP highlights the utility of identifying chemical probes common to structurally homologous proteins to better expose functional motions of active sites.
Active Site Sharing and Subterminal Hairpin Recognition in a New Class of DNA Transposases
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ronning, Donald R.; Guynet, Catherine; Ton-Hoang, Bao
2010-07-20
Many bacteria harbor simple transposable elements termed insertion sequences (IS). In Helicobacter pylori, the chimeric IS605 family elements are particularly interesting due to their proximity to genes encoding gastric epithelial invasion factors. Protein sequences of IS605 transposases do not bear the hallmarks of other well-characterized transposases. We have solved the crystal structure of full-length transposase (TnpA) of a representative member, ISHp608. Structurally, TnpA does not resemble any characterized transposase; rather, it is related to rolling circle replication (RCR) proteins. Consistent with RCR, Mg{sup 2+} and a conserved tyrosine, Tyr127, are essential for DNA nicking and the formation of a covalentmore » intermediate between TnpA and DNA. TnpA is dimeric, contains two shared active sites, and binds two DNA stem loops representing the conserved inverted repeats near each end of ISHp608. The cocrystal structure with stem-loop DNA illustrates how this family of transposases specifically recognizes and pairs ends, necessary steps during transposition.« less
Discovery and characterization of a new family of lytic polysaccharide monooxygenases.
Hemsworth, Glyn R; Henrissat, Bernard; Davies, Gideon J; Walton, Paul H
2014-02-01
Lytic polysaccharide monooxygenases (LPMOs) are a recently discovered class of enzymes capable of oxidizing recalcitrant polysaccharides. They are attracting considerable attention owing to their potential use in biomass conversion, notably in the production of biofuels. Previous studies have identified two discrete sequence-based families of these enzymes termed AA9 (formerly GH61) and AA10 (formerly CBM33). Here, we report the discovery of a third family of LPMOs. Using a chitin-degrading exemplar from Aspergillus oryzae, we show that the three-dimensional structure of the enzyme shares some features of the previous two classes of LPMOs, including a copper active center featuring the 'histidine brace' active site, but is distinct in terms of its active site details and its EPR spectroscopy. The newly characterized AA11 family expands the LPMO clan, potentially broadening both the range of potential substrates and the types of reactive copper-oxygen species formed at the active site of LPMOs.
Shared virtual environments for aerospace training
NASA Technical Reports Server (NTRS)
Loftin, R. Bowen; Voss, Mark
1994-01-01
Virtual environments have the potential to significantly enhance the training of NASA astronauts and ground-based personnel for a variety of activities. A critical requirement is the need to share virtual environments, in real or near real time, between remote sites. It has been hypothesized that the training of international astronaut crews could be done more cheaply and effectively by utilizing such shared virtual environments in the early stages of mission preparation. The Software Technology Branch at NASA's Johnson Space Center has developed the capability for multiple users to simultaneously share the same virtual environment. Each user generates the graphics needed to create the virtual environment. All changes of object position and state are communicated to all users so that each virtual environment maintains its 'currency.' Examples of these shared environments will be discussed and plans for the utilization of the Department of Defense's Distributed Interactive Simulation (DIS) protocols for shared virtual environments will be presented. Finally, the impact of this technology on training and education in general will be explored.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stoddard, Ethan G.; Killinger, Bryan J.; Nair, Reji N.
Glutathione S-transferases (GSTs) comprise a highly diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione to various endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured by colorimetric assays, measurement of the individual contribution from specific isoforms and their contribution to the detoxification of xenobiotics in complex biological samples has not been possible. For this reason, we have developed two activity-based probes that characterize active glutathione transferases in mammalian tissues. The GST active site is comprised of a glutathione binding “G site” and a distinct substrate binding “Hmore » site”. Therefore, we developed (1) a glutathione-based photoaffinity probe (GSH-ABP) to target the “G site”, and (2) a probe designed to mimic a substrate molecule and show “H site” activity (GST-ABP). The GSH-ABP features a photoreactive moiety for UV-induced covalent binding to GSTs and glutathione-binding enzymes. The GST-ABP is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competitors in liver homogenates. Herein, we present robust tools for the novel characterization of enzyme- and active site-specific GST activity in mammalian model systems.« less
ERIC Educational Resources Information Center
Garcia, Leandro Sumida; Silva, Camila Mariane Costa
2016-01-01
Social media technologies were introduced among the modern society and are part of its routine in many ways--knowledge acquisition and sharing, interpersonal relationships, media diffusion--sometimes complementing and even substituting tools that were specifically designed for similar activities. This research compares social media sites and…
Collaboration Creation: Lessons Learned from Establishing an Online Professional Learning Community
ERIC Educational Resources Information Center
Gray, Colin; Smyth, Keith
2012-01-01
This paper describes the design, implementation, evaluation and further refinement of an ELGG-based social networking site to support professional development activity, project group and special interest groups, and the discussion and sharing of educational experiences and resources across Edinburgh Napier University in the United Kingdom.…
ADP Regulates SNF1, the Saccharomyces cerevisiae Homolog of AMP-Activated Protein Kinase
Mayer, Faith V.; Heath, Richard; Underwood, Elizabeth; Sanders, Matthew J.; Carmena, David; McCartney, Rhonda R.; Leiper, Fiona C.; Xiao, Bing; Jing, Chun; Walker, Philip A.; Haire, Lesley F.; Ogrodowicz, Roksana; Martin, Stephen R.; Schmidt, Martin C.; Gamblin, Steven J.; Carling, David
2011-01-01
Summary The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK. PMID:22019086
Sharing of Alcohol-Related Content on Social Networking Sites: Frequency, Content, and Correlates.
Erevik, Eilin K; Torsheim, Torbjørn; Vedaa, Øystein; Andreassen, Cecilie S; Pallesen, Ståle
2017-05-01
The present study aimed to explore students' reports of their sharing of alcohol-related content on different social networking sites (i.e., frequency of sharing and connotations of alcohol-related posts), and to identify indicators of such posting. Students at the four largest institutions for higher education in Bergen, Norway, were invited to participate in an Internet-based survey. The sample size was 11,236 (a 39.4% response rate). The survey included questions about disclosure of alcohol-related content on social networking sites, alcohol use (using the Alcohol Use Disorders Identification Test), personality factors (using the Mini-IPIP), and demographic characteristics. Binary logistic regressions were used to analyze indicators of frequent sharing of alcohol-related content depicting positive and negative aspects of alcohol use. A majority of the students had posted alcohol-related content (71.0%), although few reported having done so frequently. Positive aspects of alcohol use (e.g., enjoyment or social community) were most frequently shared. Young, single, and extroverted students with high alcohol consumption were more likely to report frequent sharing of alcohol-related content. Positive attitudes toward posting alcohol-related content and reports of exposure to such content particularly increased the likelihood of one's own posting of alcohol-related content. Positive aspects of alcohol use seem to be emphasized on social networking sites. Sharing of alcohol-related content is associated with heightened alcohol use, which implies that such sites can be relevant for prevention agents. Social influence from social networking sites, such as exposure to others' alcohol-related content, is associated with one's own sharing of similar content.
NASA Astrophysics Data System (ADS)
Mac Dougall, Jean S.; Mc Leod, Roger D.; Mc Leod, David M.
2003-10-01
Florida purchased the Tequesta ([Langue] doc Christ Spirit-signal) Indian site along the Miami River site that vigorously pulsates with even minor rainstorms entering or leaving the area. Although there is a laughable chimera of a fountain of youth associated with Ponce de Leons discovery of the Florida peninsula in about AD 1513, the Calusa (Royal Christ Jesus Spirit-signal) Indian Nation has an associated significance with EMF signals they possibly monitored throughout their area of activity. Our efforts have also led to the investigation of cultural and other influences implied by the Matacumbe Keys that indicate a shared commonality of awareness with Native Americans of the northeast such as Metacomet, or regions like Maines Grand Lake Matagamon and its associated electromagnetic Spirit Signal. Wikiwa Springs near Orlando shares much with Massachusetts (adherent of serpent Jesus Christ Spirit-signal) Natick, and New Hampshires Naticook Island. These are the locales of environmentally sensitive instrumentation.
A search for structurally similar cellular internal ribosome entry sites
Baird, Stephen D.; Lewis, Stephen M.; Turcotte, Marcel; Holcik, Martin
2007-01-01
Internal ribosome entry sites (IRES) allow ribosomes to be recruited to mRNA in a cap-independent manner. Some viruses that impair cap-dependent translation initiation utilize IRES to ensure that the viral RNA will efficiently compete for the translation machinery. IRES are also employed for the translation of a subset of cellular messages during conditions that inhibit cap-dependent translation initiation. IRES from viruses like Hepatitis C and Classical Swine Fever virus share a similar structure/function without sharing primary sequence similarity. Of the cellular IRES structures derived so far, none were shown to share an overall structural similarity. Therefore, we undertook a genome-wide search of human 5′UTRs (untranslated regions) with an empirically derived structure of the IRES from the key inhibitor of apoptosis, X-linked inhibitor of apoptosis protein (XIAP), to identify novel IRES that share structure/function similarity. Three of the top matches identified by this search that exhibit IRES activity are the 5′UTRs of Aquaporin 4, ELG1 and NF-kappaB repressing factor (NRF). The structures of AQP4 and ELG1 IRES have limited similarity to the XIAP IRES; however, they share trans-acting factors that bind the XIAP IRES. We therefore propose that cellular IRES are not defined by overall structure, as viral IRES, but are instead dependent upon short motifs and trans-acting factors for their function. PMID:17591613
NASA Technical Reports Server (NTRS)
Ward, Robin A.
2002-01-01
The primary goal of this project was to continue populating the currently existing web site developed in 1998 in conjunction with the NASA Dryden Flight Research Center and California Polytechnic State University, with more mathematics lesson plans and activities that K-12 teachers, students, home-schoolers, and parents could access. All of the activities, while demonstrating some mathematical topic, also showcase the research endeavors of the NASA Dryden Flight Research Center. The website is located at: http://daniel.calpoly.edu/dfrc/Robin. The secondary goal of this project was to share the web-based activities with educators at various conferences and workshops. To address the primary goal of this project, over the past year, several new activities were posted on the web site and some of the existing activities were enhanced to contain more video clips, photos, and materials for teachers. To address the project's secondary goal, the web-based activities were showcased at several conferences and workshops. Additionally, in order to measure and assess the outreach impact of the web site, a link to the web site hitbox.com was established in April 2001, which allowed for the collection of traffic statistics against the web site (such as the domains of visitors, the frequency of visitors to this web site, etc.) Provided is a description of some of the newly created activities posted on the web site during the project period of 2001-2002, followed by a description of the conferences and workshops at which some of the web-based activities were showcased. Next is a brief summary of the web site's traffic statistics demonstrating its worldwide educational impact, followed by a listing of some of the awards and accolades the web site has received.
ERIC Educational Resources Information Center
Zembylas, Michalinos
2012-01-01
The present essay discusses the value of citizenship as shared fate in sites of ethnic conflict and analyzes its implications for citizenship education in light of three issues: first, the requirements of affective relationality in the notion of citizenship-as-shared fate; second, the tensions between the values of human rights and shared fate in…
Holloway, Lawrence E.; Qu, Zhihua; Mohr-Schroeder, Margaret J.; ...
2017-02-06
In this study, we consider collaborative power systems education through the FEEDER consortium. To increase students' access to power engineering educational content, the consortium of seven universities was formed. A framework is presented to characterize different collaborative education activities among the universities. Three of these approaches of collaborative educational activities are presented and discussed. These include 1) cross-institutional blended courses ("MS-MD''); 2) cross-institutional distance courses ("SS-MD''); and 3) single-site special experiential courses and concentrated on-site programs available to students across consortium institutions ("MS-SD''). As a result, this paper presents the advantages and disadvantages of each approach.
ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism.
Parke, Courtney L; Wojcik, Edward J; Kim, Sunyoung; Worthylake, David K
2010-02-19
Motor proteins couple steps in ATP binding and hydrolysis to conformational switching both in and remote from the active site. In our kinesin.AMPPPNP crystal structure, closure of the active site results in structural transformations appropriate for microtubule binding and organizes an orthosteric two-water cluster. We conclude that a proton is shared between the lytic water, positioned for gamma-phosphate attack, and a second water that serves as a general base. To our knowledge, this is the first experimental detection of the catalytic base for any ATPase. Deprotonation of the second water by switch residues likely triggers subsequent large scale structural rearrangements. Therefore, the catalytic base is responsible for initiating nucleophilic attack of ATP and for relaying the positive charge over long distances to initiate mechanotransduction. Coordination of switch movements via sequential proton transfer along paired water clusters may be universal for nucleotide triphosphatases with conserved active sites, such as myosins and G-proteins.
Inhalational anaesthetics and n-alcohols share a site of action in the neuronal Shaw2 Kv channel
Bhattacharji, Aditya; Klett, Nathan; Go, Ramon Christopher V; Covarrubias, Manuel
2010-01-01
Background and purpose: Neuronal ion channels are key targets of general anaesthetics and alcohol, and binding of these drugs to pre-existing and relatively specific sites is thought to alter channel gating. However, the underlying molecular mechanisms of this action are still poorly understood. Here, we investigated the neuronal Shaw2 voltage-gated K+ (Kv) channel to ask whether the inhalational anaesthetic halothane and n-alcohols share a binding site near the activation gate of the channel. Experimental approach: Focusing on activation gate mutations that affect channel modulation by n-alcohols, we investigated n-alcohol-sensitive and n-alcohol-resistant Kv channels heterologously expressed in Xenopus oocytes to probe the functional modulation by externally applied halothane using two-electrode voltage clamping and a gas-tight perfusion system. Key results: Shaw2 Kv channels are reversibly inhibited by halothane in a dose-dependent and saturable manner (K0.5= 400 µM; nH= 1.2). Also, discrete mutations in the channel's S4S5 linker are sufficient to reduce or confer inhibition by halothane (Shaw2-T330L and Kv3.4-G371I/T378A respectively). Furthermore, a point mutation in the S6 segment of Shaw2 (P410A) converted the halothane-induced inhibition into halothane-induced potentiation. Lastly, the inhibition resulting from the co-application of n-butanol and halothane is consistent with the presence of overlapping binding sites for these drugs and weak binding cooperativity. Conclusions and implications: These observations strongly support a molecular model of a general anaesthetic binding site in the Shaw2 Kv channel. This site may involve the amphiphilic interface between the S4S5 linker and the S6 segment, which plays a pivotal role in Kv channel activation. PMID:20136839
Jabbour, Joe; Dhillon, Haryana M; Shepherd, Heather L; Sundaresan, Puma; Milross, Chris; Clark, Jonathan R
2018-05-28
Is there a relationship between decision-making preferences and psychological distress? Patients who had received treatment for head and neck cancer (HNC) at four institutions within NSW, Australia were invited to complete a single questionnaire. Five hundred and ninety-seven patients completed the questionnaire. The majority of patients (308, 54%) preferred shared decision making. Significant predictors of a preference towards active decision making were education level (OR 2.1 for tertiary, p < 0.001), primary cancer site (OR 1.9 for thyroid compared to salivary gland, p = 0.024) and gender (OR 1.4 for female, p = 0.028). Mean psychological distress score on Kessler 6 (K6) was 9 (Range: 0-28). Significant predictors of psychological distress were age (p < 0.001), gender (p < 0.001), primary site (p < 0.01), and decision preference (p < 0.01). HNC patients who are either tertiary educated or female are more likely to prefer active involvement in decision-making. Psychological distress is more likely in patients actively involved in decision making, younger patients, and in females. Patients experienced paternalistic decision-making, but most preferred active or a shared approached. Clinicians need to be aware of potential for psychological distress in active decision-makers and refer patients for psychosocial support. Copyright © 2018. Published by Elsevier B.V.
Constructing Glocal Identities through Multilingual Writing Practices on Flickr.com[R
ERIC Educational Resources Information Center
Lee, Carmen K. M.; Barton, David
2011-01-01
This article reports on a study of user-generated multilingual writing activities on the photo sharing site, Flickr.com[R]. It discusses how Flickr users deploy their multilingual resources when interacting with international audiences, the factors affecting their language choice, and how new multilingual identities are constructed. An exploratory…
Who Defines "Democratic Leadership?": Three High School Principals Respond to Site-Based Reforms.
ERIC Educational Resources Information Center
Brouillette, Liane
1997-01-01
Focuses on behaviors and activities of three high school principals as they respond to district's decision to implement a shared decision-making model designed to give teachers and parents a larger voice. Describes these administrators' varying responses, along with varied ways democratic leadership was multilaterally defined in each school by…
Bomati, Erin K.; Noel, Joseph P.
2005-01-01
We describe the three-dimensional structure of sinapyl alcohol dehydrogenase (SAD) from Populus tremuloides (aspen), a member of the NADP(H)-dependent dehydrogenase family that catalyzes the last reductive step in the formation of monolignols. The active site topology revealed by the crystal structure substantiates kinetic results indicating that SAD maintains highest specificity for the substrate sinapaldehyde. We also report substantial substrate inhibition kinetics for the SAD-catalyzed reduction of hydroxycinnamaldehydes. Although SAD and classical cinnamyl alcohol dehydrogenases (CADs) catalyze the same reaction and share some sequence identity, the active site topology of SAD is strikingly different from that predicted for classical CADs. Kinetic analyses of wild-type SAD and several active site mutants demonstrate the complexity of defining determinants of substrate specificity in these enzymes. These results, along with a phylogenetic analysis, support the inclusion of SAD in a plant alcohol dehydrogenase subfamily that includes cinnamaldehyde and benzaldehyde dehydrogenases. We used the SAD three-dimensional structure to model several of these SAD-like enzymes, and although their active site topologies largely mirror that of SAD, we describe a correlation between substrate specificity and amino acid substitution patterns in their active sites. The SAD structure thus provides a framework for understanding substrate specificity in this family of enzymes and for engineering new enzyme specificities. PMID:15829607
Bomati, Erin K; Noel, Joseph P
2005-05-01
We describe the three-dimensional structure of sinapyl alcohol dehydrogenase (SAD) from Populus tremuloides (aspen), a member of the NADP(H)-dependent dehydrogenase family that catalyzes the last reductive step in the formation of monolignols. The active site topology revealed by the crystal structure substantiates kinetic results indicating that SAD maintains highest specificity for the substrate sinapaldehyde. We also report substantial substrate inhibition kinetics for the SAD-catalyzed reduction of hydroxycinnamaldehydes. Although SAD and classical cinnamyl alcohol dehydrogenases (CADs) catalyze the same reaction and share some sequence identity, the active site topology of SAD is strikingly different from that predicted for classical CADs. Kinetic analyses of wild-type SAD and several active site mutants demonstrate the complexity of defining determinants of substrate specificity in these enzymes. These results, along with a phylogenetic analysis, support the inclusion of SAD in a plant alcohol dehydrogenase subfamily that includes cinnamaldehyde and benzaldehyde dehydrogenases. We used the SAD three-dimensional structure to model several of these SAD-like enzymes, and although their active site topologies largely mirror that of SAD, we describe a correlation between substrate specificity and amino acid substitution patterns in their active sites. The SAD structure thus provides a framework for understanding substrate specificity in this family of enzymes and for engineering new enzyme specificities.
Discovery and characterization of a new family of lytic polysaccharide mono-oxygenases
Hemsworth, Glyn R.; Henrissat, Bernard; Davies, Gideon J.; Walton, Paul H.
2014-01-01
Lytic polysaccharide mono-oxygenases (LPMOs) are a recently discovered class of enzymes capable of oxidizing recalcitrant polysaccharides. They currently attract much attention due to their potential use in biomass conversion, notably in the production of biofuels. Past work has identified two discrete sequence-based families of these enzymes termed AA9 (formerly GH61) and AA10 (formerly CBM33). Here we report the discovery of a third family of LPMOs. Using a chitin-degrading exemplar from Aspergillus oryzae, we show that the 3-D structure of the enzyme shares some features of the previous two classes of LPMOs, including a copper active centre featuring the histidine brace active site, but is distinct in terms of its active site details and its EPR spectroscopy. The new AA11 family expands the LPMO clan with the potential to broaden both the range of potential substrates and the types of reactive copper-oxygen species formed at the active site of LPMOs. PMID:24362702
Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase
Fenwick, Michael K.; Mehta, Angad P.; Zhang, Yang; ...
2015-03-27
Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active sitemore » metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.« less
NASA Astrophysics Data System (ADS)
Papale, D.; Baldocchi, D. D.; Loescher, H. W.; Torn, M. S.
2014-12-01
Small networks of eddy covariance sites measuring exchanges of CO2, water and energy between ecosystems and atmosphere started to be organized in Europe and USA more than 15 years ago with the AmeriFlux and EuroFlux initiatives. They were composed by less than 20 sites each, mainly over undisturbed forest and without a strong coordination between sites, in particular across the ocean. In the following years the networks grew exponentially both at continental and global level, reaching more than 500 sites few years ago and expanding the eddy covariance measurement to different ecosystem types, climate regions and management/disturbance regimes. At the same time, important steps were done in terms of cooperation and harmonization related to data processing, data description and data sharing policies, leading to inter-continental and global activities under the FLUXNET framework. Today the networks are facing a new evolution step, moving from pure research activities to something that includes also monitoring and research infrastructure characteristics. AmeriFlux and NEON (National Ecological Observatory Network) in USA and ICOS (Integrated Carbon Observation System) in Europe are opening a new phase in the eddy covariance networks: with a long term perspective, increased level of standardization and a completely open access policy, will hopefully stimulate even more global synthesis studies and a wider use of the flux measurements by other scientific communities. AmeriFlux, NEON and ICOS are also strongly involved in cross-networks harmonization activities in terms of data acquisition, data processing and data format, in order to simplify and encourage the joint use of their measurements. A brief history of the development, challenges and solutions in the organization of the different networks and their common activities will be presented, to focus then on selected scientific results that have been possible only thanks to the global integration and international collaboration and finally discuss future developments and current ongoing activities in terms of data harmonization/standardization and sharing.
Social Media and Total Joint Arthroplasty: An Analysis of Patient Utilization on Instagram.
Ramkumar, Prem N; Navarro, Sergio M; Haeberle, Heather S; Chughtai, Morad; Flynn, Megan E; Mont, Michael A
2017-09-01
The purpose of this study was to analyze the nature of shared content of total joint arthroplasty patients on Instagram. Specifically, we evaluated social media posts for: (1) perspective and timing; (2) tone; (3) focus (activities of daily living [ADLs], rehabilitation, return-to-work); and (4) the comparison between hip and knee arthroplasties. A search of the public Instagram domain was performed over a 6-month period. Total hip and knee arthroplasties (THA and TKA) were selected for the analysis using the following terms: "#totalhipreplacement," "#totalkneereplacement," and associated terms. 1287 individual public posts of human subjects were shared during the period. A categorical scoring system was utilized for media format (photo or video), time (preoperative, perioperative, or postoperative) period, tone (positive or negative), return-to-work, ADLs, rehabilitation, surgical site, radiograph image, satisfaction, and dissatisfaction. Ninety-one percent of the posts were shared during the postoperative period. Ninety-three percent of posts had a positive tone. Thirty-four percent of posts focused on both ADLs and 33.8% on rehabilitation. TKA patients shared more about their surgical site (14.5% vs 3.3%, P < .001) and rehabilitation (58.9% vs 8.8%, P < .001) than THA patients, whereas THA patients shared more about ADLs than TKA patients (60.5% vs 7.6%, P < .001). When sharing their experience on Instagram, arthroplasty patients did so with a positive tone, starting a week after surgery. TKA posts focused more on rehabilitation and wound healing than THA patients, whereas THA patients shared more posts on ADLs. The analysis of social media posts provides insight into what matters to patients after total joint arthroplasty. Copyright © 2017 Elsevier Inc. All rights reserved.
Carnegie Science Academy Web Site
NASA Astrophysics Data System (ADS)
Kotwicki, John; Atzinger, Joe; Turso, Denise
1997-11-01
The Carnegie Science Academy is a professional society "For Teens...By Teens" at the Carnegie Science Center in Pittsburgh. The CSA Web Site [ http://csa.clpgh.org ] is designed for teens who have an interest in science and technology. This online or virtual science academy provides resources for teens in high school science classes. The Web site also allows students around the world to participate and communicate with other students, discuss current events in science, share opinions, find answers to questions, or make online friends. Visitors can enjoy the main components of the site or sign up for a free membership which allows access to our chat room for monthly meeting, online newsletter, members forum, and much more. Main components to the site include a spot for cool links and downloads, available for any visitor to download or view. Online exhibits are created by students to examine and publish an area of study and also allow teachers to easily post classroom activities as exhibits by submitting pictures and text. Random Access, the interactive part of the academy, allows users to share ideas and opinions. Planet CSA focuses on current events in science and the academy. In the future the CSA Web site will become a major resource for teens and science teachers providing materials that will allow students to further enhance their interest and experiences in science.
Activity-based proteomics of enzyme superfamilies: serine hydrolases as a case study.
Simon, Gabriel M; Cravatt, Benjamin F
2010-04-09
Genome sequencing projects have uncovered thousands of uncharacterized enzymes in eukaryotic and prokaryotic organisms. Deciphering the physiological functions of enzymes requires tools to profile and perturb their activities in native biological systems. Activity-based protein profiling has emerged as a powerful chemoproteomic strategy to achieve these objectives through the use of chemical probes that target large swaths of enzymes that share active-site features. Here, we review activity-based protein profiling and its implementation to annotate the enzymatic proteome, with particular attention given to probes that target serine hydrolases, a diverse superfamily of enzymes replete with many uncharacterized members.
Kasper, Helmut; Lehrer, Mark; Mühlbacher, Jürgen; Müller, Barbara
2013-02-01
This qualitative field study investigated cross-site knowledge sharing in a small sample of multinational corporations in three different MNC business contexts (global, multidomestic, transnational). The results disclose heterogeneous "worlds" of MNC knowledge sharing, ultimately raising the question as to whether the whole concept of MNC knowledge sharing covers a sufficiently unitary phenomenon to be meaningful. We derive a non-exhaustive typology of MNC knowledge-sharing practices: self-organizing knowledge sharing, technocratic knowledge sharing, and best practice knowledge sharing. Despite its limitations, this typology helps to elucidate a number of issues, including the latent conflict between two disparate theories of MNC knowledge sharing, namely "sender-receiver" and "social learning" theories (Noorderhaven & Harzing, 2009). More generally, we develop the term "knowledge contextualization" to highlight the way that firm-specific organizational features pre-define which knowledge is considered to be of special relevance for intra-organizational sharing.
ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.
Konc, Janez; Janežič, Dušanka
2014-07-01
The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
Alternative Fuels Data Center: Truck Stop Electrification Site Data
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Irish Medical Student Culture and the Performance of Masculinity, C.1880-1930
ERIC Educational Resources Information Center
Kelly, Laura
2017-01-01
In recent years, there have been valuable studies of medical education that have highlighted the importance of shared educational activities and the changing image of the student. Less attention has been paid to how masculine ideals were passed on to students and how educational and extra-curricular spheres became sites for the maintenance of…
Participation, Deliberate Learning and Discourses of Learning Online
ERIC Educational Resources Information Center
Barton, David
2012-01-01
This paper uses a study of the photo-sharing website Flickr to examine new online spaces for writing. On this site, people write titles and descriptions for their photos, they annotate their photos with semantic tags, they provide profiles of themselves and they comment on other people's photos. In these activities, people are engaging in new…
Properties of Teacher Networks in Twitter: Are They Related to Community-Based Peer Production?
ERIC Educational Resources Information Center
Macià, Maria; Garcia, Iolanda
2017-01-01
Teachers participate in social networking sites to share knowledge and collaborate with other teachers to create education-related content. In this study we selected several communities in order to better understand the networks that these participants establish in Twitter and the role that the social network plays in their activity within the…
ERIC Educational Resources Information Center
Forkosh-Baruch, Alona; Hershkovitz, Arnon
2012-01-01
The purpose of this study is to empirically examine cases in which Social Networking Sites (SNS) are being utilized for scholarly purposes by higher-education institutes in Israel. The research addresses questions regarding content patterns, activity patterns, and interactivity within Facebook and Twitter accounts of these institutes. Research…
ERIC Educational Resources Information Center
Licona, Adela C.; Gonzales, J. Sarah
2013-01-01
This article highlights Education/Connection/Action (ECA), a locally developed community pedagogy deployed at a youth activism summer camp that served as a site for a community/academic teaching and research collaboration. Youth considered connections between a set of issues, including a local ban on Ethnic Studies, the School-to-Prison Pipeline,…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Castillo, Darina; Carpenter, Cliff; Linard, Joshua
Story Maps are being used in both public and private sectors to convey information to stakeholders, create enterprise platforms, and assist in decision making. Story Maps are web applications that combine maps, narrative text, images, and multimedia content to provide information. These applications provide a user-friendly platform to share the remarkable history of our sites, the complexity of their contamination and remediation, successes we achieve in our LTS&M activities, and even the challenges we face as we aim to fulfill our mission.
La Barbera, Daniele; La Paglia, Filippo; Valsavoia, Rosaria
2009-01-01
In recent decades, the rapid development of innovative Internet-based communication technologies created a new field of academic study among scholars. Particularly, the attention of researchers is focusing on new ways to form relationship-thought social web. Social Network sites constitute a new form of web communities, where people meet and share interests and activities. Due to exponential growth of these sites, an increasing number of scholars are beginning to study the emergent phenomena in order to identify any psychopathological risk related to use of social web, such as addiction. This article examines the recent literature about this issue.
Computer-Mediated Social Support for Physical Activity: A Content Analysis.
Stragier, Jeroen; Mechant, Peter; De Marez, Lieven; Cardon, Greet
2018-02-01
Online fitness communities are a recent phenomenon experiencing growing user bases. They can be considered as online social networks in which recording, monitoring, and sharing of physical activity (PA) are the most prevalent practices. They have added a new dimension to the social experience of PA in which online peers function as virtual PA partners or supporters. However, research into seeking and receiving computer-mediated social support for PA is scarce. Our aim was to study to what extent using online fitness communities and sharing physical activities with online social networks results in receiving various types of online social support. Two databases, one containing physical activities logged with Strava and one containing physical activities logged with RunKeeper and shared on Twitter, were investigated for occurrence and type of social support, by means of a deductive content analysis. Results indicate that social support delivered through Twitter is not particularly extensive. On Strava, social support is significantly more prevalent. Especially esteem support, expressed as compliments for the accomplishment of an activity, is provided on both Strava and Twitter. The results demonstrate that social media have potential as a platform used for providing social support for PA, but differences among various social network sites can be substantial. Especially esteem support can be expected, in contrast to online health communities, where information support is more common.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dreimanis, A.
This report considers the problem of multilevel consensus building for siting and construction of shared multinational/regional repositories for radioactive waste (RW) deep disposal. In the siting of a multinational repository there appears an essential innovative component of stakeholder consensus building, namely: to reach consent - political, social, economic, ecological - among international partners, in addition to solving the whole set of intra-national consensus building items. An entire partnering country is considered as a higher-level stakeholder - the national stakeholder, represented by the national government, being faced to simultaneous seeking an upward (international) and a downward (intra-national) consensus in a psychologicallymore » stressed environment, possibly being characterized by diverse political, economic and social interests. The following theses as a possible interdisciplinary approach towards building of shared understanding and stakeholder consensus on the international scale of RW disposal are forwarded and developed: a) building of international stakeholder consensus would be promoted by activating and diversifying on the international scale multilateral interactions between intra- and international stakeholders, including web-based networks of the RW disposal site investigations and decision-making, as well as networks for international cooperation among government authorities in nuclear safety, b) gradual progress in intergovernmental consensus and reaching multilateral agreements on shared deep repositories will be the result of democratic dialogue, via observing the whole set of various interests and common resolving of emerged controversies by using advanced synergetic approaches of conflict resolution, c) cross-cultural thinking and world perception, mental flexibility, creativity and knowledge are considered as basic prerogatives for gaining a higher level of mutual understanding and consensus for seeking further consensus, for advancing the preparedness to act together, and ultimately - for achieving desired shared goals. It is proposed that self-organized social learning will make it possible to promote adequate perception of risk and prevent, by diminishing uncertainties and unknown factors, social amplification of an imagined risk, as well as to increase the trust level and facilitate more adequate equity perception. The proposed approach to the multilevel stakeholder consensus building on international scale is extrapolated to the present-day activities of siting of such near-surface RW disposal facilities which supposedly could have non-negligible trans-boundary impact. A multilevel stakeholder interaction process is considered for the case of resolving of emerged problems in site selection for the planned near-surface RW repository in vicinity of the Lithuanian-Latvian border foreseen for disposal of short lived low- and intermediate level waste arising from the decommissioning of the Ignalina Nuclear Power Plant. (authors)« less
NASA Astrophysics Data System (ADS)
Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian
2009-06-01
Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.
Leuthaeuser, Janelle B; Knutson, Stacy T; Kumar, Kiran; Babbitt, Patricia C; Fetrow, Jacquelyn S
2015-09-01
The development of accurate protein function annotation methods has emerged as a major unsolved biological problem. Protein similarity networks, one approach to function annotation via annotation transfer, group proteins into similarity-based clusters. An underlying assumption is that the edge metric used to identify such clusters correlates with functional information. In this contribution, this assumption is evaluated by observing topologies in similarity networks using three different edge metrics: sequence (BLAST), structure (TM-Align), and active site similarity (active site profiling, implemented in DASP). Network topologies for four well-studied protein superfamilies (enolase, peroxiredoxin (Prx), glutathione transferase (GST), and crotonase) were compared with curated functional hierarchies and structure. As expected, network topology differs, depending on edge metric; comparison of topologies provides valuable information on structure/function relationships. Subnetworks based on active site similarity correlate with known functional hierarchies at a single edge threshold more often than sequence- or structure-based networks. Sequence- and structure-based networks are useful for identifying sequence and domain similarities and differences; therefore, it is important to consider the clustering goal before deciding appropriate edge metric. Further, conserved active site residues identified in enolase and GST active site subnetworks correspond with published functionally important residues. Extension of this analysis yields predictions of functionally determinant residues for GST subgroups. These results support the hypothesis that active site similarity-based networks reveal clusters that share functional details and lay the foundation for capturing functionally relevant hierarchies using an approach that is both automatable and can deliver greater precision in function annotation than current similarity-based methods. © 2015 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.
Leuthaeuser, Janelle B; Knutson, Stacy T; Kumar, Kiran; Babbitt, Patricia C; Fetrow, Jacquelyn S
2015-01-01
The development of accurate protein function annotation methods has emerged as a major unsolved biological problem. Protein similarity networks, one approach to function annotation via annotation transfer, group proteins into similarity-based clusters. An underlying assumption is that the edge metric used to identify such clusters correlates with functional information. In this contribution, this assumption is evaluated by observing topologies in similarity networks using three different edge metrics: sequence (BLAST), structure (TM-Align), and active site similarity (active site profiling, implemented in DASP). Network topologies for four well-studied protein superfamilies (enolase, peroxiredoxin (Prx), glutathione transferase (GST), and crotonase) were compared with curated functional hierarchies and structure. As expected, network topology differs, depending on edge metric; comparison of topologies provides valuable information on structure/function relationships. Subnetworks based on active site similarity correlate with known functional hierarchies at a single edge threshold more often than sequence- or structure-based networks. Sequence- and structure-based networks are useful for identifying sequence and domain similarities and differences; therefore, it is important to consider the clustering goal before deciding appropriate edge metric. Further, conserved active site residues identified in enolase and GST active site subnetworks correspond with published functionally important residues. Extension of this analysis yields predictions of functionally determinant residues for GST subgroups. These results support the hypothesis that active site similarity-based networks reveal clusters that share functional details and lay the foundation for capturing functionally relevant hierarchies using an approach that is both automatable and can deliver greater precision in function annotation than current similarity-based methods. PMID:26073648
Zhao, Haiyan; Lin, Zihan; Lynn, Anna Y.; Varnado, Brittany; Beutler, John A.; Murelli, Ryan P.; Le Grice, Stuart F. J.; Tang, Liang
2015-01-01
Many dsDNA viruses encode DNA-packaging terminases, each containing a nuclease domain that resolves concatemeric DNA into genome-length units. Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, and share a two-metal-ion catalytic mechanism. Here we show that residue K428 of a bacteriophage terminase gp2 nuclease domain mediates binding of the metal cofactor Mg2+. A K428A mutation allows visualization, at high resolution, of a metal ion binding mode with a coupled-octahedral configuration at the active site, exhibiting an unusually short metal-metal distance of 2.42 Å. Such proximity of the two metal ions may play an essential role in catalysis by generating a highly positive electrostatic niche to enable formation of the negatively charged pentacovalent phosphate transition state, and provides the structural basis for distinguishing Mg2+ from Ca2+. Using a metal ion chelator β-thujaplicinol as a molecular probe, we observed a second mode of metal ion binding at the active site, mimicking the DNA binding state. Arrangement of the active site residues differs drastically from those in RNase H-like nucleases, suggesting a drifting of the active site configuration during evolution. The two distinct metal ion binding modes unveiled mechanistic details of the two-metal-ion catalysis at atomic resolution. PMID:26450964
Code of Federal Regulations, 2011 CFR
2011-01-01
... the financial results of each grant. Financial Reporting will be on an accrual basis. (b) Records... conditions established by the Grantor. Provided, however, that the proportionate share of any grant funds... compensating the Federal Government for its fair share of the property. The Federal share of the property shall...
Entextualising mourning on Facebook: stories of grief as acts of sharing
NASA Astrophysics Data System (ADS)
Giaxoglou, Korina
2015-04-01
Web 2.0 mourning is said to afford increased opportunities for the deceased's and mourners' visibility as well as create in the bereaved an increased sense of social support through the participatory entextualisation of mourning. So far, however, there has been little systematic attention to the uses of narrative in social network sites. The present article addresses this gap by providing an analysis of entextualised moments of mourning as stories shared by a single author over a six-month period on a Facebook Rest in Peace memorial group. The article foregrounds heterogeneity in narrative activity across posts, linking diversity in ways of telling to different types of the online mourner's positioning at three interrelated levels of discourse construction: (1) the representation of the event of death, (2) the alignment (or disalignment) with the dead and the networked mourners and (3) the poster's self. It is argued that telling stories on Facebook memorial sites constitutes an act of sharing affording networked individuals resources for making meaning out of the meaninglessness of a loved one's death in ways that can help render the painful experience of loss tellable and also create a sense of ambient affiliation or affinity with networked mourners.
Unidata's Vision for Providing Comprehensive and End-to-end Data Services
NASA Astrophysics Data System (ADS)
Ramamurthy, M. K.
2009-05-01
This paper presents Unidata's vision for providing comprehensive, well-integrated, and end-to-end data services for the geosciences. These include an array of functions for collecting, finding, and accessing data; data management tools for generating, cataloging, and exchanging metadata; and submitting or publishing, sharing, analyzing, visualizing, and integrating data. When this vision is realized, users no matter where they are or how they are connected to the Internetwill be able to find and access a plethora of geosciences data and use Unidata-provided tools and services both productively and creatively in their research and education. What that vision means for the Unidata community is elucidated by drawing a simple analogy. Most of users are familiar with Amazon and eBay e-commerce sites and content sharing sites like YouTube and Flickr. On the eBay marketplace, people can sell practically anything at any time and buyers can share their experience of purchasing a product or the reputation of a seller. Likewise, at Amazon, thousands of merchants sell their goods and millions of customers not only buy those goods, but provide a review or opinion of the products they buy and share their experiences as purchasers. Similarly, YouTube and Flickr are sites tailored to video- and photo-sharing, respectively, where users can upload their own content and share it with millions of other users, including family and friends. What all these sites, together with social-networking applications like MySpace and Facebook, have enabled is a sense of a virtual community in which users can search and browse products or content, comment and rate those products from anywhere, at any time, and via any Internet- enabled device like an iPhone, laptop, or a desktop computer. In essence, these enterprises have fundamentally altered people's buying modes and behavior toward purchases. Unidata believes that similar approaches, appropriately tailored to meet the needs of the scientific community, can be adopted to provide and share geosciences data and actively collaborate in the future. For example, future case-study data access systems, in addition to providing datasets and tools, will provide services that allow users to provide commentaries on a weather event, say a hurricane, as well as provide feedback on the quality, usefulness, and interpretation of the datasets through integrated blogs, forums, and Wikis, along with uploading and sharing products they derive, ancillary materials that users might have gathered (such as photos and videos from the storm), and publications and curricular materials they develop, all through a single data portal. In essence, such case study collections will be "living" or dynamic, allowing users to be also contributors as they add value to and grow existing case study collections.
Lenz, Stefan A P; Wetmore, Stacey D
2016-02-09
Human alkyladenine DNA glycosylase (AAG) functions as part of the base excision repair (BER) pathway by cleaving the N-glycosidic bond that connects nucleobases to the sugar-phosphate backbone in DNA. AAG targets a range of structurally diverse purine lesions using nonspecific DNA-protein π-π interactions. Nevertheless, the enzyme discriminates against the natural purines and is inhibited by pyrimidine lesions. This study uses molecular dynamics simulations and seven different neutral or charged substrates, inhibitors, or canonical purines to probe how the bound nucleotide affects the conformation of the AAG active site, and the role of active site residues in dictating substrate selectivity. The neutral substrates form a common DNA-protein hydrogen bond, which results in a consistent active site conformation that maximizes π-π interactions between the aromatic residues and the nucleobase required for catalysis. Nevertheless, subtle differences in DNA-enzyme contacts for different neutral substrates explain observed differential catalytic efficiencies. In contrast, the exocyclic amino groups of the natural purines clash with active site residues, which leads to catalytically incompetent DNA-enzyme complexes due to significant reorganization of active site water. Specifically, water resides between the A nucleobase and the active site aromatic amino acids required for catalysis, while a shift in the position of the general base (E125) repositions (potentially nucleophilic) water away from G. Despite sharing common amino groups, the methyl substituents in cationic purine lesions (3MeA and 7MeG) exhibit repulsion with active site residues, which repositions the damaged bases in the active site in a manner that promotes their excision. Overall, we provide a structural explanation for the diverse yet discriminatory substrate selectivity of AAG and rationalize key kinetic data available for the enzyme. Specifically, our results highlight the complex interplay of many different DNA-protein interactions used by AAG to facilitate BER, as well as the crucial role of the general base and water (nucleophile) positioning. The insights gained from our work will aid the understanding of the function of other enzymes that use flexible active sites to exhibit diverse substrate specificity.
McClellan, Michael J.; Wood, C. David; Ojeniyi, Opeoluwa; Cooper, Tim J.; Kanhere, Aditi; Arvey, Aaron; Webb, Helen M.; Palermo, Richard D.; Harth-Hertle, Marie L.; Kempkes, Bettina; Jenner, Richard G.; West, Michelle J.
2013-01-01
Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors. PMID:24068937
Kasper, Helmut; Lehrer, Mark; Mühlbacher, Jürgen; Müller, Barbara
2013-01-01
This qualitative field study investigated cross-site knowledge sharing in a small sample of multinational corporations in three different MNC business contexts (global, multidomestic, transnational). The results disclose heterogeneous “worlds” of MNC knowledge sharing, ultimately raising the question as to whether the whole concept of MNC knowledge sharing covers a sufficiently unitary phenomenon to be meaningful. We derive a non-exhaustive typology of MNC knowledge-sharing practices: self-organizing knowledge sharing, technocratic knowledge sharing, and best practice knowledge sharing. Despite its limitations, this typology helps to elucidate a number of issues, including the latent conflict between two disparate theories of MNC knowledge sharing, namely “sender–receiver” and “social learning” theories (Noorderhaven & Harzing, 2009). More generally, we develop the term “knowledge contextualization” to highlight the way that firm-specific organizational features pre-define which knowledge is considered to be of special relevance for intra-organizational sharing. PMID:27087759
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tomasic, Ivan B.; Metcalf, Matthew C.; Guce, Abigail I.
2010-09-03
The human lysosomal enzymes {alpha}-galactosidase ({alpha}-GAL, EC 3.2.1.22) and {alpha}-N-acetylgalactosaminidase ({alpha}-NAGAL, EC 3.2.1.49) share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of {alpha}-GAL and {alpha}-NAGAL. The engineered {alpha}-GAL (which we call {alpha}-GALSA) retains the antigenicity of {alpha}-GAL but has acquired the enzymatic specificity of {alpha}-NAGAL. Conversely, the engineered {alpha}-NAGAL (which we call {alpha}-NAGAL{sup EL}) retains the antigenicity of {alpha}-NAGAL but has acquired themore » enzymatic specificity of the {alpha}-GAL enzyme. Comparison of the crystal structures of the designed enzyme {alpha}-GAL{sup SA} to the wild-type enzymes shows that active sites of {alpha}-GAL{sup SA} and {alpha}-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease.« less
ERIC Educational Resources Information Center
Conole, Grainne; Galley, Rebecca; Culver, Juliette
2011-01-01
This paper describes a new social networking site, Cloudworks, which has been developed to enable discussion and sharing of learning and teaching ideas/designs and to promote reflective academic practice. The site aims to foster new forms of social and participatory practices (peer critiquing, sharing, user-generated content, aggregation, and…
Spatial overlap links seemingly unconnected genotype-matched TB cases in rural Uganda
Kato-Maeda, Midori; Emperador, Devy M.; Wandera, Bonnie; Mugagga, Olive; Crandall, John; Janes, Michael; Marquez, Carina; Kamya, Moses R.; Charlebois, Edwin D.; Havlir, Diane V.
2018-01-01
Introduction Incomplete understanding of TB transmission dynamics in high HIV prevalence settings remains an obstacle for prevention. Understanding where transmission occurs could provide a platform for case finding and interrupting transmission. Methods From 2012–2015, we sought to recruit all adults starting TB treatment in a Ugandan community. Participants underwent household (HH) contact investigation, and provided names of social contacts, sites of work, healthcare and socializing, and two sputum samples. Mycobacterium tuberculosis culture-positive specimens underwent 24-loci MIRU-VNTR and spoligotyping. We sought to identify epidemiologic links between genotype-matched cases by analyzing social networks and mapping locations where cases reported spending ≥12 hours over the one-month pre-treatment. Sites of spatial overlap (≤100m) between genotype-matched cases were considered potential transmission sites. We analyzed social networks stratified by genotype clustering status, with cases linked by shared locations, and compared network density by location type between clustered vs. non-clustered cases. Results Of 173 adults with TB, 131 (76%) were enrolled, 108 provided sputum, and 84/131 (78%) were MTB culture-positive: 52% (66/131) tested HIV-positive. Of 118 adult HH contacts, 105 (89%) were screened and 3 (2.5%) diagnosed with active TB. Overall, 33 TB cases (39%) belonged to 15 distinct MTB genotype-matched clusters. Within each cluster, no cases shared a HH or reported shared non-HH contacts. In 6/15 (40%) clusters, potential epidemiologic links were identified by spatial overlap at specific locations: 5/6 involved health care settings. Genotype-clustered TB social networks had significantly greater network density based on shared clinics (p<0.001) and decreased density based on shared marketplaces (p<0.001), compared to non-clustered networks. Conclusions In this molecular epidemiologic study, links between MTB genotype-matched cases were only identifiable via shared locations, healthcare locations in particular, rather than named contacts. This suggests most transmission is occurring between casual contacts, and emphasizes the need for improved infection control in healthcare settings in rural Africa. PMID:29438413
Via Dialogue or Messaging: How Air Force Public Affairs Is Leveraging Social Media
2010-12-01
or “blogs”; (2) content-sharing sites (e.g., YouTube, Flickr, Wikis); (3) Micro-blogs (Twitter, Google Buzz); and (4) Social networking sites (e.g...aforementioned categories of social media (blogs, content sharing, micro-blogs, social networking sites , and the optional “other”) are to the overall PA...The results indicate that social networking sites (e.g., Facebook, LinkedIn) were clearly the most utilized by respondents, in terms of posting and
Nishimura, R; Li, W; Kashishian, A; Mondino, A; Zhou, M; Cooper, J; Schlessinger, J
1993-11-01
Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.
Chibani, Kamel; Tarrago, Lionel; Gualberto, José Manuel; Wingsle, Gunnar; Rey, Pascal; Jacquot, Jean-Pierre; Rouhier, Nicolas
2012-01-01
Plant thioredoxins (Trxs) constitute a complex family of thiol oxidoreductases generally sharing a WCGPC active site sequence. Some recently identified plant Trxs (Clot, Trx-like1 and -2, Trx-lilium1, -2, and -3) display atypical active site sequences with altered residues between the two conserved cysteines. The transcript expression patterns, subcellular localizations, and biochemical properties of some representative poplar (Populus spp.) isoforms were investigated. Measurements of transcript levels for the 10 members in poplar organs indicate that most genes are constitutively expressed. Using transient expression of green fluorescent protein fusions, Clot and Trx-like1 were found to be mainly cytosolic, whereas Trx-like2.1 was located in plastids. All soluble recombinant proteins, except Clot, exhibited insulin reductase activity, although with variable efficiencies. Whereas Trx-like2.1 and Trx-lilium2.2 were efficiently regenerated both by NADPH-Trx reductase and glutathione, none of the proteins were reduced by the ferredoxin-Trx reductase. Only Trx-like2.1 supports the activity of plastidial thiol peroxidases and methionine sulfoxide reductases employing a single cysteine residue for catalysis and using a glutathione recycling system. The second active site cysteine of Trx-like2.1 is dispensable for this reaction, indicating that the protein possesses a glutaredoxin-like activity. Interestingly, the Trx-like2.1 active site replacement, from WCRKC to WCGPC, suppresses its capacity to use glutathione as a reductant but is sufficient to allow the regeneration of target proteins employing two cysteines for catalysis, indicating that the nature of the residues composing the active site sequence is crucial for substrate selectivity/recognition. This study provides another example of the cross talk existing between the glutathione/glutaredoxin and Trx-dependent pathways. PMID:22523226
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
2013-03-01
This report summarizes the 2012 annual inspection, sampling, measurement, and maintenance activities performed at the Salmon, Mississippi, Site (Salmon site). The draft Long-Term Surveillance and Maintenance Plan for the Salmon Site, Lamar County, Mississippi (DOE 2007) specifies the submittal of an annual report of site activities with the results of sample analyses. A revised plan is in preparation. The Long-Term Surveillance Plan for the Salmon, Mississippi, Site is intended for release in 2013. The Salmon site consists of 1,470 acres. The site is located in Lamar County, Mississippi, approximately 10 miles west of Purvis, Mississippi, and about 21 miles southwestmore » of Hattiesburg, Mississippi The State of Mississippi owns the surface real estate subject to certain restrictions related to subsurface penetration. The State is the surface operator; the Mississippi Forestry Commission is its agent. The federal government owns the subsurface real estate (including minerals and some surface features), shares right-of-entry easements with the State, and retains rights related to subsurface monitoring. The U.S. Department of Energy (DOE) Office of Legacy Management (LM), a successor agency to the U.S. Atomic Energy Commission, is responsible for the long-term surveillance of the subsurface real estate« less
Tie, Jian-Ke; Jin, Da-Yun; Stafford, Darrel W.
2014-01-01
Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions. PMID:24532791
Tie, Jian-Ke; Jin, Da-Yun; Stafford, Darrel W
2014-03-28
Vitamin K epoxide reductase complex subunit 1 (VKORC1) reduces vitamin K epoxide in the vitamin K cycle for post-translational modification of proteins that are involved in a variety of biological functions. However, the physiological function of VKORC1-like 1 (VKORC1L1), a paralogous enzyme sharing about 50% protein identity with VKORC1, is unknown. Here we determined the structural and functional differences of these two enzymes using fluorescence protease protection (FPP) assay and an in vivo cell-based activity assay. We show that in vivo VKORC1L1 reduces vitamin K epoxide to support vitamin K-dependent carboxylation as efficiently as does VKORC1. However, FPP assays show that unlike VKORC1, VKORC1L1 is a four-transmembrane domain protein with both its termini located in the cytoplasm. Moreover, the conserved loop cysteines, which are not required for VKORC1 activity, are essential for VKORC1L1's active site regeneration. Results from domain exchanges between VKORC1L1 and VKORC1 suggest that it is VKORC1L1's overall structure that uniquely allows for active site regeneration by the conserved loop cysteines. Intermediate disulfide trapping results confirmed an intra-molecular electron transfer pathway for VKORC1L1's active site reduction. Our results allow us to propose a concerted action of the four conserved cysteines of VKORC1L1 for active site regeneration; the second loop cysteine, Cys-58, attacks the active site disulfide, forming an intermediate disulfide with Cys-139; the first loop cysteine, Cys-50, attacks the intermediate disulfide resulting in active site reduction. The different membrane topologies and reaction mechanisms between VKORC1L1 and VKORC1 suggest that these two proteins might have different physiological functions.
Tauroursodeoxycholic acid binds to the G-protein site on light activated rhodopsin.
Lobysheva, E; Taylor, C M; Marshall, G R; Kisselev, O G
2018-05-01
The heterotrimeric G-protein binding site on G-protein coupled receptors remains relatively unexplored regarding its potential as a new target of therapeutic intervention or as a secondary site of action by the existing drugs. Tauroursodeoxycholic acid bears structural resemblance to several compounds that were previously identified to specifically bind to the light-activated form of the visual receptor rhodopsin and to inhibit its activation of transducin. We show that TUDCA stabilizes the active form of rhodopsin, metarhodopsin II, and does not display the detergent-like effects of common amphiphilic compounds that share the cholesterol scaffold structure, such as deoxycholic acid. Computer docking of TUDCA to the model of light-activated rhodopsin revealed that it interacts using similar mode of binding to the C-terminal domain of transducin alpha subunit. The ring regions of TUDCA made hydrophobic contacts with loop 3 region of rhodopsin, while the tail of TUDCA is exposed to solvent. The results show that TUDCA interacts specifically with rhodopsin, which may contribute to its wide-ranging effects on retina physiology and as a potential therapeutic compound for retina degenerative diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Final Report: Sensorpedia Phases 1 and 2
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gorman, Bryan L; Resseguie, David R
2010-08-01
Over the past several years, ORNL has been actively involved in research to formalize the engineering principles and best practices behind emerging social media and social networking concepts to solve real-time data sharing problems for national security and defense, public health and safety, environmental and infrastructure awareness, and disaster preparedness and response. Sensorpedia, an ORNL web site, is a practical application of several key social media principles. Dubbed the Wikipedia for sensors, Sensorpedia is currently in limited BETA testing and was selected in 2009 by Federal Computer Week as one of the government s top 10 social networking sites.
Konrad, Christopher P.; Voss, Frank D.
2012-01-01
The streamflow-gaging network in the Puget Sound basin was analyzed for its capacity to monitor stormwater in small streams. The analysis consisted of an inventory of active and inactive gages and an evaluation of the coverage and resolution of the gaging network with an emphasis on lowland areas. The active gaging network covers much of the Puget Lowland largely by gages located at sites on larger streams and rivers. Assessments of stormwater impacts and management will likely require streamflow information with higher spatial resolution than provided by the current gaging network. Monitoring that emphasizes small streams in combination with approaches for estimating streamflow at ungaged sites provides an alternative to expanding the current gaging network that can improve the spatial resolution of streamflow information in the region. The highest priority gaps in the gaging network are low elevation basins close to the Puget Sound shoreline and sites that share less than 10 percent of the drainage area of an active gage. Although small, lowland sites with long records of streamflow are particularly valuable to maintain in the region, other criteria for prioritizing sites in the gaging network should be based on the specific questions that stormwater managers need to answer.
ESS (Employee Self Service) E-Travel Online Login IRIS FIN/PROC Login IRIS HRM Login LearnAlaska SFOA SharePoint Site TRIPS (Traveler Integrated Profile System) Vendor Self Service (VSS) Resources Alaska & Resources Manuals Payment Detail Report Salary Schedules SFOA SharePoint Site (SOA Only) Training
Information Seeking in Social Media: A Review of YouTube for Sedentary Behavior Content.
Knight, Emily; Intzandt, Brittany; MacDougall, Alicia; Saunders, Travis J
2015-01-20
The global prevalence of sedentary lifestyles is of grave concern for public health around the world. Moreover, the health risk of sedentary behaviors is of growing interest for researchers, clinicians, and the general public as evidence demonstrates that prolonged amounts of sedentary time increases risk for lifestyle-related diseases. There is a growing trend in the literature that reports how social media can facilitate knowledge sharing and collaboration. Social sites like YouTube facilitate the sharing of media content between users. The purpose of this project was to identify sedentary behavior content on YouTube and describe features of this content that may impact the effectiveness of YouTube for knowledge translation. YouTube was searched on a single day by 3 independent reviewers for evidence-based sedentary behavior content. Subjective data (eg, video purpose, source, and activity type portrayed) and objective data (eg, number of views, comments, shares, and length of the video) were collected from video. In total, 106 videos met inclusion criteria. Videos were uploaded from 13 countries around the globe (ie, Australia, Barbados, Belgium, Canada, Colombia, Kenya, New Zealand, Russia, South Africa, Spain, Ukraine, United Kingdom, United States). The median video length was 3:00 minutes: interquartile range (IQR) 1:44-5:40. On average, videos had been on YouTube for 15.0 months (IQR 6.0-27.5) and had been viewed 239.0 times (IQR 44.5-917.5). Videos had remarkably low numbers of shares (median 0) and comments (median 1). Only 37.7% (40/106) of videos portrayed content on sedentary behaviors, while the remaining 66 videos portrayed physical activity or a mix of behaviors. Academic/health organizations (39.6%, 42/106) and individuals (38.7%, 41/106) were the most prevalent source of videos, and most videos (67.0%, 71/106) aimed to educate viewers about the topic. This study explored sedentary behavior content available on YouTube. Findings demonstrate that there is confusion between physical activity and sedentary behaviors, that content is being uploaded to the site from around the globe, that content is primarily from health organizations and individuals with the purpose of educating fellow users, but that low views, comments, and shares suggest that sedentary behavior content is relatively underutilized on YouTube. Future research may wish to leverage social platforms, such as YouTube, to facilitate implementation and sharing of evidence-based sedentary behavior content.
Information Seeking in Social Media: A Review of YouTube for Sedentary Behavior Content
2015-01-01
Background The global prevalence of sedentary lifestyles is of grave concern for public health around the world. Moreover, the health risk of sedentary behaviors is of growing interest for researchers, clinicians, and the general public as evidence demonstrates that prolonged amounts of sedentary time increases risk for lifestyle-related diseases. There is a growing trend in the literature that reports how social media can facilitate knowledge sharing and collaboration. Social sites like YouTube facilitate the sharing of media content between users. Objective The purpose of this project was to identify sedentary behavior content on YouTube and describe features of this content that may impact the effectiveness of YouTube for knowledge translation. Methods YouTube was searched on a single day by 3 independent reviewers for evidence-based sedentary behavior content. Subjective data (eg, video purpose, source, and activity type portrayed) and objective data (eg, number of views, comments, shares, and length of the video) were collected from video. Results In total, 106 videos met inclusion criteria. Videos were uploaded from 13 countries around the globe (ie, Australia, Barbados, Belgium, Canada, Colombia, Kenya, New Zealand, Russia, South Africa, Spain, Ukraine, United Kingdom, United States). The median video length was 3:00 minutes: interquartile range (IQR) 1:44-5:40. On average, videos had been on YouTube for 15.0 months (IQR 6.0-27.5) and had been viewed 239.0 times (IQR 44.5-917.5). Videos had remarkably low numbers of shares (median 0) and comments (median 1). Only 37.7% (40/106) of videos portrayed content on sedentary behaviors, while the remaining 66 videos portrayed physical activity or a mix of behaviors. Academic/health organizations (39.6%, 42/106) and individuals (38.7%, 41/106) were the most prevalent source of videos, and most videos (67.0%, 71/106) aimed to educate viewers about the topic. Conclusions This study explored sedentary behavior content available on YouTube. Findings demonstrate that there is confusion between physical activity and sedentary behaviors, that content is being uploaded to the site from around the globe, that content is primarily from health organizations and individuals with the purpose of educating fellow users, but that low views, comments, and shares suggest that sedentary behavior content is relatively underutilized on YouTube. Future research may wish to leverage social platforms, such as YouTube, to facilitate implementation and sharing of evidence-based sedentary behavior content. PMID:25604433
Effects of intraguild predators on nest-site selection by prey.
Huang, Wen-San; Pike, David A
2012-01-01
Nest-site selection involves tradeoffs between the risk of predation (on females and/or nests) and nest-site quality (microenvironment), and consequently suitable nesting sites are often in limited supply. Interactions with "classical" predators (e.g., those not competing for shared resources) can strongly influence nest-site selection, but whether intraguild predation also influences this behavior is unknown. We tested whether risk of predation from an intraguild predator [the diurnal scincid lizard Eutropis (Mabuya) longicaudata] influences nest-site selection by its prey (the nocturnal gecko Gekko hokouensis) on Orchid Island, Taiwan. These two species putatively compete for shared resources, including invertebrate prey and nesting microhabitat, but the larger E. longicaudata also predates G. hokouensis (but not its hard-shelled eggs). Both species nested within a concrete wall containing a series of drainage holes that have either one ("closed-in") or two openings ("open"). In allopatry, E. longicaudata preferred to nest within holes that were plugged by debris (thereby protecting eggs from water intrusion), whereas G. hokouensis selected holes that were open at both ends (facilitating escape from predators). When we experimentally excluded E. longicaudata from its preferred nesting area, G. hokouensis not only nested in higher abundances, but also modified its nest-site selection, such that communal nesting was more prevalent and both open and closed-in holes were used equally. Egg viability was unaffected by the choice of hole type, but was reduced slightly (by 7%) in the predator exclusion area (presumably due to higher local incubation temperatures). Our field experiment demonstrates that intraguild predators can directly influence the nest density of prey by altering maternal nest-site selection behavior, even when the predator and prey are active at different times of day and the eggs are not at risk of predation.
Menchon, Grégory; Prota, Andrea E; Lucena-Agell, Daniel; Bucher, Pascal; Jansen, Rolf; Irschik, Herbert; Müller, Rolf; Paterson, Ian; Díaz, J Fernando; Altmann, Karl-Heinz; Steinmetz, Michel O
2018-05-29
Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this assay, we have determined the dissociation constants of known maytansine site ligands, including the pharmacologically active degradation product of the clinical antibody-drug conjugate trastuzumab emtansine. In addition, we discovered that the two natural products spongistatin-1 and disorazole Z with established cellular potency bind to the maytansine site on β-tubulin. The high-resolution crystal structures of spongistatin-1 and disorazole Z in complex with tubulin allowed the definition of an additional sub-site adjacent to the pocket shared by all maytansine-site ligands, which could be exploitable as a distinct, separate target site for small molecules. Our study provides a basis for the discovery and development of next-generation MTAs for the treatment of cancer.
NASA Technical Reports Server (NTRS)
Maynard, Nancy G.; Yurchak, Boris; Turi, Johan Mathis; Mathiesen, Svein D.; Aissi-Wespi, Rita L.
2004-01-01
As scientists and policy-makers from both indigenous and non-indigenous communities begin to build closer partnerships to address common sustainability issues such as the health impacts of climate change and anthropogenic activities, it becomes increasingly important to create shared information management systems which integrate all relevant factors for optimal information sharing and decision-making. This paper describes a new GIs-based system being designed to bring local and indigenous traditional knowledge together with scientific data and information, remote sensing, and information technologies to address health-related environment, weather, climate, pollution and land use change issues for improved decision/policy-making for reindeer husbandry. The system is building an easily-accessible archive of relevant current and historical, traditional, local and remotely-sensed and other data and observations for shared analysis, measuring, and monitoring parameters of interest. Protection of indigenous culturally sensitive information will be respected through appropriate data protocols. A mechanism which enables easy information sharing among all participants, which is real time and geo-referenced and which allows interconnectivity with remote sites is also being designed into the system for maximum communication among partners. A preliminary version of our system will be described for a Russian reindeer test site, which will include a combination of indigenous knowledge about local conditions and issues, remote sensing and ground-based data on such parameters as the vegetation state and distribution, snow cover, temperature, ice condition, and infrastructure.
Conceptual Questions and Challenge Problems
NASA Astrophysics Data System (ADS)
Nurrenbern, Susan C.; Robinson, William R.
1998-11-01
The JCE Internet Conceptual Question and Challenge Problem Web site is a source of questions and problems that can be used in teaching and assessing conceptual understanding and problem solving in chemistry. Here you can find a library of free-response and multiple-choice conceptual questions and challenge problems, tips for writing these questions and problems, and a discussion of types of conceptual questions. This site is intended to be a means of sharing conceptual questions and challenge problems among chemical educators. This is a living site that will grow as you share conceptual questions and challenge problems and as we find new sources of information. We would like to make this site as inclusive as possible. Please share your questions and problems with us and alert us to references or Web sites that could be included on the site. You can use email, fax, or regular mail. Email: nurrenbern@purdue.edu or wrrobin@purdue.edu Fax: 765/494-0239 Mailing address: Susan C. Nurrenbern or William R. Robinson; Department of Chemistry; Purdue University; 1393 Brown Building; West Lafayette, IN 47907-1393. The Conceptual Questions and Challenge Problems Web site can be found here.
Daniel, Bastian; Wallner, Silvia; Steiner, Barbara; Oberdorfer, Gustav; Kumar, Prashant; van der Graaff, Eric; Roitsch, Thomas; Sensen, Christoph W; Gruber, Karl; Macheroux, Peter
2016-01-01
Berberine bridge enzyme-like (BBE-like) proteins form a multigene family (pfam 08031), which is present in plants, fungi and bacteria. They adopt the vanillyl alcohol-oxidase fold and predominantly show bi-covalent tethering of the FAD cofactor to a cysteine and histidine residue, respectively. The Arabidopsis thaliana genome was recently shown to contain genes coding for 28 BBE-like proteins, while featuring four distinct active site compositions. We determined the structure of a member of the AtBBE-like protein family (termed AtBBE-like 28), which has an active site composition that has not been structurally and biochemically characterized thus far. The most salient and distinguishing features of the active site found in AtBBE-like 28 are a mono-covalent linkage of a histidine to the 8α-position of the flavin-isoalloxazine ring and the lack of a second covalent linkage to the 6-position, owing to the replacement of a cysteine with a histidine. In addition, the structure reveals the interaction of a glutamic acid (Glu426) with an aspartic acid (Asp369) at the active site, which appear to share a proton. This arrangement leads to the delocalization of a negative charge at the active site that may be exploited for catalysis. The structure also indicates a shift of the position of the isoalloxazine ring in comparison to other members of the BBE-like family. The dioxygen surrogate chloride was found near the C(4a) position of the isoalloxazine ring in the oxygen pocket, pointing to a rapid reoxidation of reduced enzyme by dioxygen. A T-DNA insertional mutant line for AtBBE-like 28 results in a phenotype, that is characterized by reduced biomass and lower salt stress tolerance. Multiple sequence analysis showed that the active site composition found in AtBBE-like 28 is only present in the Brassicaceae, suggesting that it plays a specific role in the metabolism of this plant family.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-22
... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-82,253] Cardinal Health, Financial Shared Services West, Including On- Site Leased Workers From Aerotek, eXcel Staffing, Experis Finance (Manpower), Ricoh, USA, Dawson Creative, Mergis Group and Tailored Management, Albuquerque, NM; Amended Certification Regarding Eligibility To...
2004-02-19
KENNEDY SPACE CENTER, FLA. - KSC Director Jim Kennedy (center) makes a presentation to NASA and other officials about the benefits of locating NASA’s new Shared Services Center in the Central Florida Research Park, near Orlando. Central Florida leaders are proposing the research park as the site for the NASA Shared Services Center. The center would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
Structure and activation of pro-activin A
Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko
2016-01-01
Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274
Rating knowledge sharing in cross-domain collaborative filtering.
Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi
2015-05-01
Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.
Tran, Phong D.; Tran, Thu V.; Orio, Maylis; Torelli, Stephane; Truong, Quang Duc; Nayuki, Keiichiro; Sasaki, Yoshikazu; Chiam, Sing Yang; Yi, Ren; Honma, Itaru; Barber, James; Artero, Vincent
2017-01-01
Molybdenum sulfides are very attractive noble-metal free electrocatalysts for the hydrogen evolution reaction (HER) from water. Atomic structure and identity of the catalytically active sites have been well established for crystalline molybdenum disulfide (c-MoS2) but not for amorphous molybdenum sulfide (a-MoSx) which displays significantly higher HER activity compared to its crystalline counterpart. Here we show that HER–active a-MoSx, prepared either as nanoparticles or as films, is a molecular–based coordination polymer consisting of discrete [Mo3S13]2– building blocks. Of the three terminal disulfide (S22–) ligands within these clusters, two are shared to form the polymer chain. The third one remains free and generates molybdenum hydride moieties as the active site under H2 evolution conditions. Such a molecular structure therefore provides a basis for revisiting the mechanism of a-MoSx catalytic activity, as well as explaining some of its special properties such as reductive activation and corrosion. Our findings open up new avenues for the rational optimisation of this HER electrocatalyst as an alternative to platinum. PMID:26974410
Pentalum SpiDAR Deployment at SWiFT FY17.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Westergaard, Carsten; Pol, Suhas; Pereira, Tassia
2016-12-01
The Texas Tech University ( TTU ) research group is actively studying the wake development of wind turbines, as part of developing innovative wake control strategies to improve the performance of wind farms. Recently, the team received a set of five new gro und lidars to perform field measurements at the Sandia National Laboratories SWiFT site. This document describes tests details including configurations, timeframe, hardware, and the required collaboration from the Sandia team. This test plan will facili tate the coordination between both TTU and the Sandia team in terms of site accessibility, staff training, and data sharing to meetmore » the specific objectives of the tests.« less
ERIC Educational Resources Information Center
Fleming, E. Scott
2000-01-01
Examines the concept of shared-use facilities to help financially support and meet the demand for athletic facilities. Shared-use considerations are explored including cost sharing of ongoing operations, aesthetics, locker rooms, support facilities, parking and site access, and building access and security. (GR)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Podzelinska, K.; Latimer, R; Bhattacharya, A
2010-01-01
Chloramphenicol is a halogenated natural product bearing an unusual dichloroacetyl moiety that is critical for its antibiotic activity. The operon for chloramphenicol biosynthesis in Streptomyces venezuelae encodes the chloramphenicol halogenase CmlS, which belongs to the large and diverse family of flavin-dependent halogenases (FDH's). CmlS was previously shown to be essential for the formation of the dichloroacetyl group. Here we report the X-ray crystal structure of CmlS determined at 2.2 {angstrom} resolution, revealing a flavin monooxygenase domain shared by all FDHs, but also a unique 'winged-helix' C-terminal domain that creates a T-shaped tunnel leading to the halogenation active site. Intriguingly, themore » C-terminal tail of this domain blocks access to the halogenation active site, suggesting a structurally dynamic role during catalysis. The halogenation active site is notably nonpolar and shares nearly identical residues with Chondromyces crocatus tyrosyl halogenase (CndH), including the conserved Lys (K71) that forms the reactive chloramine intermediate. The exception is Y350, which could be used to stabilize enolate formation during substrate halogenation. The strictly conserved residue E44, located near the isoalloxazine ring of the bound flavin adenine dinucleotide (FAD) cofactor, is optimally positioned to function as a remote general acid, through a water-mediated proton relay, which could accelerate the reaction of the chloramine intermediate during substrate halogenation, or the oxidation of chloride by the FAD(C4{alpha})-OOH intermediate. Strikingly, the 8{alpha} carbon of the FAD cofactor is observed to be covalently attached to D277 of CmlS, a residue that is highly conserved in the FDH family. In addition to representing a new type of flavin modification, this has intriguing implications for the mechanism of FDHs. Based on the crystal structure and in analogy to known halogenases, we propose a reaction mechanism for CmlS.« less
Knezevic, Irena; Mount, Phil; Clement, Chantal
2016-10-01
This article outlines preliminary findings of a 3-year project that explored on-site food production on institutional properties, primarily healthcare facilities. There are growing pressures on healthcare facilities to improve their food offerings and incorporate food gardens into their health programs. While several healthcare facilities produce food on-site, there are few studies that explore opportunities, capacities, and institutional barriers related to on-site food production. The study employed mixed methods including historical review, case studies, surveys, interviews, pilot garden projects, and Geographic Information System mapping. The number of participating institutions varied by method. Benefits associated with on-site food production can be health, economic, environmental, and social. There are also institutional barriers including administrative roadblocks, perceived obstacles, and the difficulty in quantitatively, measuring the qualitatively documented benefits. The benefits of food gardens far outweigh the challenges. On-site food production has tremendous potential to improve nutrition for staff and patients, offer healing spaces, better connect institutions with the communities in which they are located, and provide the long-professed benefits of gardening for all involved-from therapeutic benefits and outdoor physical activities to developing skills and social relationships in ways that few other activities do. © The Author(s) 2016.
Oeldorf-Hirsch, Anne; High, Andrew C; Christensen, John L
2018-04-23
This study investigates the relationship between sharing tracked mobile health (mHealth) information online, supportive communication, feedback, and health behavior. Based on the Integrated Theory of mHealth, our model asserts that sharing tracked health information on social networking sites benefits users' perceptions of their health because of the supportive communication they gain from members of their online social networks and that the amount of feedback people receive moderates these associations. Users of mHealth apps (N = 511) completed an online survey, and results revealed that both sharing tracked health information and receiving feedback from an online social network were positively associated with supportive communication. Network support both corresponded with improved health behavior and mediated the association between sharing health information and users' health behavior. As users received greater amounts of feedback from their online social networks, however, the association between sharing tracked health information and health behavior decreased. Theoretical implications for sharing tracked health information and practical implications for using mHealth apps are discussed.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-07
... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-73,555] Hewlett-Packard Company Division of Corporate Administration and Shared Services Including On-Site Leased Workers From Manpower and Including Workers Off-Site From Various States in the United States Reporting to Omaha, NE; Including Employees of Hewlett-Packard Company...
It's complicated: Facebook users' political participation in the 2008 election.
Vitak, Jessica; Zube, Paul; Smock, Andrew; Carr, Caleb T; Ellison, Nicole; Lampe, Cliff
2011-03-01
In the 2008 U.S. presidential election, social network sites such as Facebook allowed users to share their political beliefs, support specific candidates, and interact with others on political issues. But do political activities on Facebook affect political participation among young voters, a group traditionally perceived as apathetic in regard to civic engagement? Or do these activities represent another example of feel-good participation that has little real-world impact, a concept often referred to as "slacktivism"? Results from a survey of undergraduate students (N = 683) at a large public university in the Midwestern United States conducted in the month prior to the election found that students tend to engage in lightweight political participation both on Facebook and in other venues. Furthermore, two OLS regressions found that political activity on Facebook (e.g., posting a politically oriented status update, becoming a "fan" of a candidate) is a significant predictor of other forms of political participation (e.g., volunteering for an organizing, signing a paper or online petition), and that a number of factors--including intensity of Facebook use and the political activity users see their friends performing on the site--predict political activity on Facebook. Students' perceptions regarding the appropriateness of political activity on Facebook, as well as the specific kinds of political activities they engaged in and witnessed within the site, were also explored.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Lei
2008-01-01
Open reading frame 11 (ORF11) of Kaposi's sarcoma-associated herpesvirus belongs to a herpesviral homologous protein family shared by some members of the gamma- herpesvirus subfamily. Little is known about this ORF11 homologous protein family. We have characterized an unknown open reading frame, ORF11, located adjacent and in the opposite orientation to a well-characterized viral IL-6 gene. Northern blot analysis reveals that ORF11 is expressed during the KSHV lytic cycle with delayed-early transcription kinetics. We have determined the 5{prime} and 3{prime} untranslated region of the unspliced ORF11 transcript and identified both the transcription start site and the transcription termination site. Coremore » promoter region, representing ORF11 promoter activity, was mapped to a 159nt fragment 5{prime} most proximal to the transcription start site. A functional TATA box was identified in the core promoter region. Interestingly, we found that ORF11 transcriptional activation is not responsive to Rta, the KSHV lytic switch protein. We also discovered that part of the ORF11 promoter region, the 209nt fragment upstream of the transcription start site, was repressed by phorbol esters. Our data help to understand transcription regulation of ORF11 and to elucidate roles of ORF11 in KSHV pathogenesis and life cycle.« less
Owen, R L; Bhalla, D K
1983-10-01
M cells in Peyer's patch follicle epithelium endocytose and transport luminal materials to intraepithelial lymphocytes. We examined (1) enzymatic characteristics of the epithelium covering mouse and rat Peyer's patches by using cytochemical techniques, (2) distribution of lectin-binding sites by peroxidase-labeled lectins, and (3) anionic site distribution by using cationized ferritin to develop a profile of M cell surface properties. Alkaline phosphatase activity resulted in deposits of dense reaction product over follicle surfaces but was markedly reduced over M cells, unlike esterase which formed equivalent or greater product over M cells. Concanavalin A, ricinus communis agglutinin, wheat germ agglutinin and peanut agglutinin reacted equally with M cells and with surrounding enterocytes over follicle surfaces. Cationized ferritin distributed in a random fashion along microvillus membranes of both M cells and enterocytes, indicating equivalent anionic site distribution. Staining for alkaline phosphatase activity provides a new approach for distinguishing M cells from enterocytes at the light microscopic level. Identical binding of lectins indicates that M cells and enterocytes share common glycoconjugates even though molecular groupings may differ. Lectin binding and anionic charge similarities of M cells and enterocytes may facilitate antigen sampling by M cells of particles and compounds that adhere to intestinal surfaces in non-Peyer's patch areas.
Two billion years of magmatism recorded from a single Mars meteorite ejection site
Lapen, Thomas J.; Righter, Minako; Andreasen, Rasmus; Irving, Anthony J.; Satkoski, Aaron M.; Beard, Brian L.; Nishiizumi, Kunihiko; Jull, A. J. Timothy; Caffee, Marc W.
2017-01-01
The timing and nature of igneous activity recorded at a single Mars ejection site can be determined from the isotope analyses of Martian meteorites. Northwest Africa (NWA) 7635 has an Sm-Nd crystallization age of 2.403 ± 0.140 billion years, and isotope data indicate that it is derived from an incompatible trace element–depleted mantle source similar to that which produced a geochemically distinct group of 327- to 574-million-year-old “depleted” shergottites. Cosmogenic nuclide data demonstrate that NWA 7635 was ejected from Mars 1.1 million years ago (Ma), as were at least 10 other depleted shergottites. The shared ejection age is consistent with a common ejection site for these meteorites. The spatial association of 327- to 2403-Ma depleted shergottites indicates >2 billion years of magmatism from a long-lived and geochemically distinct volcanic center near the ejection site. PMID:28164153
Army Social Media: Harnessing the Power of Networked Communications
2011-09-01
Social Networking : – Facebook – MySpace – Friendster 9/1/2011 Content sharing: -You Tube -Flickr -Vimeo -Photobucket Collaborating/ knowledge...Americans use social media tools and Web sites monthly Social networking is now the #1 activity on the web • Twitter: 54 Million users • Facebook ...anyone you don’t know on Facebook or social networking platforms -Don’t post deployment information, when you’re going on vacation or when
Location of Shared Services, Part Three, Final Report for Phase I, Rural Shared Services.
ERIC Educational Resources Information Center
Northern Montana Coll., Havre.
Part Three of a four-part report, designed to identify, evaluate, and synthesize shared services research and development efforts conducted throughout the nation, identifies 215 sites in 48 states which exhibit potentially significant attempts to improve rural education through some method of sharing services. A brief resume of each of the…
2011-04-20
car - sharing vehicles on-site or within walking distance of BRAC 133,” as there currently is one ZipCar®. Second, the Transportation Coordinator will...for obtaining additional car - sharing vehicles on-site or within walking distance of BRAC 133,” as there currently is one ZipCar® located at 2001 N
User-Centric Secure Cross-Site Interaction Framework for Online Social Networking Services
ERIC Educational Resources Information Center
Ko, Moo Nam
2011-01-01
Social networking service is one of major technological phenomena on Web 2.0. Hundreds of millions of users are posting message, photos, and videos on their profiles and interacting with other users, but the sharing and interaction are limited within the same social networking site. Although users can share some content on a social networking site…
ERIC Educational Resources Information Center
Ball, Albert L.
2012-01-01
Although reports of identity theft continue to be widely published, users continue to post an increasing amount of personal information online, especially within social networking sites (SNS) and e-learning systems (ELS). Research has suggested that many users lack awareness of the threats that risky online personal information sharing poses to…
Manzoor, Farkhanda; Pervez, Mahnoor
2016-12-01
Baiting systems have been introduced using slow-acting bait toxicants to provide environment-friendly and target-specific termite management. In the present study, the Exterra termite bait system (USA) with chlorfluazuron, a chitin synthesis inhibitor, as the active ingredient was tested against termite colonies. Ten residential areas of Lahore, infested with subterranean termites were selected for the study. The study period was from 2013 to 2015. In-ground stations were installed at 10 sites and above-ground stations were only installed at four test sites. Requiem termite bait was prepared according to the label instructions. Results showed that the range of termite activity was between 30 and 214 d to first termite activity on underground monitors with a mean of 78.23 ± 6.44. Timeline graphs also show activity of termites and active ingredient placement for each of the stations at each site. As termite feeding activity in the stations increased, there was a decrease in termite activities in wooden structures, followed by cessation of termite feeding and foraging activity noted in the building structures. It was concluded that a termite baiting system in Pakistan has the potential to suppress and reduce termite populations, when foraging termites feed on the active ingredient and share with nest mates through trophallaxis by installing more bait stations and prolonging baiting period. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Teachers' perspectives of why and how they use the resources of informal science education sites
NASA Astrophysics Data System (ADS)
Youker, Christian Rene
There has been a growing interest in fostering increased connections between schools and community resources---such as informal science sites. This is due, in part, to the recognition that museum learning has many potential advantages, including improving motivation and attitudes, and nurturing curiosity. Some teachers are using the resources of informal science sites more than others. The purpose of this study was to determine why and how some teachers have continually used the resources of informal science education sites. The study was situated within a constructivist paradigm and employed a naturalistic inquiry strategy. Emergent interviews were conducted with six elementary teachers who regularly used the resources of informal science sites. Observations of informal science use and relevant documents were also used in data analysis. Using a qualitative data analysis program, data were unitized, coded and emergent themes were identified. Findings indicated that the teachers shared many characteristics in terms of why they used informal science, and they situated this within the context of their approaches to science teaching. Yet they valued different aspects of informal science as a resource. Support, especially emotional and social support, for using informal science was also important to these teachers, although where this support came from differed among them. All of the teachers had a strong interest in science, were leaders in science education on many levels and tended to seek out science-related projects and activities. While they shared many characteristics in terms of their approach to science teaching, there was great variation in how these teachers used informal science sites and in the amount and kind of support they received. These findings support the notion that there may be many definitions of the effective use of informal science by elementary teachers.
Changing knowledge and beliefs through an oral health pregnancy message.
Bates, S Brady; Riedy, Christine A
2012-01-01
Pregnancy can be a critical and important period in which to intervene to improve oral health in both the mother and her child. This study examined an online approach for promoting awareness of oral health messages targeted at pregnant women, and whether this type of health messaging impacts oral health knowledge and beliefs. The study was conducted in three parts: production and pilot testing of a brief commercial, Web site/commercial launch and testing, and dissemination and monitoring of the commercial on a video-sharing site. The brief commercial and pre- and postsurveys were produced and pilot tested among a convenience sample of pregnant women (n = 13). The revised commercial and surveys were launched on a newly created Web site and monitored for activity. After 2 months, the commercial was uploaded to a popular video-sharing Web site. Fifty-five individuals completed both the pre- and postsurveys after the Web site was launched. No one responded 100 percent correctly on the presurvey; 77.4 percent responded correctly about dental visits during pregnancy, 66.0 percent about cavity prevention, and 50.9 percent about transmission of bacteria by saliva. Most respondents recalled the correct information on the posttest; 100 percent or close to 100 percent accurately responded about visiting the dentist during pregnancy and preventing cavities, while 79.2 percent responded correctly to the transmission question. Social media can effectively provide dental health messages during pregnancy. This approach can play an important role in increasing awareness and improving oral health of both mother and child. © 2011 American Association of Public Health Dentistry.
Camp, Cameron J; Lee, Michelle M
2011-12-12
Montessori-based activities for persons with dementia have been used to successfully provide opportunities for programming between older adults and preschool children in shared site. intergenerational care programs. Such intergenerational programming allows older adults with dementia to fulfill roles of teacher or mentor to younger children or as collaborative workmates for persons with more advanced dementia while providing children with positive one-on-one interactions with older adults. We review several studies using this approach, describe characteristics of the programs, participants and results obtained and provide recommendations for those interested in extending this line of work.
NASA Astrophysics Data System (ADS)
Park, Bong-Won; Lee, Kun Chang
Recent surge of social networking websites in the world supports a widely accepted assumption that people aspires to be recognized online by sharing information with others, perceive enjoyment and keeps to use their social networking site continuously. Different from traditional social networking sites (SNSs) like Cyworld and Facebook, Twitter is famous for its short message and ease of sharing knowledge with others in a prompt manner. Therefore, Twitter is preferred most by many people who seem innovative generically. In this sense, Twitter accumulates its fame as the most influential SNS media among users. However, there is no study to investigate why people holds continuous intention to use the Twitter from the perspective of knowledge-sharing and social presence. To resolve this research issue, this paper adopts six constructs such as personal innovativeness, knowledge-sharing intention, perceived ease of use, perceived enjoyment, social presence, and intention to continuously use. Empirical results with 105 valid questionnaires revealed that the proposed research model is statistically significant, and people's intention to use the Twitter continuously is influenced by social presence, perceived enjoyment, and perceived ease of use.
Barnett, Stephen; Jones, Sandra C; Caton, Tim; Iverson, Don; Bennett, Sue; Robinson, Laura
2014-03-12
GP training in Australia can be professionally isolating, with trainees spread across large geographic areas, leading to problems with rural workforce retention. Virtual communities of practice (VCoPs) may provide a way of improving knowledge sharing and thus reducing professional isolation. The goal of our study was to review the usefulness of a 7-step framework for implementing a VCoP for general practitioner (GP) training and then evaluated the usefulness of the resulting VCoP in facilitating knowledge sharing and reducing professional isolation. The case was set in an Australian general practice training region involving 55 first-term trainees (GPT1s), from January to July 2012. ConnectGPR was a secure, online community site that included standard community options such as discussion forums, blogs, newsletter broadcasts, webchats, and photo sharing. A mixed-methods case study methodology was used. Results are presented and interpreted for each step of the VCoP 7-step framework and then in terms of the outcomes of knowledge sharing and overcoming isolation. Step 1, Facilitation: Regular, personal facilitation by a group of GP trainers with a co-ordinating facilitator was an important factor in the success of ConnectGPR. Step 2, Champion and Support: Leadership and stakeholder engagement were vital. Further benefits are possible if the site is recognized as contributing to training time. Step 3, Clear Goals: Clear goals of facilitating knowledge sharing and improving connectedness helped to keep the site discussions focused. Step 4, A Broad Church: The ConnectGPR community was too narrow, focusing only on first-term trainees (GPT1s). Ideally there should be more involvement of senior trainees, trainers, and specialists. Step 5, A Supportive Environment: Facilitators maintained community standards and encouraged participation. Step 6, Measurement Benchmarking and Feedback: Site activity was primarily driven by centrally generated newsletter feedback. Viewing comments by other participants helped users benchmark their own knowledge, particularly around applying guidelines. Step 7, Technology and Community: All the community tools were useful, but chat was limited and users suggested webinars in future. A larger user base and more training may also be helpful. Time is a common barrier. Trust can be built online, which may have benefit for trainees that cannot attend face-to-face workshops. Knowledge sharing and isolation outcomes: 28/34 (82%) of the eligible GPT1s enrolled on ConnectGPR. Trainees shared knowledge through online chat, forums, and shared photos. In terms of knowledge needs, GPT1s rated their need for cardiovascular knowledge more highly than supervisors. Isolation was a common theme among interview respondents, and ConnectGPR users felt more supported in their general practice (13/14, 92.9%). The 7-step framework for implementation of an online community was useful. Overcoming isolation and improving connectedness through an online knowledge sharing community shows promise in GP training. Time and technology are barriers that may be overcome by training, technology, and valuable content. In a VCoP, trust can be built online. This has implications for course delivery, particularly in regional areas. VCoPs may also have a specific role assisting overseas trained doctors to interpret their medical knowledge in a new context.
Role of Bassoon and Piccolo in Assembly and Molecular Organization of the Active Zone
Gundelfinger, Eckart D.; Reissner, Carsten; Garner, Craig C.
2016-01-01
Bassoon and Piccolo are two very large scaffolding proteins of the cytomatrix assembled at the active zone (CAZ) where neurotransmitter is released. They share regions of high sequence similarity distributed along their entire length and seem to share both overlapping and distinct functions in organizing the CAZ. Here, we survey our present knowledge on protein-protein interactions and recent progress in understanding of molecular functions of these two giant proteins. These include roles in the assembly of active zones (AZ), the localization of voltage-gated Ca2+ channels (VGCCs) in the vicinity of release sites, synaptic vesicle (SV) priming and in the case of Piccolo, a role in the dynamic assembly of the actin cytoskeleton. Piccolo and Bassoon are also important for the maintenance of presynaptic structure and function, as well as for the assembly of CAZ specializations such as synaptic ribbons. Recent findings suggest that they are also involved in the regulation activity-dependent communication between presynaptic boutons and the neuronal nucleus. Together these observations suggest that Bassoon and Piccolo use their modular structure to organize super-molecular complexes essential for various aspects of presynaptic function. PMID:26793095
Tamara Heartsill Scalley; Saara DeWalt; François Korysko; Guy Van Laere; Kasey Jacobs; Seth Panka; Joseph Torres
2016-01-01
We presented a new information-sharing platform at the 16th Caribbean Foresters Meeting in August 2013 to facilitate and promote collaboration among Caribbean foresters. The platform can be accessed through the Caribbean Foresters website where information and data on forest research sites can be shared. There is a special focus on identifying potential collaborations...
Xu, Yingying; Lee, Jinhyuk; Lü, Zhi-Rong; Mu, Hang; Zhang, Qian; Park, Yong-Doo
2016-07-01
Understanding the mechanism of acetaldehyde dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea-mediated unfolding of ALDH1 and the catalytic role associated with conformational changes.
Establishment of a Multi-State Experiential Pharmacy Program Consortium
Unterwagner, Whitney L.; Byrd, Debbie C.
2008-01-01
In 2002, a regional consortium was created for schools and colleges of pharmacy in Georgia and Alabama to assist experiential education faculty and staff members in streamlining administrative processes, providing required preceptor development, establishing a professional network, and conducting scholarly endeavors. Five schools and colleges of pharmacy with many shared experiential practice sites formed a consortium to help experiential faculty and staff members identify, discuss, and solve common experience program issues and challenges. During its 5 years in existence, the Southeastern Pharmacy Experiential Education Consortium has coordinated experiential schedules, developed and implemented uniform evaluation tools, coordinated site and preceptor development activities, established a work group for educational research and scholarship, and provided opportunities for networking and professional development. Several consortium members have received national recognition for their individual experiential education accomplishments. Through the activities of a regional consortium, members have successfully developed programs and initiatives that have streamlined administrative processes and have the potential to improve overall quality of experiential education programs. Professionally, consortium activities have resulted in 5 national presentations. PMID:18698386
Ding, Weimin; Sun, Miao; Luo, Shaman; Xu, Tao; Cao, Yibo; Yan, Xiufeng; Wang, Yang
2013-08-22
Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) in the outer bark of birch trees, and shares the same pentacyclic triterpenoid core as BA, yet exhibits no significant cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives and their in vitro anti-cancer activity results (reported as IC₅₀ values) against HT29 human colon cancer cells in the present study. All derivatives share a common pentacyclic triterpenoid core and the molecules were split into three pieces by cutting at the C-3 and C-28 sites with a consideration toward structural diversity. The analysis gave a leave-one-out cross-validation q² value of 0.722 and a non-cross-validation r² value of 0.974, which suggested that the model has good predictive ability (q² > 0.2). The contour maps illustrated that bulky and electron-donating groups would be favorable for activity at the C-28 site, and a moderately bulky and electron-withdrawing group near the C-3 site would improve this activity. BE derivatives were designed and synthesized according to the modeling result, whereby bulky electronegative groups (maleyl, phthalyl, and hexahydrophthalyl groups) were directly introduced at the C-28 position of BE. The in vitro cytotoxicity values of the given analogs against HT29 cells were consistent with the predicted values, proving that the present topomer CoMFA model is successful and that it could potentially guide the synthesis of new betulinic acid derivatives with high anti-cancer activity. The IC₅₀ values of these three new compounds were also assayed in five other tumor cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer activities and its IC₅₀ values were lower than those of BA in all cell lines, excluding DU145 cells.
Quality improvement project to reduce infiltration and extravasation events in a pediatric hospital.
Tofani, Barbara F; Rineair, Sylvia A; Gosdin, Craig H; Pilcher, Patricia M; McGee, Susan; Varadarajan, Kartik R; Schoettker, Pamela J
2012-12-01
A safety event response team at Cincinnati Children's Hospital Medical Center developed and tested improvement strategies to reduce peripheral intravenous (PIV) infiltration and extravasation injuries. Improvement activities included development of the touch-look-compare method for hourly PIV site assessment, staff education and mandatory demonstration of PIV site assessment, and performance monitoring and sharing of compliance results. We observed a significant reduction in the injury rate immediately following implementation of the interventions that corresponded with monitoring compliance in performing hourly assessments on patients with a PIV, but this was not sustained. The team is currently examining other strategies to reduce PIV injuries. Copyright © 2012 Elsevier Inc. All rights reserved.
Proton Transfer in the Catalytic Cycle of [NiFe] Hydrogenases: Insight from Vibrational Spectroscopy
2017-01-01
Catalysis of H2 production and oxidation reactions is critical in renewable energy systems based around H2 as a clean fuel, but the present reliance on platinum-based catalysts is not sustainable. In nature, H2 is oxidized at minimal overpotential and high turnover frequencies at [NiFe] catalytic sites in hydrogenase enzymes. Although an outline mechanism has been established for the [NiFe] hydrogenases involving heterolytic cleavage of H2 followed by a first and then second transfer of a proton and electron away from the active site, details remain vague concerning how the proton transfers are facilitated by the protein environment close to the active site. Furthermore, although [NiFe] hydrogenases from different organisms or cellular environments share a common active site, they exhibit a broad range of catalytic characteristics indicating the importance of subtle changes in the surrounding protein in controlling their behavior. Here we review recent time-resolved infrared (IR) spectroscopic studies and IR spectroelectrochemical studies carried out in situ during electrocatalytic turnover. Additionally, we re-evaluate the significant body of IR spectroscopic data on hydrogenase active site states determined through more conventional solution studies, in order to highlight mechanistic steps that seem to apply generally across the [NiFe] hydrogenases, as well as steps which so far seem limited to specific groups of these enzymes. This analysis is intended to help focus attention on the key open questions where further work is needed to assess important aspects of proton and electron transfer in the mechanism of [NiFe] hydrogenases. PMID:28413691
Horowitz, Scott; Dirk, Lynnette M A; Yesselman, Joseph D; Nimtz, Jennifer S; Adhikari, Upendra; Mehl, Ryan A; Scheiner, Steve; Houtz, Robert L; Al-Hashimi, Hashim M; Trievel, Raymond C
2013-10-16
S-adenosylmethionine (AdoMet)-based methylation is integral to metabolism and signaling. AdoMet-dependent methyltransferases belong to multiple distinct classes and share a catalytic mechanism that arose through convergent evolution; however, fundamental determinants underlying this shared methyl transfer mechanism remain undefined. A survey of high-resolution crystal structures reveals that unconventional carbon-oxygen (CH···O) hydrogen bonds coordinate the AdoMet methyl group in different methyltransferases irrespective of their class, active site structure, or cofactor binding conformation. Corroborating these observations, quantum chemistry calculations demonstrate that these charged interactions formed by the AdoMet sulfonium cation are stronger than typical CH···O hydrogen bonds. Biochemical and structural studies using a model lysine methyltransferase and an active site mutant that abolishes CH···O hydrogen bonding to AdoMet illustrate that these interactions are important for high-affinity AdoMet binding and transition-state stabilization. Further, crystallographic and NMR dynamics experiments of the wild-type enzyme demonstrate that the CH···O hydrogen bonds constrain the motion of the AdoMet methyl group, potentially facilitating its alignment during catalysis. Collectively, the experimental findings with the model methyltransferase and structural survey imply that methyl CH···O hydrogen bonding represents a convergent evolutionary feature of AdoMet-dependent methyltransferases, mediating a universal mechanism for methyl transfer.
Kinetic and Spectroscopic Studies of Bicupin Oxalate Oxidase and Putative Active Site Mutants
Moomaw, Ellen W.; Hoffer, Eric; Moussatche, Patricia; Salerno, John C.; Grant, Morgan; Immelman, Bridget; Uberto, Richard; Ozarowski, Andrew; Angerhofer, Alexander
2013-01-01
Ceriporiopsis subvermispora oxalate oxidase (CsOxOx) is the first bicupin enzyme identified that catalyzes manganese-dependent oxidation of oxalate. In previous work, we have shown that the dominant contribution to catalysis comes from the monoprotonated form of oxalate binding to a form of the enzyme in which an active site carboxylic acid residue must be unprotonated. CsOxOx shares greatest sequence homology with bicupin microbial oxalate decarboxylases (OxDC) and the 241-244DASN region of the N-terminal Mn binding domain of CsOxOx is analogous to the lid region of OxDC that has been shown to determine reaction specificity. We have prepared a series of CsOxOx mutants to probe this region and to identify the carboxylate residue implicated in catalysis. The pH profile of the D241A CsOxOx mutant suggests that the protonation state of aspartic acid 241 is mechanistically significant and that catalysis takes place at the N-terminal Mn binding site. The observation that the D241S CsOxOx mutation eliminates Mn binding to both the N- and C- terminal Mn binding sites suggests that both sites must be intact for Mn incorporation into either site. The introduction of a proton donor into the N-terminal Mn binding site (CsOxOx A242E mutant) does not affect reaction specificity. Mutation of conserved arginine residues further support that catalysis takes place at the N-terminal Mn binding site and that both sites must be intact for Mn incorporation into either site. PMID:23469254
Increasing the structural coverage of tuberculosis drug targets.
Baugh, Loren; Phan, Isabelle; Begley, Darren W; Clifton, Matthew C; Armour, Brianna; Dranow, David M; Taylor, Brandy M; Muruthi, Marvin M; Abendroth, Jan; Fairman, James W; Fox, David; Dieterich, Shellie H; Staker, Bart L; Gardberg, Anna S; Choi, Ryan; Hewitt, Stephen N; Napuli, Alberto J; Myers, Janette; Barrett, Lynn K; Zhang, Yang; Ferrell, Micah; Mundt, Elizabeth; Thompkins, Katie; Tran, Ngoc; Lyons-Abbott, Sally; Abramov, Ariel; Sekar, Aarthi; Serbzhinskiy, Dmitri; Lorimer, Don; Buchko, Garry W; Stacy, Robin; Stewart, Lance J; Edwards, Thomas E; Van Voorhis, Wesley C; Myler, Peter J
2015-03-01
High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.
Increasing the structural coverage of tuberculosis drug targets
DOE Office of Scientific and Technical Information (OSTI.GOV)
Baugh, Loren; Phan, Isabelle; Begley, Darren W.
High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. We found that of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structuresmore » would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PS APF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.« less
Increasing the structural coverage of tuberculosis drug targets
Baugh, Loren; Phan, Isabelle; Begley, Darren W.; ...
2014-12-19
High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. We found that of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structuresmore » would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PS APF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.« less
Peng, Dungeng; Satterlee, James D.; Ma, Li-Hua; Dallas, Jerry L.; Smith, Kevin M.; Zhang, Xuhong; Sato, Michihiko; La Mar, Gerd N.
2011-01-01
Heme oxygenase, HO, from the pathogenic bacterium N. meningitidis, NmHO, which secures host iron, shares many properties with mammalian HOs, but also exhibits some key differences. The crystal structure appears more compact and the crystal-undetected C-terminus interacts with substrate in solution. The unique nature of substrate-protein, specifically pyrrole-I/II-helix-2, peripheral interactions in NmHO are probed by 2D 1H NMR to reveal unique structural features controlling substrate orientation. The thermodynamics of substrate orientational isomerism are mapped for substrates with individual vinyl → methyl → hydrogen substitutions and with enzyme C-terminal deletions. NmHO exhibits significantly stronger orientational preference, reflecting much stronger and selective pyrrole-I/II interactions with the protein matrix, than in mammalian HOs. Thus, replacing bulky vinyls with hydrogens results in a 180° rotation of substrate about the α,γ-meso axis in the active site. A "collapse" of the substrate pocket as substrate size decreases is reflected in movement of helix-2 toward the substrate as indicated by significant and selective increased NOESY cross peak intensity, increase in steric Fe-CN tilt reflected in the orientation of the major magnetic axis, and decrease in steric constraints controlling the rate of aromatic ring reorientation. The active site of NmHO appears "stressed" for native protohemin and its "collapse" upon replacing vinyls by hydrogen leads to a factor ~102 increase in substrate affinity. Interaction of the C-terminus with the active site destabilizes the crystallographic protohemin orientation by ~0.7 kcal/mol, which is consistent with optimizing the His207-Asp27 H-bond. Implications of the active site "stress" for product release are discussed. PMID:21870860
Increasing the Structural Coverage of Tuberculosis Drug Targets
Baugh, Loren; Phan, Isabelle; Begley, Darren W.; Clifton, Matthew C.; Armour, Brianna; Dranow, David M.; Taylor, Brandy M.; Muruthi, Marvin M.; Abendroth, Jan; Fairman, James W.; Fox, David; Dieterich, Shellie H.; Staker, Bart L.; Gardberg, Anna S.; Choi, Ryan; Hewitt, Stephen N.; Napuli, Alberto J.; Myers, Janette; Barrett, Lynn K.; Zhang, Yang; Ferrell, Micah; Mundt, Elizabeth; Thompkins, Katie; Tran, Ngoc; Lyons-Abbott, Sally; Abramov, Ariel; Sekar, Aarthi; Serbzhinskiy, Dmitri; Lorimer, Don; Buchko, Garry W.; Stacy, Robin; Stewart, Lance J.; Edwards, Thomas E.; Van Voorhis, Wesley C.; Myler, Peter J.
2015-01-01
High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1Å, >85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases. PMID:25613812
Analysis of the YouTube videos on basic life support and cardiopulmonary resuscitation.
Tourinho, Francis Solange Vieira; de Medeiros, Kleyton Santos; Salvador, Pétala Tuani Candido De Oliveira; Castro, Grayce Loyse Tinoco; Santos, Viviane Euzébia Pereira
2012-01-01
To analyze the videos on the YouTube video sharing site, noting which points addressed in the videos related to CPR and BLS, based on the 2010 Guidelines for the American Heart Association (AHA). This was an exploratory, quantitative and qualitative research performed in the YouTube sharing site, using as keywords the expressions in Portuguese equivalent to the Medical Subject Headings (MeSH) "Cardiopulmonary Resuscitation" and "Basic Life Support" for videos that focused on the basic life support. The research totaled 260 videos over the two searches. Following the exclusion criteria, 61 videos remained. These mostly are posted by individuals and belong to the category Education. Moreover, most of the videos, despite being added to the site after the publication of the 2010 AHA Guidelines, were under the older 2005 guidelines. Although the video-sharing site YouTube is widely used today, it lacks videos about CPR and BLS that comply to the most recent AHA recommendations, which may negatively influence the population that uses it.
Dong, Dong; Ako, Roland; Hu, Ming; Wu, Baojian
2015-01-01
The UDP-glucuronosyltransferase (UGT) enzyme catalyzes the glucuronidation reaction which is a major metabolic and detoxification pathway in humans. Understanding the mechanisms for substrate recognition by UGT assumes great importance in an attempt to predict its contribution to xenobiotic/drug disposition in vivo. Spurred on by this interest, 2D/3D-quantitative structure activity relationships (QSAR) and pharmacophore models have been established in the absence of a complete mammalian UGT crystal structure. This review discusses the recent progress in modeling human UGT substrates including those with multiple sites of glucuronidation. A better understanding of UGT active site contributing to substrate selectivity (and regioselectivity) from the homologous enzymes (i.e., plant and bacterial UGTs, all belong to family 1 of glycosyltransferase (GT1)) is also highlighted, as these enzymes share a common catalytic mechanism and/or overlapping substrate selectivity. PMID:22385482
Galaxy Zoo: An Experiment in Public Science Participation
NASA Astrophysics Data System (ADS)
Raddick, Jordan; Lintott, C. J.; Schawinski, K.; Thomas, D.; Nichol, R. C.; Andreescu, D.; Bamford, S.; Land, K. R.; Murray, P.; Slosar, A.; Szalay, A. S.; Vandenberg, J.; Galaxy Zoo Team
2007-12-01
An interesting question in modern astrophysics research is the relationship between a galaxy's morphology (appearance) and its formation and evolutionary history. Research into this question is complicated by the fact that to get a study sample, researchers must first assign a shape to a large number of galaxies. Classifying a galaxy by shape is nearly impossible for a computer, but easy for a human - however, looking at one million galaxies, one at a time, would take an enormous amount of time. To create such a research sample, we turned to citizen science. We created a web site called Galaxy Zoo (www.galaxyzoo.org) that invites the public to classify the galaxies. New members see a short tutorial and take a short skill test where they classify galaxies of known types. Once they pass the test, they begin to work with the entire sample. The site's interface shows the user an image of a single galaxy from the Sloan Digital Sky Survey. The user clicks a button to classify it. Each classification is stored in a database, associated with the galaxy that it describes. The site has become enormously popular with amateur astronomers, teachers, and others interested in astronomy. So far, more than 110,000 users have joined. We have started a forum where users share images of their favorite galaxies, ask science questions of each other and the "zookeepers," and share classification advice. In a separate poster, we will share science results from the site's first six months of operation. In this poster, we will describe the site as an experiment in public science outreach. We will share user feedback, discuss our plans to study the user community more systematically, and share advice on how to work with citizen science projects to the mutual benefit of both professional and citizen scientists.
An i2b2-based, generalizable, open source, self-scaling chronic disease registry
Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D
2013-01-01
Objective Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Materials and methods Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. Results The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. Discussion We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. Conclusions The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases. PMID:22733975
An i2b2-based, generalizable, open source, self-scaling chronic disease registry.
Natter, Marc D; Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D
2013-01-01
Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.
NIST Document Sharing Test Facility
NIST Document Sharing Test Facility This site supports the IHE effort in Document Sharing as part . This test facility is based on the IHE IT Infrastructure Technical Framework. All testing done against that Patient IDs be pre-registered before submitting metadata about them. To allocate new patient IDs
The Tensions between Shared Governance and Advancing Educational Equity
ERIC Educational Resources Information Center
Castagno, Angelina E.; Hausman, Charles
2017-01-01
This article examines the relationship between shared governance and one school district's (in)ability to advance educational equity. Specifically, we consider the district's policies, discourse, and practice around equity within the context of site-based management and shared decision making. We suggest that if equity is indeed a major district…
Outcomes of the 'Data Curation for Geobiology at Yellowstone National Park' Workshop
NASA Astrophysics Data System (ADS)
Thomer, A.; Palmer, C. L.; Fouke, B. W.; Rodman, A.; Choudhury, G. S.; Baker, K. S.; Asangba, A. E.; Wickett, K.; DiLauro, T.; Varvel, V.
2013-12-01
The continuing proliferation of geological and biological data generated at scientifically significant sites (such as hot springs, coral reefs, volcanic fields and other unique, data-rich locales) has created a clear need for the curation and active management of these data. However, there has been little exploration of what these curation processes and policies would entail. To that end, the Site-Based Data Curation (SBDC) project is developing a framework of guidelines and processes for the curation of research data generated at scientifically significant sites. A workshop was held in April 2013 at Yellowstone National Park (YNP) to gather input from scientists and stakeholders. Workshop participants included nine researchers actively conducting geobiology research at YNP, and seven YNP representatives, including permitting staff and information professionals from the YNP research library and archive. Researchers came from a range of research areas -- geology, molecular and microbial biology, ecology, environmental engineering, and science education. Through group discussions, breakout sessions and hands-on activities, we sought to generate policy recommendations and curation guidelines for the collection, representation, sharing and quality control of geobiological datasets. We report on key themes that emerged from workshop discussions, including: - participants' broad conceptions of the long-term usefulness, reusability and value of data. - the benefits of aggregating site-specific data in general, and geobiological data in particular. - the importance of capturing a dataset's originating context, and the potential usefulness of photographs as a reliable and easy way of documenting context. - researchers' and resource managers' overlapping priorities with regards to 'big picture' data collection and management in the long-term. Overall, we found that workshop participants were enthusiastic and optimistic about future collaboration and development of community approaches to data sharing. We hope to continue discussion of geobiology data curation challenges and potential strategies at AGU. Outcomes from the workshop are guiding next steps in the SBDC project, led by investigators at the Center for Informatics Research in Science and Scholarship and Institute for Genomic Biology at the University of Illinois, in collaboration with partners at Johns Hopkins University and YNP.
Been, M D; Perrotta, A T
1995-01-01
A non-Watson-Crick G.G interaction within the core region of the hepatitis delta virus (HDV) antigenomic ribozyme is required for optimal rates of self-cleavage activity. Base substitutions for either one or both G's revealed that full activity was obtained only when both G's were replaced with A's. At those positions, substitutions that generate potential Watson-Crick, G.U, heteropurine, or homopyrimidine combinations resulted in dramatically lower cleavage activity. A homopurine symmetric base pair, of the same type identified in the high-affinity binding site of the HIV RRE, is most consistent with this data. Additional features shared between the antigenomic ribozyme and the Rev binding site in the vicinity of the homopurine pairs suggest some structural similarity for this region of the two RNAs and a possible motif associated with this homopurine interaction. Evidence for a homopurine pair at the equivalent position in a modified form of the HDV genomic ribozyme was also found. With the postulated symmetric pairing scheme, large distortions in the nucleotide conformation, the sugar-phosphate backbone, or both would be necessary to accommodate this interaction at the end of a helix; we hypothesize that this distortion is critical to the structure of the active site of the ribozyme and it is stabilized by the homopurine base pair. PMID:8595561
Baby Boomers in an Active Adult Retirement Community: Comity Interrupted
Roth, Erin G.; Keimig, Lynn; Rubinstein, Robert L.; Morgan, Leslie; Eckert, J. Kevin; Goldman, Susan; Peeples, Amanda D.
2012-01-01
Purpose of the Study: This article explores a clash between incoming Baby Boomers and older residents in an active adult retirement community (AARC). We examine issues of social identity and attitudes as these groups encounter each other. Design and Methods: Data are drawn from a multiyear ethnographic study of social relations in senior housing. Research at this site included in-depth, open-ended interviews (47), field notes (25), and participant observation in the field (500 hr). Research team biweekly discussions and Atlas.ti software program facilitated analysis. Findings: We begin with a poignant incident that has continued to engender feelings of rejection by elders with each retelling and suggests the power and prevalence of ageism in this AARC. We identify three pervasive themes: (a) social identity and image matter, (b) significant cultural and attitudinal differences exist between Boomers and older residents, and (c) shared age matters less than shared interests. Implications: Our data clearly show the operation of ageism in this community and an equating of being old with being sick. The conflict between these two age cohorts suggests that cohort consciousness among Boomers carries elements of age denial, shared by the older old. It also challenges the Third Age concept as a generational phenomenon. PMID:22391870
2004-02-19
KENNEDY SPACE CENTER, FLA. - KSC Director Jim Kennedy makes a presentation to NASA and other officials about the benefits of locating NASA’s new Shared Services Center in the Central Florida Research Park, near Orlando. At the far left is Pamella J. Dana, Ph.D., director, Office of Tourism, Trade, and Economic Development in Florida. Central Florida leaders are proposing the research park as the site for the NASA Shared Services Center. The center would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
Hyakutake, Manami; Tomizawa, Satoshi; Mizuno, Kouhei; Hisano, Tamao; Abe, Hideki; Tsuge, Takeharu
2015-06-01
Polyhydroxyalkanoate (PHA) synthase from Bacillus cereus YB-4 (PhaRCYB4) catalyzes not only PHA polymerization but also alcoholytic cleavage of PHA chains. The alcoholysis activity of PhaRCYB4 is expressed when a hydroxyacyl-CoA monomer is absent but an alcohol compound is present. In this study, we performed alanine mutagenesis of the putative catalytic triad (Cys(151), Asp(306), and His(335)) in the PhaCYB4 subunit to identify the active site residues for polymerization and alcoholysis activities. Individual substitution of each triad residue with alanine resulted in loss of both polymerization and alcoholysis activities, suggesting that these residues are commonly shared between polymerization and alcoholysis reactions. The loss of activity was also observed following mutagenesis of the triad to other amino acids, except for one PhaRCYB4 mutant with a C151S substitution, which lost polymerization activity but still possessed cleavage activity towards PHA chains. The low-molecular-weight PHA isolated from the PhaRCYB4(C151S)-expressing strain showed a lower ratio of alcohol capping at the P(3HB) carboxy terminus than did that from the wild-type-expressing strain. This observation implies that hydrolysis activity of PhaRCYB4 might be elicited by the C151S mutation.
Ullah, Riaz; Yasir, Muhammad; Khan, Imran; Bibi, Fehmida; Sohrab, Sayed Sartaj; Al-Ansari, Ahmed; Al-Abbasi, Fahad; Al-Sofyani, Abdulmohsin A; Daur, Ihsanullah; Lee, Seon-Woo; Azhar, Esam I
2017-08-01
Mangrove habitats are ecologically important ecosystems that are under severe pressure worldwide because of environmental changes and human activities. In this study, 16S rRNA gene amplicon deep-sequencing was used to compare bacterial communities in Red Sea mangrove ecosystems at anthropogenically influenced coastal sites with those at a relatively pristine island site. In total, 32 phyla were identified from the mangrove rhizospheres, with Proteobacteria predominating at each of the studied sites; however, the relative abundance was significantly decreased at the coastal sites (Mastorah, MG-MS; Ar-Rayis, MG-AR) compared with the pristine island site near Dhahban (MG-DBI). The phyla Actinobacteria, Firmicutes, Acidobacteria, Chloroflexi, Spirochetes, and Planctomycetes were present at a relative abundance of >1% at the MG-MS and MG-AR sites, but their concentration was <1% at the MG-DBI site. A total of 1659 operational taxonomic units (OTUs) were identified at the species level, and approximately 945 OTUs were shared across the different sampling sites. Multivariate principal coordinate data analysis separated the MG-DBI site from the MG-AR and MG-MS cluster. Specific bacterial taxa were enriched at each location, and in particular, the genera Pseudoalteromonas and Cobetia were predominantly identified in the MG-DBI site compared with the anthropogenically influenced coastal sites.
MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.
Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K
2011-03-01
Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A Molecular Imaging Data Grid design, implementation, and initial evaluation is presented to demonstrate the secure and novel data grid solution for sharing preclinical molecular imaging data across the wide-area-network (WAN).
#LancerHealth: Using Twitter and Instagram as a tool in a campus wide health promotion initiative
Santarossa, Sara; Woodruff, Sarah J.
2018-01-01
The present study aimed to explore using popular technology that people already have/use as a health promotion tool, in a campus wide social media health promotion initiative, entitled #LancerHealth. During a two-week period the university community was asked to share photos on Twitter and Instagram of What does being healthy on campus look like to you?, while tagging the image with #LancerHealth. All publically tagged media was collected using the Netlytic software and analysed. Text analysis (N=234 records, Twitter; N=141 records, Instagram) revealed that the majority of the conversation was positive and focused on health and the university. Social network analysis, based on five network properties, showed a small network with little interaction. Lastly, photo coding analysis (N=71 unique image) indicated that the majority of the shared images were of physical activity (52%) and on campus (80%). Further research into this area is warranted. Significance for public healthAs digital media continues to become a popular tool among both public health organizations and those in academia, it is important to understand how, why, and which platforms individuals are using in regards to their health. This campus wide, social media health promotion initiative found that people will use popular social networking sites like Twitter and Instagram to share their healthy behaviours. Online social networks, created through social networking sites, can play a role in social diffusion of public health information and health behaviours. In this study, however, social network analysis revealed that there needs to be influential and highly connected individuals sharing information to generate social diffusion. This study can help guide future public health research in the area of social media and its potential influence on health promotion. PMID:29780763
Detection of damaged DNA bases by DNA glycosylase enzymes.
Friedman, Joshua I; Stivers, James T
2010-06-22
A fundamental and shared process in all forms of life is the use of DNA glycosylase enzymes to excise rare damaged bases from genomic DNA. Without such enzymes, the highly ordered primary sequences of genes would rapidly deteriorate. Recent structural and biophysical studies are beginning to reveal a fascinating multistep mechanism for damaged base detection that begins with short-range sliding of the glycosylase along the DNA chain in a distinct conformation we call the search complex (SC). Sliding is frequently punctuated by the formation of a transient "interrogation" complex (IC) where the enzyme extrahelically inspects both normal and damaged bases in an exosite pocket that is distant from the active site. When normal bases are presented in the exosite, the IC rapidly collapses back to the SC, while a damaged base will efficiently partition forward into the active site to form the catalytically competent excision complex (EC). Here we review the unique problems associated with enzymatic detection of rare damaged DNA bases in the genome and emphasize how each complex must have specific dynamic properties that are tuned to optimize the rate and efficiency of damage site location.
Transactivation of the proximal promoter of human oxytocin gene by TR4 orphan receptor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, C.-P.; Lee, Y.-F.; Chang, C.
2006-12-08
The human testicular receptor 4 (TR4) shares structural homology with members of the nuclear receptor superfamily. Some other members of this superfamily were able to regulate the transcriptional activity of the human oxytocin (OXT) promoter by binding to the first DR0 regulatory site. However, little investigation was conducted systematically in the study of the second dDR4 site of OXT proximal promoter, and the relationship between the first and the second sites of OXT promoter. Here, we demonstrated for the first time that TR4 could increase the proximal promoter activity of the human OXT gene via DR0, dDR4, and OXT (bothmore » DR0 and dDR4) elements, respectively. TR4 might induce OXT gene expression through the OXT element in a dose-dependent manner. However, there is no synergistic effect between DR0 and dDR4 elements during TR4 transactivation. Taken together, these results suggested that TR4 should be one of important regulators of OXT gene expression.« less
Fanconi Anemia Core Complex Gene Promoters Harbor Conserved Transcription Regulatory Elements
Meier, Daniel; Schindler, Detlev
2011-01-01
The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5′ region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3′ regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters. PMID:21826217
Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.
Meier, Daniel; Schindler, Detlev
2011-01-01
The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.
Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins
Nakai, Shuryo; Li-Chan, Eunice CY; Dou, Jinglie
2005-01-01
Background Although it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within the 3D structures may be needed for functional annotation of protein sequences. Using the approach of quantitative structure-activity relationships (QSAR), we have proposed a new algorithm for postulating functional mechanisms on the basis of pattern similarity and average of property values of side-chains in segments within sequences. This approach was used to search for functional sites of proteins belonging to the lysozyme and cystatin families. Results Hydrophobicity and β-turn propensity of reference segments with 3–7 residues were used for the homology similarity search (HSS) for active sites. Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes. The profiles of similarity constants and average values of these parameters as functions of their positions in the sequences could identify both active and substrate binding sites of the lysozyme of Streptomyces coelicolor, which has been reported as a new fold enzyme (Cellosyl). The same approach was successfully applied to cystatins, especially for postulating the mechanisms of amyloidosis of human cystatin C as well as human lysozyme. Conclusion Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences. This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available. PMID:15904486
Patil, Dipak N.; Datta, Manali; Dev, Aditya; Dhindwal, Sonali; Singh, Nirpendra; Dasauni, Pushpanjali; Kundu, Suman; Sharma, Ashwani K.; Tomar, Shailly; Kumar, Pravindra
2013-01-01
The glycosyl hydrolase 18 (GH18) family consists of active chitinases as well as chitinase like lectins/proteins (CLPs). The CLPs share significant sequence and structural similarities with active chitinases, however, do not display chitinase activity. Some of these proteins are reported to have specific functions and carbohydrate binding property. In the present study, we report a novel chitinase like lectin (TCLL) from Tamarindus indica. The crystal structures of native TCLL and its complex with N-acetyl glucosamine were determined. Similar to the other CLPs of the GH18 members, TCLL lacks chitinase activity due to mutations of key active site residues. Comparison of TCLL with chitinases and other chitin binding CLPs shows that TCLL has substitution of some chitin binding site residues and more open binding cleft due to major differences in the loop region. Interestingly, the biochemical studies suggest that TCLL is an N-acetyl glucosamine specific chi-lectin, which is further confirmed by the complex structure of TCLL with N-acetyl glucosamine complex. TCLL has two distinct N-acetyl glucosamine binding sites S1 and S2 that contain similar polar residues, although interaction pattern with N-acetyl glucosamine varies extensively among them. Moreover, TCLL structure depicts that how plants utilize existing structural scaffolds ingenuously to attain new functions. To date, this is the first structural investigation of a chi-lectin from plants that explore novel carbohydrate binding sites other than chitin binding groove observed in GH18 family members. Consequently, TCLL structure confers evidence for evolutionary link of lectins with chitinases. PMID:23717482
Affording to exchange: social capital and online information sharing.
Maksl, Adam; Young, Rachel
2013-08-01
The potential harm and benefit associated with sharing personal information online is a topic of debate and discussion. Using survey methods (n=872), we explore whether attainment of social capital online relates to greater comfort with sharing personal information. We found that perceptions of bridging and bonding social capital earned from using Facebook are significant predictors of overall comfort levels with sharing personal information. This research raises timely questions about how the perceived benefits of social networking sites influence how personal information is shared online.
NASA Astrophysics Data System (ADS)
Samson, P. J.
2010-12-01
The public is painfully aware when the sky turns murky and air quality advisories are posted. They are often less aware if or how these events are associated with particular weather and airflow conditions. In order to give citizens the power to explore their air quality a web site, SharedAir, has been created that lists concentrations of pollutants at various measurement sites around the world and displays the trajectories associated with each day. This site is a first step in raising public literacy on how atmospheric transport affects air quality degradation. SharedAir representation of sulfate concentrations measured in Sacramento, CA on December 6, 2006.
Sharmin, Refat; Islam, Abul B M M K
2016-01-01
MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein's antigenic sites are found to be conserved with those in HKU4 and HKU5. This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity.
Sharing lattice QCD data over a widely distributed file system
NASA Astrophysics Data System (ADS)
Amagasa, T.; Aoki, S.; Aoki, Y.; Aoyama, T.; Doi, T.; Fukumura, K.; Ishii, N.; Ishikawa, K.-I.; Jitsumoto, H.; Kamano, H.; Konno, Y.; Matsufuru, H.; Mikami, Y.; Miura, K.; Sato, M.; Takeda, S.; Tatebe, O.; Togawa, H.; Ukawa, A.; Ukita, N.; Watanabe, Y.; Yamazaki, T.; Yoshie, T.
2015-12-01
JLDG is a data-grid for the lattice QCD (LQCD) community in Japan. Several large research groups in Japan have been working on lattice QCD simulations using supercomputers distributed over distant sites. The JLDG provides such collaborations with an efficient method of data management and sharing. File servers installed on 9 sites are connected to the NII SINET VPN and are bound into a single file system with the GFarm. The file system looks the same from any sites, so that users can do analyses on a supercomputer on a site, using data generated and stored in the JLDG at a different site. We present a brief description of hardware and software of the JLDG, including a recently developed subsystem for cooperating with the HPCI shared storage, and report performance and statistics of the JLDG. As of April 2015, 15 research groups (61 users) store their daily research data of 4.7PB including replica and 68 million files in total. Number of publications for works which used the JLDG is 98. The large number of publications and recent rapid increase of disk usage convince us that the JLDG has grown up into a useful infrastructure for LQCD community in Japan.
Camp, Cameron J.; Lee, Michelle M.
2012-01-01
Montessori-based activities for persons with dementia have been used to successfully provide opportunities for programming between older adults and preschool children in shared site. intergenerational care programs. Such intergenerational programming allows older adults with dementia to fulfill roles of teacher or mentor to younger children or as collaborative workmates for persons with more advanced dementia while providing children with positive one-on-one interactions with older adults. We review several studies using this approach, describe characteristics of the programs, participants and results obtained and provide recommendations for those interested in extending this line of work. PMID:22423215
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Tingting; Chang, Chin -Yuan; Lohman, Jeremy R.
Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us tomore » propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.« less
NASA Astrophysics Data System (ADS)
Lanciotti, E.; Merino, G.; Bria, A.; Blomer, J.
2011-12-01
In a distributed computing model as WLCG the software of experiment specific application software has to be efficiently distributed to any site of the Grid. Application software is currently installed in a shared area of the site visible for all Worker Nodes (WNs) of the site through some protocol (NFS, AFS or other). The software is installed at the site by jobs which run on a privileged node of the computing farm where the shared area is mounted in write mode. This model presents several drawbacks which cause a non-negligible rate of job failure. An alternative model for software distribution based on the CERN Virtual Machine File System (CernVM-FS) has been tried at PIC, the Spanish Tierl site of WLCG. The test bed used and the results are presented in this paper.
Afriat-Jurnou, Livnat; Jackson, Colin J; Tawfik, Dan S
2012-08-07
Only decades after the introduction of organophosphate pesticides, bacterial phosphotriesterases (PTEs) have evolved to catalyze their degradation with remarkable efficiency. Their closest known relatives, lactonases, with promiscuous phosphotriasterase activity, dubbed PTE-like lactonases (PLLs), share only 30% sequence identity and also differ in the configuration of their active-site loops. PTE was therefore presumed to have evolved from a yet unknown PLL whose primary activity was the hydrolysis of quorum sensing homoserine lactones (HSLs) (Afriat et al. (2006) Biochemistry 45, 13677-13686). However, how PTEs diverged from this presumed PLL remains a mystery. In this study we investigated loop remodeling as a means of reconstructing a homoserine lactonase ancestor that relates to PTE by few mutational steps. Although, in nature, loop remodeling is a common mechanism of divergence of enzymatic functions, reproducing this process in the laboratory is a challenge. Structural and phylogenetic analyses enabled us to remodel one of PTE's active-site loops into a PLL-like configuration. A deletion in loop 7, combined with an adjacent, highly epistatic, point mutation led to the emergence of an HSLase activity that is undetectable in PTE (k(cat)/K(M) values of up to 2 × 10(4)). The appearance of the HSLase activity was accompanied by only a minor decrease in PTE's paraoxonase activity. This specificity change demonstrates the potential role of bifunctional intermediates in the divergence of new enzymatic functions and highlights the critical contribution of loop remodeling to the rapid divergence of new enzyme functions.
Puig-Barberà, Joan; Burtseva, Elena; Yu, Hongjie; Cowling, Benjamin J; Badur, Selim; Kyncl, Jan; Sominina, Anna
2016-08-22
The Global Influenza Hospital Surveillance Network (GIHSN) has established a prospective, active surveillance, hospital-based epidemiological study to collect epidemiological and virological data for the Northern and Southern Hemispheres over several consecutive seasons. It focuses exclusively on severe cases of influenza requiring hospitalization. A standard protocol is shared between sites allowing comparison and pooling of results. During the 2014-2015 influenza season, the GIHSN included seven coordinating sites from six countries (St. Petersburg and Moscow, Russian Federation; Prague, Czech Republic; Istanbul, Turkey; Beijing, China; Valencia, Spain; and Rio de Janeiro, Brazil). Here, we present the detailed epidemiological and influenza vaccine effectiveness findings for the Northern Hemisphere 2014-2015 influenza season.
Report on July 2015 Additional Protocol Coordinators Best Practices Workshop
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gitau, Ernest T.N.; Burbank, Roberta L.; Finch, Valerie A.
After 10 years of implementation experience, the Office of Nonproliferation and Arms Control (NPAC) within the Department of Energy/National Nuclear Security Administration (DOE/NNSA) conducted the Additional Protocol (AP) Coordinators Best Practices Workshop at Oak Ridge National Laboratory from July 29-30, 2015. The goal of this workshop was to identify implementation best practices, lessons learned, and compliance challenges from the various Additional Protocol Coordinators (APCs) at each laboratory in the DOE/NNSA complex and associated sites. The workshop provided the opportunity for participants to share their insights and establish networks that APCs can utilize to continue to discuss challenges (new and old),more » identify best practices, and enhance communication and coordination for reporting multi-lab research projects during review activities. Workshop participants included DOE/NNSA HQ, laboratory and site APCs, seasoned experts, members of the original implementation outreach team, and Field Element and site security representatives.« less
Knutson, Stacy T.; Westwood, Brian M.; Leuthaeuser, Janelle B.; Turner, Brandon E.; Nguyendac, Don; Shea, Gabrielle; Kumar, Kiran; Hayden, Julia D.; Harper, Angela F.; Brown, Shoshana D.; Morris, John H.; Ferrin, Thomas E.; Babbitt, Patricia C.
2017-01-01
Abstract Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification—amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two‐Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure‐Function Linkage Database, SFLD) self‐identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self‐identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well‐curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP‐identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F‐measure and performance analysis on the enolase search results and comparison to GEMMA and SCI‐PHY demonstrate that TuLIP avoids the over‐division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results. PMID:28054422
Knutson, Stacy T; Westwood, Brian M; Leuthaeuser, Janelle B; Turner, Brandon E; Nguyendac, Don; Shea, Gabrielle; Kumar, Kiran; Hayden, Julia D; Harper, Angela F; Brown, Shoshana D; Morris, John H; Ferrin, Thomas E; Babbitt, Patricia C; Fetrow, Jacquelyn S
2017-04-01
Protein function identification remains a significant problem. Solving this problem at the molecular functional level would allow mechanistic determinant identification-amino acids that distinguish details between functional families within a superfamily. Active site profiling was developed to identify mechanistic determinants. DASP and DASP2 were developed as tools to search sequence databases using active site profiling. Here, TuLIP (Two-Level Iterative clustering Process) is introduced as an iterative, divisive clustering process that utilizes active site profiling to separate structurally characterized superfamily members into functionally relevant clusters. Underlying TuLIP is the observation that functionally relevant families (curated by Structure-Function Linkage Database, SFLD) self-identify in DASP2 searches; clusters containing multiple functional families do not. Each TuLIP iteration produces candidate clusters, each evaluated to determine if it self-identifies using DASP2. If so, it is deemed a functionally relevant group. Divisive clustering continues until each structure is either a functionally relevant group member or a singlet. TuLIP is validated on enolase and glutathione transferase structures, superfamilies well-curated by SFLD. Correlation is strong; small numbers of structures prevent statistically significant analysis. TuLIP-identified enolase clusters are used in DASP2 GenBank searches to identify sequences sharing functional site features. Analysis shows a true positive rate of 96%, false negative rate of 4%, and maximum false positive rate of 4%. F-measure and performance analysis on the enolase search results and comparison to GEMMA and SCI-PHY demonstrate that TuLIP avoids the over-division problem of these methods. Mechanistic determinants for enolase families are evaluated and shown to correlate well with literature results. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.
Li, Yongchao; Wang, Yang; Jiang, Haobo; Deng, Junpeng
2009-01-01
Arthropod phenoloxidase (PO) generates quinones and other toxic compounds to sequester and kill pathogens during innate immune responses. It is also involved in wound healing and other physiological processes. Insect PO is activated from its inactive precursor, prophenoloxidase (PPO), by specific proteolysis via a serine protease cascade. Here, we report the crystal structure of PPO from a lepidopteran insect at a resolution of 1.97 Å, which is the initial structure for a PPO from the type 3 copper protein family. Manduca sexta PPO is a heterodimer consisting of 2 homologous polypeptide chains, PPO1 and PPO2. The active site of each subunit contains a canonical type 3 di-nuclear copper center, with each copper ion coordinated with 3 structurally conserved histidines. The acidic residue Glu-395 located at the active site of PPO2 may serve as a general base for deprotonation of monophenolic substrates, which is key to the ortho-hydroxylase activity of PO. The structure provides unique insights into the mechanism by which type 3 copper proteins differ in their enzymatic activities, albeit sharing a common active center. A drastic change in electrostatic surface induced on cleavage at Arg-51 allows us to propose a model for localized PPO activation in insects. PMID:19805072
Structure of nerve growth factor complexed with the shared neurotrophin receptor p75.
He, Xiao-Lin; Garcia, K Christopher
2004-05-07
Neurotrophins are secreted growth factors critical for the development and maintenance of the vertebrate nervous system. Neurotrophins activate two types of cell surface receptors, the Trk receptor tyrosine kinases and the shared p75 neurotrophin receptor. We have determined the 2.4 A crystal structure of the prototypic neurotrophin, nerve growth factor (NGF), complexed with the extracellular domain of p75. Surprisingly, the complex is composed of an NGF homodimer asymmetrically bound to a single p75. p75 binds along the homodimeric interface of NGF, which disables NGF's symmetry-related second p75 binding site through an allosteric conformational change. Thus, neurotrophin signaling through p75 may occur by disassembly of p75 dimers and assembly of asymmetric 2:1 neurotrophin/p75 complexes, which could potentially engage a Trk receptor to form a trimolecular signaling complex.
NASA Astrophysics Data System (ADS)
Chinn, Pauline W. U.
2006-09-01
This three year study of P-12 professional development is grounded in sociocultural theories that hold that building knowledge and relationships among individuals from different cultural backgrounds entails joint activity toward common goals and cultural dialogues mediated by cultural translators. Sixty P-12 pre and in-service teachers in a year long interdisciplinary science curriculum course shared the goal of developing culturally relevant, standards-based science curricula for Native Hawai'ian students. Teachers and Native Hawai'ian instructors lived and worked together during a five day culture-science immersion in rural school and community sites and met several times at school, university, and community sites to build knowledge and share programs. Teachers were deeply moved by immersion experiences, learned to connect cultural understandings, e.g., a Hawai'ian sense of place and curriculum development, and highly valued collaborating with peers on curriculum development and implementation. The study finds that long term professional development providing situated learning through cultural immersion, cultural translators, and interdisciplinary instruction supports the establishment of communities of practice in which participants develop the cross-cultural knowledge and literacy needed for the development of locally relevant, place and standards-based curricula and pedagogy.
U.S. Initiatives to Promote Global Internet Freedom: Issues, Policy, and Technology
2010-03-17
video sharing sites, and other tools of today’s communications technology has proven to be an unprecedented and often disruptive force in some closed...using newer tools, such as blogs, social networks, video sharing sites, and other aspects of today’s communications technology to express their...Iranians sent VOA over 300 videos a day, along with thousands of still pictures, e-mails, and telephone calls to the agency.2 A variety of control
Information Sharing and Knowledge Sharing as Communicative Activities
ERIC Educational Resources Information Center
Savolainen, Reijo
2017-01-01
Introduction: This paper elaborates the picture of information sharing and knowledge sharing as forms of communicative activity. Method: A conceptual analysis was made to find out how researchers have approached information sharing and knowledge sharing from the perspectives of transmission and ritual. The findings are based on the analysis of one…
NASA/MSFC/NSSTC Science Communication Roundtable
NASA Technical Reports Server (NTRS)
Adams, Mitzi L.; Gallagher, D. L.; Koczor, R. J.; Whitaker, Ann F. (Technical Monitor)
2001-01-01
For the last several years the Science Directorate at Marshall Space Flight Center has carried out a diverse program of Internet-based science communication. The Directorate's Science Roundtable includes active researchers, NASA public relations, educators, and administrators. The Science@NASA award-winning family of Web sites features science, mathematics, and space news. The program includes extended stories about NASA science, a curriculum resource for teachers tied to national education standards, on-line activities for students, and webcasts of real-time events. Science stories cover a variety of space-related subjects and are expressed in simple terms everyone can understand. The sites address such questions as: what is space weather, what's in the heart of a hurricane, can humans live on Mars, and what is it like to live aboard the International Space Station? Along with a new look, the new format now offers articles organized by subject matter, such as astronomy, living in space, earth science or biology. The focus of sharing real-time science related events has been to involve and excite students and the public about science. Events have involved meteor showers, solar eclipses, natural very low frequency radio emissions, and amateur balloon flights. In some cases broadcasts accommodate active feedback and questions from Internet participants. Information will be provided about each member of the Science@NASA web sites.
Social Networking Sites as Virtual Communities of Practice: A Mixed Method Study
ERIC Educational Resources Information Center
Davis, Lorretta J.
2010-01-01
Membership in social networking sites is increasing rapidly. Social networking sites serve many purposes including networking, communication, recruitment, and sharing knowledge. Social networking sites, public or private, may be hosted on applications such as Facebook and LinkedIn. As individuals begin to follow and participate in social…
The cost structure of routine infant immunization services: a systematic analysis of six countries
Geng, Fangli; Suharlim, Christian; Brenzel, Logan; Resch, Stephen C; Menzies, Nicolas A
2017-01-01
Abstract Little information exists on the cost structure of routine infant immunization services in low- and middle-income settings. Using a unique dataset of routine infant immunization costs from six countries, we estimated how costs were distributed across budget categories and programmatic activities, and investigated how the cost structure of immunization sites varied by country and site characteristics. The EPIC study collected data on routine infant immunization costs from 319 sites in Benin, Ghana, Honduras, Moldova, Uganda, Zambia, using a standardized approach. For each country, we estimated the economic costs of infant immunization by administrative level, budget category, and programmatic activity from a programme perspective. We used regression models to describe how costs within each category were related to site operating characteristics and efficiency level. Site-level costs (incl. vaccines) represented 77–93% of national routine infant immunization costs. Labour and vaccine costs comprised 14–69% and 13–69% of site-level cost, respectively. The majority of site-level resources were devoted to service provision (facility-based or outreach), comprising 48–78% of site-level costs across the six countries. Based on the regression analyses, sites with the highest service volume had a greater proportion of costs devoted to vaccines, with vaccine costs per dose relatively unaffected by service volume but non-vaccine costs substantially lower with higher service volume. Across all countries, more efficient sites (compared with sites with similar characteristics) had a lower cost share devoted to labour. The cost structure of immunization services varied substantially between countries and across sites within each country, and was related to site characteristics. The substantial variation observed in this sample suggests differences in operating model for otherwise similar sites, and further understanding of these differences could reveal approaches to improve efficiency and performance of immunization sites. PMID:28575193
The cost structure of routine infant immunization services: a systematic analysis of six countries.
Geng, Fangli; Suharlim, Christian; Brenzel, Logan; Resch, Stephen C; Menzies, Nicolas A
2017-10-01
Little information exists on the cost structure of routine infant immunization services in low- and middle-income settings. Using a unique dataset of routine infant immunization costs from six countries, we estimated how costs were distributed across budget categories and programmatic activities, and investigated how the cost structure of immunization sites varied by country and site characteristics. The EPIC study collected data on routine infant immunization costs from 319 sites in Benin, Ghana, Honduras, Moldova, Uganda, Zambia, using a standardized approach. For each country, we estimated the economic costs of infant immunization by administrative level, budget category, and programmatic activity from a programme perspective. We used regression models to describe how costs within each category were related to site operating characteristics and efficiency level. Site-level costs (incl. vaccines) represented 77-93% of national routine infant immunization costs. Labour and vaccine costs comprised 14-69% and 13-69% of site-level cost, respectively. The majority of site-level resources were devoted to service provision (facility-based or outreach), comprising 48-78% of site-level costs across the six countries. Based on the regression analyses, sites with the highest service volume had a greater proportion of costs devoted to vaccines, with vaccine costs per dose relatively unaffected by service volume but non-vaccine costs substantially lower with higher service volume. Across all countries, more efficient sites (compared with sites with similar characteristics) had a lower cost share devoted to labour. The cost structure of immunization services varied substantially between countries and across sites within each country, and was related to site characteristics. The substantial variation observed in this sample suggests differences in operating model for otherwise similar sites, and further understanding of these differences could reveal approaches to improve efficiency and performance of immunization sites. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.
The Creation of a Pediatric Hospital Medicine Dashboard: Performance Assessment for Improvement.
Fox, Lindsay Anne; Walsh, Kathleen E; Schainker, Elisabeth G
2016-07-01
Leaders of pediatric hospital medicine (PHM) recommended a clinical dashboard to monitor clinical practice and make improvements. To date, however, no programs report implementing a dashboard including the proposed broad range of metrics across multiple sites. We sought to (1) develop and populate a clinical dashboard to demonstrate productivity, quality, group sustainability, and value added for an academic division of PHM across 4 inpatient sites; (2) share dashboard data with division members and administrations to improve performance and guide program development; and (3) revise the dashboard to optimize its utility. Division members proposed a dashboard based on PHM recommendations. We assessed feasibility of data collection and defined and modified metrics to enable collection of comparable data across sites. We gathered data and shared the results with division members and administrations. We collected quarterly and annual data from October 2011 to September 2013. We found comparable metrics across all sites for descriptive, productivity, group sustainability, and value-added domains; only 72% of all quality metrics were tracked in a comparable fashion. After sharing the data, we saw increased timeliness of nursery discharges and an increase in hospital committee participation and grant funding. PHM dashboards have the potential to guide program development, mobilize faculty to improve care, and demonstrate program value to stakeholders. Dashboard implementation at other institutions and data sharing across sites may help to better define and strengthen the field of PHM by creating benchmarks and help improve the quality of pediatric hospital care. Copyright © 2016 by the American Academy of Pediatrics.
Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*
Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.
2014-01-01
Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313
Intoxigenic digital spaces? Youth, social networking sites and alcohol marketing.
Griffiths, Richard; Casswell, Sally
2010-09-01
To examine how young people in New Zealand engage with alcohol and reproduce alcohol marketing messages and alcohol-related branding in 'Bebo', a popular social networking site (SNS) on the Internet. Data are drawn from information posted on approximately 150 Bebo Web pages and analysed by way of textual analysis and cyberspace ethnography. Social networking sites, such as Bebo, provide young people with a digital space in which to share a range of alcohol marketing messages via peer-to-peer transmission. Bebo also enables youth to communicate to one another how they consume alcohol and their views of alcohol marketing messages. The information being shared by young people who use Bebo is openly provided in the form of personal information, forum comments, digital photographs and answering quizzes about their engagement with alcohol. Through this sharing of information in the digital Internet environment, young people are creating 'intoxigenic social identities' as well as 'intoxigenic digital spaces' that further contribute towards the normalisation of youth consumption of alcohol. A better understanding of how youth are using the Internet to share their experiences with alcohol and engagement with alcohol-related messages is crucial to public health research as alcohol marketing practices rapidly evolve.
Francis-Coad, Jacqueline; Etherton-Beer, Christopher; Bulsara, Caroline; Nobre, Debbie; Hill, Anne-Marie
2017-03-01
Objective This study evaluates whether a community of practice (CoP) could conduct a falls prevention clinical audit and identify gaps in falls prevention practice requiring action. Methods Cross-sectional falls prevention clinical audits were conducted in 13 residential aged care (RAC) sites of a not-for-profit organisation providing care to a total of 779 residents. The audits were led by an operationalised CoP assisted by site clinical staff. A CoP is a group of people with a shared interest who get together to innovate for change. The CoP was made up of self-nominated staff representing all RAC sites and comprised of staff from various disciplines with a shared interest in falls prevention. Results All 13 (100%) sites completed the audit. CoP conduct of the audit met identified criteria for an effective clinical audit. The priorities for improvement were identified as increasing the proportion of residents receiving vitamin D supplementation (mean 41.5%, s.d. 23.7) and development of mandatory falls prevention education for staff and a falls prevention policy, as neither was in place at any site. CoP actions undertaken included a letter to visiting GPs requesting support for vitamin D prescription, surveys of care staff and residents to inform falls education development, defining falls and writing a falls prevention policy. Conclusion A CoP was able to effectively conduct an evidence-based falls prevention activity audit and identify gaps in practice. CoP members were well positioned, as site staff, to overcome barriers and facilitate action in falls prevention practice. What is known about the topic? Audit and feedback is an effective way of measuring clinical quality and safety. CoPs have been established in healthcare using workplace staff to address clinical problems but little is known about their ability to audit and influence practice change. What does this paper add? This study contributes to the body of knowledge on CoPs in healthcare by evaluating the performance of one in the domain of falls prevention audit action. What are the implications for practitioners? A CoP is an effective model to engage staff in the clinical audit process. Clinical audits can raise staff awareness of gaps in practice and motivate staff to plan and action change as recommended in best practice guidelines.
Rosas, Scott R; Cope, Marie T; Villa, Christie; Motevalli, Mahnaz; Utech, Jill; Schouten, Jeffrey T
2014-04-01
Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi-network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross-network coordinating centre, and creating common budget and payment mechanisms. The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings. © 2013 John Wiley & Sons Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Artavanis-Tsakonas, Katerina; Weihofen, Wilhelm A.; Antos, John M.
Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed themore » identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected.« less
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-31
... Trading of Shares of the Pring Turner Business Cycle ETF Under NYSE Arca Equities Rule 8.600 October 25... Turner Business Cycle ETF. The text of the proposed rule change is available on the Exchange's Web site... and trade shares (``Shares'') of the Pring Turner Business Cycle ETF (``Fund'') under NYSE Arca...
Kant, Vishnu; Vijayakumar, Saravanan; Sahoo, Ganesh Chandra; Chaudhery, Shailendra S; Das, Pradeep
2018-02-07
OASS is a specific enzyme that helps Leishmania parasite to survive the oxidative stress condition in human macrophages. SAT C-terminal peptides in several organisms, including Leishmania, were reported to inhibit or reduce the activity of OASS. Small peptide and small molecules mimicking the SAT C-terminal residues are designed and tested for the inhibition of OASS in different organisms. Hence, in this study, all the possible tetra-peptide combinations were designed and screened based on the docking ability with Leishmania donovani OASS (Ld-OASS). The top ranked peptides were further validated for the stability using 50 ns molecular dynamic simulation. In order to identify the better binding capability of the peptides, the top peptides complexed with Ld-OASS were also subjected to molecular dynamic simulation. The docking and simulation results favored the peptide EWSI to possess greater advantage than previously reported peptide (DWSI) in binding with Ld-OASS active site. Also, screening of non-peptide inhibitor of Asinex Biodesign library based on the shape similarity of EWSI and DWSI was performed. The top similar molecules of each peptides were docked on to Ld-OASS active site and subsequently simulated for 20 ns. The results suggested that the ligand that shares high shape similarity with EWSI possess better binding capability than the ligand that shares high shape similarity with DWSI. This study revealed that the tetra-peptide EWSI had marginal advantage over DWSI in binding with Ld-OASS, thereby providing basis for defining a pharmacophoric scaffold for the design of peptidomimetic inhibitors as well as non-peptide inhibitors of Ld-OASS.
Expert knowledge in palliative care on the World Wide Web: palliativedrugs.org.
Gavrin, Jonathan
2009-01-01
In my last Internet-related article, I speculated that social networking would be the coming wave in the effort to share knowledge among experts in various disciplines. At the time I did not know that a palliative care site on the World Wide Web (WWW), palliativedrugs.com, already provided the infrastructure for sharing expert knowledge in the field. The Web site is an excellent traditional formulary but it is primarily devoted to "unlicensed" ("off-label") use of medications in palliative care, something we in the specialty often do with little to support our interventions except shared knowledge and experience. There is nothing fancy about this Web site. In a good way, its format is a throwback to Web sites of the 1990s. In only the loosest sense can one describe it as "multimedia." Yet, it provides the perfect forum for expert knowledge and is a "must see" resource. Its existing content is voluminous and reliable, filtered and reviewed by renowned clinicians and educators in the field. Although its origin and structure were not specifically designed for social or professional networking, the Web site's format makes it a natural way for practitioners around the world to contribute to an ever-growing body of expertise in palliative care.
Muzaffar, Razi; Frye, Sarah A; McMunn, Anna; Ryan, Kelley; Lattanze, Ron; Osman, Medhat M
2017-12-01
A novel quality control and quality assurance device provides time-activity curves that can identify and characterize PET/CT radiotracer infiltration at the injection site during the uptake phase. The purpose of this study was to compare rates of infiltration detected by the device with rates detected by physicians. We also assessed the value of using the device to improve injection results in our center. Methods: 109 subjects consented to the study. All had passive device sensors applied to their skin near the injection site and mirrored on the contralateral arm during the entire uptake period. Nuclear medicine physicians reviewed standard images for the presence of dose infiltration. Sensor-generated time-activity curves were independently examined and then compared with the physician reports. Injection data captured by the software were analyzed, and the results were provided to the technologists. Improvement measures were implemented, and rates were remeasured. Results: Physician review of the initial 40 head-to-toe field-of-view images identified 15 cases (38%) of dose infiltration (9 minor, 5 moderate, and 1 significant). Sensor time-activity curves on these 40 cases independently identified 22 cases (55%) of dose infiltration (16 minor, 5 moderate, and 1 significant). After the time-activity curve results and the contributing factor analysis were shared with technologists, injection techniques were modified and an additional 69 cases were studied. Of these, physician review identified 17 cases (25%) of infiltration (13 minor, 3 moderate, and 1 significant), a 34% decline. Sensor time-activity curves identified 4 cases (6%) of infiltration (2 minor and 2 moderate), an 89% decline. Conclusion: The device provides valuable quality control information for each subject. Time-activity curves can further characterize visible infiltration. Even when the injection site was out of the field of view, the time-activity curves could still detect and characterize infiltration. Our initial experience showed that the quality assurance information obtained from the device helped reduce the rate and severity of infiltration. The device revealed site-specific contributing factors that helped nuclear medicine physicians and technologists customize their quality improvement efforts to these site-specific issues. Reducing infiltration can improve image quality and SUV quantification, as well as the ability to minimize variability in a site's PET/CT results. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.
Differential Sox10 Genomic Occupancy in Myelinating Glia
Lopez-Anido, Camila; Sun, Guannan; Koenning, Matthias; Srinivasan, Rajini; Hung, Holly A.; Emery, Ben; Keles, Sunduz; Svaren, John
2015-01-01
Myelin is formed by specialized myelinating glia: oligodendrocytes and Schwann cells in the central and peripheral nervous systems, respectively. While there are distinct developmental aspects and regulatory pathways in these two cell types, myelination in both systems requires the transcriptional activator Sox10. Sox10 interacts with cell type-specific transcription factors at some loci to induce myelin gene expression, but it is largely unknown how Sox10 transcriptional networks globally compare between oligodendrocytes and Schwann cells. We used in vivo ChIP-Seq analysis of spinal cord and peripheral nerve (sciatic nerve) to identify unique and shared Sox10 binding sites and assess their correlation with active enhancers and transcriptional profiles in oligodendrocytes and Schwann cells. Sox10 binding sites overlap with active enhancers and critical cell type-specific regulators of myelination, such as Olig2 and Myrf in oligodendrocytes, and Egr2/Krox20 in Schwann cells. Sox10 sites also associate with genes critical for myelination in both oligodendrocytes and Schwann cells, and are found within super-enhancers previously defined in brain. In Schwann cells, Sox10 sites contain binding motifs of putative partners in the Sp/Klf, Tead, and nuclear receptor protein families. Specifically, siRNA analysis of nuclear receptors Nr2f1 and Nr2f2 revealed downregulation of myelin genes Mbp and Ndrg1 in primary Schwann cells. Our analysis highlights different mechanisms that establish cell type-specific genomic occupancy of Sox10, which reflects the unique characteristics of oligodendrocyte and Schwann cell differentiation. PMID:25974668
Sautner, Viktor; Friedrich, Mascha Miriam; Lehwess-Litzmann, Anja; Tittmann, Kai
2015-07-28
Transaldolase (TAL) and fructose-6-phosphate aldolase (FSA) both belong to the class I aldolase family and share a high degree of structural similarity and sequence identity. The molecular basis of the different reaction specificities (transferase vs aldolase) has remained enigmatic. A notable difference between the active sites is the presence of either a TAL-specific Glu (Gln in FSA) or a FSA-specific Tyr (Phe in TAL). Both residues seem to have analoguous multifunctional catalytic roles but are positioned at different faces of the substrate locale. We have engineered a TAL double variant (Glu to Gln and Phe to Tyr) with an active site resembling that of FSA. This variant indeed exhibits aldolase activity as its main activity with a catalytic efficiency even larger than that of authentic FSA, while TAL activity is greatly impaired. Structural analysis of this variant in complex with the dihydroxyacetone Schiff base formed upon substrate cleavage identifies the introduced Tyr (genuine in FSA) to catalyze protonation of the central carbanion-enamine intermediate as a key determinant of the aldolase reaction. Our studies pinpoint that the Glu in TAL and the Tyr in FSA, although located at different positions at the active site, similarly act as bona fide acid-base catalysts in numerous catalytic steps, including substrate binding, dehydration of the carbinolamine, and substrate cleavage. We propose that the different spatial positions of the multifunctional Glu in TAL and of the corresponding multifunctional Tyr in FSA relative to the substrate locale are critically controlling reaction specificity through either unfavorable (TAL) or favorable (FSA) geometry of proton transfer onto the common carbanion-enamine intermediate. The presence of both potential acid-base residues, Glu and Tyr, in the active site of TAL has deleterious effects on substrate binding and cleavage, most likely resulting from a differently organized H-bonding network. Large-scale motions of the protein associated with opening and closing of the active site that seem to bear relevance for catalysis are observed as covalent intermediates are exclusively observed in the "closed" conformation of the active site. Pre-steady-state kinetics are used to monitor catalytic processes and structural transitions and to refine the kinetic framework of TAL catalysis.
Overproduction in Escherichia coli and Characterization of a Soybean Ferric Leghemoglobin Reductase.
Ji, L.; Becana, M.; Sarath, G.; Shearman, L.; Klucas, R. V.
1994-01-01
We previously cloned and sequenced a cDNA encoding soybean ferric leghemoglobin reductase (FLbR), an enzyme postulated to play an important role in maintaining leghemoglobin in a functional ferrous state in nitrogen-fixing root nodules. This cDNA was sub-cloned into an expression plasmid, pTrcHis C, and overexpressed in Escherichia coli. The recombinant FLbR protein, which was purified by two steps of column chromatography, was catalytically active and fully functional. The recombinant FLbR cross-reacted with antisera raised against native FLbR purified from soybean root nodules. The recombinant FLbR, the native FLbR purified from soybean (Glycine max L.) root nodules, and dihydrolipoamide dehydrogenases from pig heart and yeast had similar but not identical ultraviolet-visible absorption and fluorescence spectra, cofactor binding, and kinetic properties. FLbR shared common structural features in the active site and prosthetic group binding sites with other pyridine nucleotide-disulfide oxidoreductases such as dihydrolipoamide dehydrogenases, but displayed different microenvironments for the prosthetic groups. PMID:12232320
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, about 150 followers of the agency’s Twitter account listen to presentations about NASA’s Juno mission to Jupiter during Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of Juno prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, about 150 followers of the agency’s Twitter account listen to presentations about NASA’s Juno mission to Jupiter during Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of Juno prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, NASA Chief Scientist Waleed Abdalati speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Gianni M. Woods
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Jim Adams, NASA deputy director of Planetary Science, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, television personality Bill Nye, the science guy, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Fletcher Hildreth
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Scott Bolton, Juno primary investigator from the Southwest Research Institute in San Antonio, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, NASA Administrator Charles Bolden speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Gianni M. Woods
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Chris Brosious, Juno chief systems engineer for Lockheed Martin, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Toby Owen, Juno co-investigator from the University of Hawaii, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, about 150 followers of the agency’s Twitter account listen to presentations about NASA’s Juno mission to Jupiter during Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of Juno prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Fletcher Hildreth
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Jan Chodas, Juno project manager from the Jet Propulsion Laboratory in Pasadena, Calif., speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, television personality Bill Nye, the science guy, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Fletcher Hildreth
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, NASA Tweetup coordinator Stephanie Schierholz welcomes about 150 tweeters to Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Steve Levin, Juno project scientist from the Jet Propulsion Laboratory in Pasadena, Calif., speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, NASA Administrator Charles Bolden speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Gianni M. Woods
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Steve Levin, Juno project scientist from the Jet Propulsion Laboratory in Pasadena, Calif., speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, about 150 followers of the agency’s Twitter account listen to presentations about NASA’s Juno mission to Jupiter during Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of Juno prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Fletcher Hildreth
NASA Astrophysics Data System (ADS)
Bhattacharyya, Dhiman; Depci, Tolga; Prisbrey, Keith; Miller, Jan D.
Despite tremendous developments in industrial use of activated carbon (AC) for gold adsorption, specific aurodicyanide [Au(CN)2-] adsorption sites on the carbon have intrigued researchers. The graphitic structure of AC has been well established. Previously radiochemical and now, XPS and Raman characterizations have demonstrated higher site-specific gold adsorption on graphitic edges. Morphological characterizations have revealed the presence of slit-pores (5-10 Å). Molecular-dynamics-simulation (MDS) performed on graphitic slit-pores illustrated gold-cyanide ion-pair preferentially adsorbs on edges. Ab-initio simulations predicted lower barrier for electron sharing in pores with aurodic yanide, indicating tighter bonding than graphitic surface and was well supported by Gibbs energy calculations too. Interaction energy as function of the separation distance indicated tighter bonding of gold cyanide to the graphite edges than water molecules. Selective adsorption of aurodicyanide ion-pair seems to be related to low polarity of gold complex and its accommodation at graphitic edges.
Jarrott, Shannon E; Smith, Cynthia L
2011-02-01
We assessed whether a shared site intergenerational care program informed by contact theory contributed to more desirable social behaviors of elders and children during intergenerational programming than a center with a more traditional programming approach that lacks some or all of the contact theory tenets. We observed 59 elder and child participants from the two sites during intergenerational activities. Using the Intergenerational Observation Scale, we coded participants' predominant behavior in 15-s intervals through each activity's duration. We then calculated for each individual the percentage of time frames each behavior code was predominant. Participants at the theory-based program demonstrated higher rates of intergenerational interaction, higher rates of solitary behavior, and lower rates of watching than at the traditional program. Contact theory tenets were optimized when coupled with evidence-based practices. Intergenerational programs with stakeholder support that promotes equal group status, cooperation toward a common goal, and mechanisms of friendship among participants can achieve important objectives for elder and child participants in care settings.
Olson, J C
1993-01-01
Diphtheria toxin (DT) and Pseudomonas aeruginosa exotoxin A have the same molecular mechanism of toxicity; both toxins ADP-ribosylate a modified histidine residue in elongation factor 2. To help identify amino acids involved in this reaction, sequences in DT that share homology with P. aeruginosa exotoxin A were synthesized and examined for a role in the ADP-ribosyltransferase reaction. By using this approach, residues 32 to 54 of DT were found to define an epitope associated with antibody-mediated inhibition of DT enzyme activity. This lends further support to the notion that residues in this region of DT are involved in the enzymatic reaction. PMID:8423159
U.S. Spacesuit Knowledge Capture Status and Initiatives in Fiscal Year 2014
NASA Technical Reports Server (NTRS)
Chullen, Cinda; Oliva, Vladenka R.
2015-01-01
Since its 2008 inception, the NASA U.S. Spacesuit Knowledge Capture (KC) program has shared historical spacesuit information with engineers and other technical team members to expand their understanding of the spacesuit's evolution, known capability and limitations, and future desires and needs for its use. As part of the U.S. Spacesuit KC program, subject-matter experts have delivered presentations, held workshops, and participated in interviews to share valuable spacesuit lessons learned to ensure this vital information will survive for existing and future generations to use. These events have included spacesuit knowledge from the inception of NASA's first spacesuit to current spacesuit design. To ensure that this information is shared with the entire NASA community and other interested or invested entities, these KC events were digitally recorded and transcribed to be uploaded onto several applicable NASA Web sites. This paper discusses the various Web sites that the KC events are uploaded to and possible future sites that will channel this information.
U.S. Spacesuit Knowledge Capture Accomplishments in Fiscal Year 2014
NASA Technical Reports Server (NTRS)
Chullen, Cinda; Oliva, Vladenka R.
2015-01-01
Since its 2008 inception, the NASA U.S. Spacesuit Knowledge Capture (KC) program has shared historical spacesuit information with engineers and other technical team members to expand their understanding of the spacesuit's evolution, known capability and limitations, and future desires and needs for its use. As part of the U.S. Spacesuit KC program, subject-matter experts have delivered presentations, held workshops, and participated in interviews to share valuable spacesuit lessons learned to ensure this vital information will survive for existing and future generations to use. These events have included spacesuit knowledge from the inception of NASA's first spacesuit to current spacesuit design. To ensure that this information is shared with the entire NASA community and other interested or invested entities, these KC events were digitally recorded and transcribed to be uploaded onto several applicable NASA Web sites. This paper discusses the various Web sites that the KC events are uploaded to and possible future sites that will channel this information.
Information sharing and relationships on social networking sites.
Steijn, Wouter M P; Schouten, Alexander P
2013-08-01
This article investigates the relationship between sharing personal information and relationship development in the context of social networking sites (SNSs). Information disclosed on these sites could affect relationships in a different manner compared to more traditional interactions, such as instant messaging or face-to-face interaction. Respondents in the age range of 12 to 83 were surveyed about experiences of relationship development as a consequence of contact through Facebook or Hyves-the most popular Dutch SNSs. Results showed a primarily positive effect of information sharing on SNSs on our relationships. Furthermore, relationship development mainly occurs among acquaintances and friends, and public posts are most strongly related to relationship development. These findings suggest that SNSs might affect relationships in a distinct fashion as acquaintances and friends gain access to public self-disclosures that might normally only be reserved for close friends and family. Overall, this study provides an insight into some of the positive aspects of the public nature of SNSs in contrast with the general negative associations.
Ectocranial suture fusion in primates: pattern and phylogeny.
Cray, James; Cooper, Gregory M; Mooney, Mark P; Siegel, Michael I
2014-03-01
Patterns of ectocranial suture fusion among Primates are subject to species-specific variation. In this study, we used Guttman Scaling to compare modal progression of ectocranial suture fusion among Hominidae (Homo, Pan, Gorilla, and Pongo), Hylobates, and Cercopithecidae (Macaca and Papio) groups. Our hypothesis is that suture fusion patterns should reflect their evolutionary relationship. For the lateral-anterior suture sites there appear to be three major patterns of fusion, one shared by Homo-Pan-Gorilla, anterior to posterior; one shared by Pongo and Hylobates, superior to inferior; and one shared by Cercopithecidae, posterior to anterior. For the vault suture pattern, the Hominidae groups reflect the known phylogeny. The data for Hylobates and Cercopithecidae groups is less clear. The vault suture site termination pattern of Papio is similar to that reported for Gorilla and Pongo. Thus, it may be that some suture sites are under larger genetic influence for patterns of fusion, while others are influenced by environmental/biomechanic influences. Copyright © 2013 Wiley Periodicals, Inc.
Detection of Damaged DNA Bases by DNA Glycosylase Enzymes†
Friedman, Joshua I.; Stivers, James T.
2010-01-01
A fundamental and shared process in all forms of life is the use of DNA glycosylase enzymes to excise rare damaged bases from genomic DNA. Without such enzymes, the highly-ordered primary sequences of genes would rapidly deteriorate. Recent structural and biophysical studies are beginning to reveal a fascinating multistep mechanism for damaged base detection that begins with short-range sliding of the glycosylase along the DNA chain in a distinct conformation we refer to as the search complex (SC). Sliding is frequently punctuated by the formation of a transient “interrogation” complex (IC) where the enzyme extrahelically inspects both normal and damaged bases in an exosite pocket that is distant from the active site. When normal bases are presented in the exosite, the IC rapidly collapses back to the SC, while a damaged base will efficiently partition forward into the active site to form the catalytically competent excision complex (EC). Here we review the unique problems associated with enzymatic detection of rare damaged DNA bases in the genome, and emphasize how each complex must have specific dynamic properties that are tuned to optimize the rate and efficiency of damage site location. PMID:20469926
Busk, Peter Kamp; Lange, Lene
2013-06-01
Functional prediction of carbohydrate-active enzymes is difficult due to low sequence identity. However, similar enzymes often share a few short motifs, e.g., around the active site, even when the overall sequences are very different. To exploit this notion for functional prediction of carbohydrate-active enzymes, we developed a simple algorithm, peptide pattern recognition (PPR), that can divide proteins into groups of sequences that share a set of short conserved sequences. When this method was used on 118 glycoside hydrolase 5 proteins with 9% average pairwise identity and representing four characterized enzymatic functions, 97% of the proteins were sorted into groups correlating with their enzymatic activity. Furthermore, we analyzed 8,138 glycoside hydrolase 13 proteins including 204 experimentally characterized enzymes with 28 different functions. There was a 91% correlation between group and enzyme activity. These results indicate that the function of carbohydrate-active enzymes can be predicted with high precision by finding short, conserved motifs in their sequences. The glycoside hydrolase 61 family is important for fungal biomass conversion, but only a few proteins of this family have been functionally characterized. Interestingly, PPR divided 743 glycoside hydrolase 61 proteins into 16 subfamilies useful for targeted investigation of the function of these proteins and pinpointed three conserved motifs with putative importance for enzyme activity. Furthermore, the conserved sequences were useful for cloning of new, subfamily-specific glycoside hydrolase 61 proteins from 14 fungi. In conclusion, identification of conserved sequence motifs is a new approach to sequence analysis that can predict carbohydrate-active enzyme functions with high precision.
Mechanistic, Mutational, and Structural Evaluation of a Taxus Phenylalanine Aminomutase
DOE Office of Scientific and Technical Information (OSTI.GOV)
Feng, Lei; Wanninayake, Udayanga; Strom, Susan
The structure of a phenylalanine aminomutase (TcPAM) from Taxus canadensis has been determined at 2.4 {angstrom} resolution. The active site of the TcPAM contains the signature 4-methylidene-1H-imidazol-5(4H)-one prosthesis, observed in all catalysts of the class I lyase-like family. This catalyst isomerizes (S)-{alpha}-phenylalanine to the (R)-{beta}-isomer by exchange of the NH{sub 2}/H pair. The stereochemistry of the TcPAM reaction product is opposite of the (S)-{beta}-tyrosine made by the mechanistically related tyrosine aminomutase (SgTAM) from Streptomyces globisporus. Since TcPAM and SgTAM share similar tertiary- and quaternary-structures and have several highly conserved aliphatic residues positioned analogously in their active sites for substrate recognition,more » the divergent product stereochemistries of these catalysts likely cannot be explained by differences in active site architecture. The active site of the TcPAM structure also is in complex with (E)-cinnamate; the latter functions as both a substrate and an intermediate. To account for the distinct (3R)-{beta}-amino acid stereochemistry catalyzed by TcPAM, the cinnamate skeleton must rotate the C{sub 1}-C{sub {alpha}} and C{sub ipso}-C{sub {beta}} bonds 180{sup o} in the active site prior to exchange and rebinding of the NH{sub 2}/H pair to the cinnamate, an event that is not required for the corresponding acrylate intermediate in the SgTAM reaction. Moreover, the aromatic ring of the intermediate makes only one direct hydrophobic interaction with Leu-104. A L104A mutant of TcPAM demonstrated an 1.5-fold increase in k{sub cat} and a decrease in K{sub M} values for sterically demanding 3'-methyl-{alpha}-phenylalanine and styryl-{alpha}-alanine substrates, compared to the kinetic parameters for TcPAM. These parameters did not change significantly for the mutant with 4'-methyl-{alpha}-phenylalanine compared to those for TcPAM.« less
ZINC: A Free Tool to Discover Chemistry for Biology
2012-01-01
ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org. PMID:22587354
Khan, Sharib A.; Ancker, Jessica S.; Li, Jianhua; Kaufman, David; Hutchinson, Carly; Cohall, Alwyn; Kukafka, Rita
2009-01-01
GetHealthyHarlem.org is a community website developed on an open-source platform to facilitate collaborative development of health content through participatory action research (PAR) principles. The website was developed to enable the Harlem community to create a shared health and wellness knowledgebase, to enable discourse about local and culturally relevant health information, and to foster social connections between community members and health promotion organizations. The site is gaining active use with more than 9,500 unique site visits in the six months since going live in November, 2008. In ongoing research studies, we are using the website to explore how the PAR model can be applied to the development of a community health website. PMID:20351872
Health Promotion at the Construction Work Site: The Lunch Truck Pilot Study.
Caban-Martinez, Alberto J; Moore, Kevin J; Clarke, Tainya C; Davila, Evelyn P; Clark, John D; Lee, David J; Fleming, Lora E
2018-04-01
The transient nature of construction work makes it difficult to conduct longitudinal worksite-based health promotion activities. As part of a workplace health assessment pilot study, we worked with a commercial lunch truck company to disseminate four types of health education materials including cancer screening, workplace injury prevention, fruit and vegetable consumption, and smoking cessation to construction workers purchasing food items from the truck during their job breaks. Two weeks following the worksite assessment, we followed up with these workers to ascertain their use of the health promotion materials. Of the 54 workers surveyed, 83% reported reviewing and sharing the cancer screening materials with their families, whereas 44% discussed the cancer screening materials with coworkers. Similar proportions of workers reviewed, shared, and discussed the other health promotion materials with their family. Lunch trucks may be an effective strategy and delivery method for educating construction workers on healthy behaviors and injury prevention practices.
Dual control by Cdk1 phosphorylation of the budding yeast APC/C ubiquitin ligase activator Cdh1.
Höckner, Sebastian; Neumann-Arnold, Lea; Seufert, Wolfgang
2016-07-15
The antagonism between cyclin-dependent kinases (Cdks) and the ubiquitin ligase APC/C-Cdh1 is central to eukaryotic cell cycle control. APC/C-Cdh1 targets cyclin B and other regulatory proteins for degradation, whereas Cdks disable APC/C-Cdh1 through phosphorylation of the Cdh1 activator protein at multiple sites. Budding yeast Cdh1 carries nine Cdk phosphorylation sites in its N-terminal regulatory domain, most or all of which contribute to inhibition. However, the precise role of individual sites has remained unclear. Here, we report that the Cdk phosphorylation sites of yeast Cdh1 are organized into autonomous subgroups and act through separate mechanisms. Cdk sites 1-3 had no direct effect on the APC/C binding of Cdh1 but inactivated a bipartite nuclear localization sequence (NLS) and thereby controlled the partitioning of Cdh1 between cytoplasm and nucleus. In contrast, Cdk sites 4-9 did not influence the cell cycle-regulated localization of Cdh1 but prevented its binding to the APC/C. Cdk sites 4-9 reside near two recently identified APC/C interaction motifs in a pattern conserved with the human Cdh1 orthologue. Thus a Cdk-inhibited NLS goes along with Cdk-inhibited APC/C binding sites in yeast Cdh1 to relay the negative control by Cdk1 phosphorylation of the ubiquitin ligase APC/C-Cdh1. © 2016 Höckner et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
Beyond Lecture and Non-Lecture Classrooms: LA-student interactions in Active Learning Classrooms
NASA Astrophysics Data System (ADS)
Gonzalez, Dayana; Kornreich, Hagit; Rodriguez, Idaykis; Monslave, Camila; Pena-Flores, Norma
Our expanded multi-site study on active learning classrooms supported by Learning Assistants (LAs) aims to understand the connections between three classroom elements: the activity, student learning, and how LAs support the learning process in the classroom. At FIU, LAs are used in a variety of active learning settings, from large auditorium settings to studio classroom with movable tables. Our study uses the COPUS observation protocol as a way to characterize LAs behaviors in these classrooms. With a focus on LA-student interactions, our analysis of how LAs interact with students during a 'learning session' generated new observational codes for specific new categories of LA roles. Preliminary results show that LAs spend more time interacting with students in some classes, regardless of the classroom setting, while in other classrooms, LA-student interactions are mostly brief. We discuss how LA-student interactions contribute to the dynamics and mechanism of the socially shared learning activity.
Emergence of the pre-Bötzinger respiratory rhythm generator in the mouse embryo.
Thoby-Brisson, Muriel; Trinh, Jean-Baptiste; Champagnat, Jean; Fortin, Gilles
2005-04-27
To obtain insights into the emergence of rhythmogenic circuits supporting respiration, we monitored spontaneous activities in isolated brainstem and medullary transverse slice preparations of mouse embryos, combining electrophysiological and calcium imaging techniques. At embryonic day 15 (E15), in a restricted region ventral to the nucleus ambiguus, we observed the onset of a sustained high-frequency (HF) respiratory-like activity in addition to a preexisting low-frequency activity having a distinct initiation site, spatial extension, and susceptibility to gap junction blockers. At the time of its onset, the HF generator starts to express the neurokinin 1 receptor, is connected bilaterally, requires active AMPA/kainate glutamatergic synapses, and is modulated by substance P and the mu-opioid agonist D-Ala2-N-Me-Phe4-Glycol5-enkephalin. We conclude that a rhythm generator sharing the properties of the neonatal pre-Bötzinger complex becomes active during E15 in mice.
Controlling Distributed Planning
NASA Technical Reports Server (NTRS)
Clement, Bradley; Barrett, Anthony
2004-01-01
A system of software implements an extended version of an approach, denoted shared activity coordination (SHAC), to the interleaving of planning and the exchange of plan information among organizations devoted to different missions that normally communicate infrequently except that they need to collaborate on joint activities and/or the use of shared resources. SHAC enables the planning and scheduling systems of the organizations to coordinate by resolving conflicts while optimizing local planning solutions. The present software provides a framework for modeling and executing communication protocols for SHAC. Shared activities are represented in each interacting planning system to establish consensus on joint activities or to inform the other systems of consumption of a common resource or a change in a shared state. The representations of shared activities are extended to include information on (1) the role(s) of each participant, (2) permissions (defined as specifications of which participant controls what aspects of shared activities and scheduling thereof), and (3) constraints on the parameters of shared activities. Also defined in the software are protocols for changing roles, permissions, and constraints during the course of coordination and execution.
Beta-globin locus activation regions: conservation of organization, structure, and function.
Li, Q L; Zhou, B; Powers, P; Enver, T; Stamatoyannopoulos, G
1990-01-01
The human beta-globin locus activation region (LAR) comprises four erythroid-specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid-specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function. Images PMID:2236034
[Social media and medical apps: how they can change health communication, education and care].
Santoro, Eugenio
2013-05-01
Social media and medical apps for smartphones and tablets are changing health communication, education and care. This change involves physicians and other health care professionals which for their education, training and updating have started to follow public pages and profiles opened by medical journals and professional societies on the online social networking sites (such as Facebook, Twitter and Google+), to access scientific content (videos, images, slides) available on user-generated contents sites (such as SlideShare, Pinterest and YouTube) or on health professional online communities such as Sermo, and to use medical and health apps on their smartphones and tablets. As shown by a number of experiences conducted in US by health institutions such as the Centers for Disease Control and Prevention of Atlanta and hospitals such a the Mayo Clinic, these tools are also transforming the way to make health promotion activities and communication, promote healthy habits and lifestyles, and prevent chronic diseases. Finally this change involves patients which are starting to use medical and health apps on their smartphones and tablets to monitor their diseases, and tools such as Patients Like Me (an online patients' community), Facebook and Twitter to share with others the same disease experience, to learn about the disease and treatments, and to find opinions on physicians, hospitals and medical centers. These new communication tools allow users to move to a kind of collaborative education and updating where news and contents (such as public health recommendations, results of the most recent clinical researches or medical guidelines) may be shared and discussed.
Okamura, Kyoko; Bernstein, Judith; Fidler, Anne T
2002-01-01
The Internet has become a major source of health information for women, but information placed on the World Wide Web does not routinely undergo a peer review process before dissemination. In this study, we present an analysis of 197 infertility-related Web sites for quality and accountability, using JAMA's minimal core standards for responsible print. Only 2% of the web sites analyzed met all four recommended standards, and 50.8% failed to report any of the four. Commercial web sites were more likely to fail to meet minimum standards (71.2%) than those with educational (46.8%) or supportive (29.8%) elements. Web sites with educational and informational components were most common (70.6%), followed by commercial sites (52.8%) and sites that offered a forum for infertility support and activism (28.9%). Internet resources available to infertile patients are at best variable. The current state of infertility-related materials on the World Wide Web offers unprecedented opportunities to improve services to a growing number of e-health users. Because of variations in quality of site content, women's health clinicians must assume responsibility for a new role as information monitor. This study provides assessment tools clinicians can apply and share with clients.
ERIC Educational Resources Information Center
Cirella, David
2012-01-01
A diverse group, account-based services include a wide variety of sites commonly used by patrons, including online shopping sites, social networks, photo- and video-sharing sites, banking and financial sites, government services, and cloud-based storage. Whether or not a piece of information is obtainable online must be considered when creating…
DOT National Transportation Integrated Search
2001-12-01
In this report, researchers present a review of the practices and technologies being used in Texas for incident management and traveler information exchange and sharing. Through interviews and site visits, researchers assimilated data from the Dallas...
Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells
Camp, J. Gray; Weiser, Matthew; Cocchiaro, Jordan L.; Kingsley, David M.; Furey, Terrence S.; Sheikh, Shehzad Z.; Rawls, John F.
2017-01-01
The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs) in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS) found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development and physiology. PMID:28850571
AstroBetter: A Blog and Wiki for Professional Astronomers
NASA Technical Reports Server (NTRS)
Rigby, Jane
2011-01-01
AstroBetter.com is a multi-contributor blog and wiki website designed for information sharing among professional astronomers. The goal of the site is to increase the productivity of astronomers by creating a centralized location for tips and tools of our multifaceted trade. Our content includes topics related to data reduction and analysis, general computing, writing papers and proposals, giving talks, teaching, career planning, productivity, organization, and diversity and equity in science and education. While we have several contributors, the site is intended to be community driven and we encourage everyone to publish to the wiki, submit guest posts, suggest post ideas, and to comment on blog entries. One of our primary goals is to consolidate and reduce the transient nature of the astronomy community's collective knowledge base by having an active wiki. Currently, the most common way to share astro-centric tools and tips that are not appropriate for a published paper, is to put them on an individual's website. However, the average astronomer's website will have at least four different addresses over the course of their career and only the site owner can edit the content. As a result, information on personal websites goes stale very quickly and deal links to such sites abound. It is our hope that community maintained wikis, such as the one hosted on AstroBetter, will gradually replace the personal website. In this poster we introduce the contributors to AstroBetter, show statistics about our current readership, give excerpts of some of our most popular posts and wiki entries, and show how anyone can add or edit content on the wiki. The goal of this poster is to spread the work about AstroBetter and increase our community of readers and wiki editors, because together, we can AstroBetter.
Metadata based management and sharing of distributed biomedical data
Vergara-Niedermayr, Cristobal; Liu, Peiya
2014-01-01
Biomedical research data sharing is becoming increasingly important for researchers to reuse experiments, pool expertise and validate approaches. However, there are many hurdles for data sharing, including the unwillingness to share, lack of flexible data model for providing context information, difficulty to share syntactically and semantically consistent data across distributed institutions, and high cost to provide tools to share the data. SciPort is a web-based collaborative biomedical data sharing platform to support data sharing across distributed organisations. SciPort provides a generic metadata model to flexibly customise and organise the data. To enable convenient data sharing, SciPort provides a central server based data sharing architecture with a one-click data sharing from a local server. To enable consistency, SciPort provides collaborative distributed schema management across distributed sites. To enable semantic consistency, SciPort provides semantic tagging through controlled vocabularies. SciPort is lightweight and can be easily deployed for building data sharing communities. PMID:24834105
Overview of Privacy in Social Networking Sites (SNS)
NASA Astrophysics Data System (ADS)
Powale, Pallavi I.; Bhutkar, Ganesh D.
2013-07-01
Social Networking Sites (SNS) have become an integral part of communication and life style of people in today's world. Because of the wide range of services offered by SNSs mostly for free of cost, these sites are attracting the attention of all possible Internet users. Most importantly, users from all age groups have become members of SNSs. Since many of the users are not aware of the data thefts associated with information sharing, they freely share their personal information with SNSs. Therefore, SNSs may be used for investigating users' character and social habits by familiar or even unknown persons and agencies. Such commercial and social scenario, has led to number of privacy and security threats. Though, all major issues in SNSs need to be addressed, by SNS providers, privacy of SNS users is the most crucial. And therefore, in this paper, we have focused our discussion on "privacy in SNSs". We have discussed different ways of Personally Identifiable Information (PII) leakages from SNSs, information revelation to third-party domains without user consent and privacy related threats associated with such information sharing. We expect that this comprehensive overview on privacy in SNSs will definitely help in raising user awareness about sharing data and managing their privacy with SNSs. It will also help SNS providers to rethink about their privacy policies.
NASA Astrophysics Data System (ADS)
Asati, Vivek; Bharti, Sanjay Kumar; Budhwani, Ashok Kumar
2017-04-01
The proviral insertion site in moloney murine leukemia virus (PIM) is a family of serine/threonine kinase of Ca2+-calmodulin-dependent protein kinase (CAMK) group which is responsible for the activation and regulation of cellular transcription and translation. The three isoforms of PIM kinase (PIM-1, PIM-2 and PIM-3) share high homology and functional idleness are widely expressed and involved in a variety of biological processes including cell survival, proliferation, differentiation and apoptosis. Altered expression of PIM-1 kinase correlated with hematologic malignancies and solid tumors. In the present study, atom-based 3D-QSAR, docking and virtual screening studies have been performed on a series of thiazolidine-2,4-dione derivatives as PIM-1 kinase inhibitors. 3D-QSAR and docking approach has shortlisted the most active thiazolidine-2,4-dione derivatives such as 28, 31, 33 and 35 with the incorporation of more than one structural feature in a single molecule. External validations by various parameters and molecular docking studies at the active site of PIM-1 kinase have proved the reliability of the developed 3D-QSAR model. The generated pharmacophore (AADHR.33) from 3D-QSAR study was used for screening of drug like compounds from ZINC database, where ZINC15056464 and ZINC83292944 showed potential binding affinities at the active site amino acid residues (LYS67, GLU171, ASP128 and ASP186) of PIM-1 kinase.
Huang, Tingting; Chang, Chin -Yuan; Lohman, Jeremy R.; ...
2016-10-01
Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us tomore » propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.« less
Shared Use of Physical Activity Facilities Among North Carolina Faith Communities, 2013
Edwards, Michael B.; Bocarro, Jason N.; Stein, Anna; Kanters, Michael A.; Sherman, Danielle Marie; Rhew, Lori K.; Stallings, Willona Marie; Bowen, Sarah K.
2017-01-01
Introduction Shared use of recreational facilities is a promising strategy for increasing access to places for physical activity. Little is known about shared use in faith-based settings. This study examined shared use practices and barriers in faith communities in North Carolina. Methods Faith communities in North Carolina (n = 234) completed an online survey (October–December 2013) designed to provide information about the extent and nature of shared use of recreational facilities. We used binary logistic regression to examine differences between congregations that shared use and those that did not share use. Results Most of the faith communities (82.9%) that completed the survey indicated that they share their facilities with outside individuals and organizations. Formal agreements were more common when faith communities shared indoor spaces such as gymnasiums and classroom meeting spaces than when they shared outdoor spaces such as playgrounds or athletic fields. Faith communities in the wealthiest counties were more likely to share their spaces than were faith communities in poorer counties. Faith communities in counties with the best health rankings were more likely to share facilities than faith communities in counties that had lower health rankings. The most frequently cited reasons faith communities did not share their facilities were that they did not know how to initiate the process of sharing their facilities or that no outside groups had ever asked. Conclusion Most faith communities shared their facilities for physical activity. Research is needed on the relationship between shared use and physical activity levels, including the effect of formalizing shared-use policies. PMID:28152362
Shared Use of Physical Activity Facilities Among North Carolina Faith Communities, 2013.
Hardison-Moody, Annie; Edwards, Michael B; Bocarro, Jason N; Stein, Anna; Kanters, Michael A; Sherman, Danielle Marie; Rhew, Lori K; Stallings, Willona Marie; Bowen, Sarah K
2017-02-02
Shared use of recreational facilities is a promising strategy for increasing access to places for physical activity. Little is known about shared use in faith-based settings. This study examined shared use practices and barriers in faith communities in North Carolina. Faith communities in North Carolina (n = 234) completed an online survey (October-December 2013) designed to provide information about the extent and nature of shared use of recreational facilities. We used binary logistic regression to examine differences between congregations that shared use and those that did not share use. Most of the faith communities (82.9%) that completed the survey indicated that they share their facilities with outside individuals and organizations. Formal agreements were more common when faith communities shared indoor spaces such as gymnasiums and classroom meeting spaces than when they shared outdoor spaces such as playgrounds or athletic fields. Faith communities in the wealthiest counties were more likely to share their spaces than were faith communities in poorer counties. Faith communities in counties with the best health rankings were more likely to share facilities than faith communities in counties that had lower health rankings. The most frequently cited reasons faith communities did not share their facilities were that they did not know how to initiate the process of sharing their facilities or that no outside groups had ever asked. Most faith communities shared their facilities for physical activity. Research is needed on the relationship between shared use and physical activity levels, including the effect of formalizing shared-use policies.
Plasma membrane calcium ATPases and related disorders.
Giacomello, Marta; De Mario, Agnese; Scarlatti, Chiara; Primerano, Simona; Carafoli, Ernesto
2013-03-01
The plasma membrane Ca(2+) ATPases (PMCA pumps) cooperate with other transport systems in the plasma membrane and in the organelles in the regulation of cell Ca(2+). They have high Ca(2+) affinity and are thus the fine tuners of cytosolic Ca(2+). They belong to the superfamily of P-type ATPases: their four basic isoforms share the essential properties of the reaction cycle and the general membrane topography motif of 10 transmembrane domains and three large cytosolic units. However they also differ in other important properties, e.g., tissue distribution and regulatory mechanisms. Their chief regulator is calmodulin, that removes their C-terminal cytosolic tail from autoinhibitory binding sites next to the active site of the pump, restoring activity. The number of pump isoforms is increased to over 30 by alternative splicing of the transcripts at a N-terminal site (site A) and at site C within the C-terminal calmodulin binding domain: the splice variants are tissue specific and developmentally regulated. The importance of PMCAs in the maintenance of cellular Ca(2+) homeostasis is underlined by the disease phenotypes, genetic or acquired, caused by their malfunction. Non-genetic PMCA deficiencies have long been considered possible causative factors in disease conditions as important as cancer, hypertension, or neurodegeneration. Those of genetic origin are better characterized: some have now been discovered in humans as well. They concern all four PMCA isoforms, and range from cardiac dysfunctions, to deafness, to hypertension, to cerebellar ataxia. Copyright © 2012 Elsevier Ltd. All rights reserved.
The benefits, risks and costs of privacy: patient preferences and willingness to pay.
Trachtenbarg, David E; Asche, Carl; Ramsahai, Shweta; Duling, Joy; Ren, Jinma
2017-05-01
Multiple surveys show that patients want medical privacy; however, there are costs to maintaining privacy. There are also risks if information is not shared. A review of previous surveys found that most surveys asked questions about patient's privacy concerns and willingness to share their medical information. We found only one study that asked about sharing medical information for better care and no survey that asked patients about the risk, cost or comparison between medical privacy and privacy in other areas. To fill this gap, we designed a survey to: (1) compare medical privacy preferences to privacy preferences in other areas; (2) measure willingness to pay the cost of additional privacy measures; and (3) measure willingness to accept the risks of not sharing information. A total of 834 patients attending physician offices at 14 sites completed all or part of an anonymous questionnaire. Over 95% of patients were willing to share all their medical information with their treating physicians. There was no difference in willingness to share between primary care and specialty sites including psychiatry and an HIV clinic. In our survey, there was no difference in sharing preference between standard medical information and information with additional legal protections including genetic testing, drug/alcohol treatment and HIV results. Medical privacy was ranked lower than sharing social security and credit card numbers, but was deemed more private than other information including tax returns and handgun purchases. There was no statistical difference for any questions by site except for HIV/AIDS clinic patients ranking privacy of the medical record more important than reducing high medical costs and risk of medical errors (p < .05). Most patients were willing to spend a modest amount of additional time for privacy, but few were willing to pay more for additional medical privacy. Most patients were unwilling to take on additional risks to keep medical information hidden. Patients were very willing to share medical information with their providers. They were able to see the importance of sharing medical information to provide the best possible care. They were unwilling to hide information from providers if there was increased medical risk. Patients were willing to spend additional time for privacy, but most were unwilling to spend extra money. Sixty-eight percent of patients favored reducing medical costs over privacy.
NASA Technical Reports Server (NTRS)
2004-01-01
KENNEDY SPACE CENTER, FLA. KSC Director Jim Kennedy (center) makes a presentation to NASA and other officials about the benefits of locating NASAs new Shared Services Center in the Central Florida Research Park, near Orlando. Central Florida leaders are proposing the research park as the site for the NASA Shared Services Center. The center would centralize NASAs payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
Digital Discernment: An E-Commerce Web Site Evaluation Tool
ERIC Educational Resources Information Center
Sigman, Betsy Page; Boston, Brian J.
2013-01-01
Students entering the business workforce today may well share some responsibility for developing, revising, or evaluating their company's Web site. They may lack the experience, however, to critique their employer's Web presence effectively. The purpose of developing Digital Discernment, an e-commerce Web site evaluation tool, was to prepare…
Site-Based Management: Avoiding Disaster While Sharing Decision Making.
ERIC Educational Resources Information Center
Sorenson, Larry Dean
This paper argues that many site-based management practices do not represent true empowerment and are not founded on a consensual framework of values, goals, and priorities developed by educational stakeholders. In addition, they often lack clearly stated operating principles. The paper distinguishes between site-based management (SBM) and…
Network cyberinfrastructure as a shared platform to support multi-site research
USDA-ARS?s Scientific Manuscript database
Multi-site research across the Long-term Agroecosystem Research (LTAR) network requires access to data and information. We present some existing examples where you can get data from across the network and summarize the rich inventory of measurements taken across LTAR sites. But data management suppo...
Contingencies of self-worth and social-networking-site behavior.
Stefanone, Michael A; Lackaff, Derek; Rosen, Devan
2011-01-01
Social-networking sites like Facebook enable people to share a range of personal information with expansive groups of "friends." With the growing popularity of media sharing online, many questions remain regarding antecedent conditions for this behavior. Contingencies of self-worth afford a more nuanced approach to variable traits that affect self-esteem, and may help explain online behavior. A total of 311 participants completed an online survey measuring such contingencies and typical behaviors on Facebook. First, exploratory factor analyses revealed an underlying structure to the seven dimensions of self-worth. Public-based contingencies explained online photo sharing (β = 0.158, p < 0.01), while private-based contingencies demonstrated a negative relationship with time online (β = -0.186, p < 0.001). Finally, the appearance contingency for self-worth had the strongest relationship with the intensity of online photo sharing (β = 0.242), although no relationship was evident for time spent managing profiles.
A systematic review of functional donor-site morbidity after latissimus dorsi muscle transfer.
Lee, Kyeong-Tae; Mun, Goo-Hyun
2014-08-01
The authors performed a comprehensive literature review regarding functional impairment after latissimus dorsi muscle transfer, to investigate functional changes in the donor site and the potential impact on patients' daily lives. The PubMed database was searched for articles regarding functional donor-site morbidity following latissimus dorsi muscle flap harvest. Articles discussing the thoracodorsal artery perforator flap, which shares the same donor sites with the latissimus dorsi muscle flap, were also included. Functional morbidity was analyzed based on questionnaire of subjective symptoms, Disabilities of the Arm, Shoulder and Hand questionnaire, shoulder range of motion, and shoulder strength. Twenty-two articles representing 719 cases in 644 patients were reviewed, including seven prospective and 15 retrospective cohort studies. As a questionnaire summary from eight articles, 94 of 232 patients (41 percent) experienced any kind of discomfort at the donor site. In the Disabilities of the Arm, Shoulder and Hand questionnaire from seven articles, little difficulty in daily activities but significant difficulties in sports and art activities were observed. Nine of 13 articles reported some limitations of shoulder motion, particularly during the early postoperative period, and four other articles detected little limitation. Eight of 12 articles reported some shoulder strength weakness over time, and shoulder extension, adduction, and internal rotation were commonly involved. The muscle-sparing latissimus dorsi and thoracodorsal artery perforator flaps showed low functional morbidity. Functional impairment of the shoulder could develop after latissimus dorsi muscle flap transfer. Knowledge of the flap's functional morbidity will allow surgeons to inform patients regarding donor-site expectations and to accomplish better surgical outcomes.
Gélin, Pauline; Fauvelot, Cécile; Mehn, Vincent; Bureau, Sophie; Rouzé, Héloïse; Magalon, Hélène
2017-01-01
The scleractinian coral Pocillopora damicornis type β is known to present a mixed reproduction mode: through sexual reproduction, new genotypes are created, while asexual reproduction insures their propagation. In order to investigate the relative proportion of each reproduction mode in P. damicornis type β populations from Reunion Island, Indian Ocean, clonal propagation along the west coast was assessed through four sampling sites with increasing geographical distance between sites. Coral colonies were sampled either exhaustively, randomly or haphazardly within each site, and genotypic diversity was assessed using 13 microsatellite loci over a total of 510 P. damicornis type β determined a posteriori from their mtDNA haplotype (a 840 bp sequenced fragment of the Open Reading Frame). Overall, 47% of all the sampled colonies presented the same multi-locus genotype (MLG), a superclone, suggesting that asexual propagation is extremely important in Reunion Island. Within each site, numerous MLGs were shared by several colonies, suggesting local clonal propagation through fragmentation. Moreover, some of these MLGs were found to be shared among several sites located 40 km apart. While asexual reproduction by fragmentation seems unlikely over long distances, our results suggest a production of parthenogenetic larvae. Despite shared MLGs, two differentiated clusters were enclosed among populations of the west coast of Reunion Island, revealing the necessity to set up appropriate managing strategies at a local scale.
Huesch, Marco; Chetlen, Alison; Segel, Joel; Schetter, Susann
2017-06-09
The most popular social networking site in the United States is Facebook, an online forum where circles of friends create, share, and interact with each other's content in a nonpublic way. Our objectives were to understand (1) the most commonly used terms and phrases relating to breast cancer screening, (2) the most commonly shared website links that other women interacted with, and (3) the most commonly shared website links, by age groups. We used a novel proprietary tool from Facebook to analyze all of the more than 1.7 million unique interactions (comments on stories, reshares, and emoji reactions) and stories associated with breast cancer screening keywords that were generated by more than 1.1 million unique female Facebook users over the 1 month between November 15 and December 15, 2016. We report frequency distributions of the most popular shared Web content by age group and keywords. On average, each of 59,000 unique stories during the month was reshared 1.5 times, commented on nearly 8 times, and reacted to more than 20 times by other users. Posted stories were most often authored by women aged 45-54 years. Users shared, reshared, commented on, and reacted to website links predominantly to e-commerce sites (12,200/1.7 million, 36% of all the most popular links), celebrity news (n=8800, 26%), and major advocacy organizations (n=4900, 15%; almost all accounted for by the American Cancer Society breast cancer site). On Facebook, women shared and reacted to links to commercial and informative websites regarding breast cancer and screening. This information could inform patient outreach regarding breast cancer screening, indirectly through better understanding of key issues, and directly through understanding avenues for paid messaging to women authoring and reacting to content in this space. ©Marco Huesch, Alison Chetlen, Joel Segel, Susann Schetter. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.06.2017.
Chetlen, Alison; Segel, Joel; Schetter, Susann
2017-01-01
Background The most popular social networking site in the United States is Facebook, an online forum where circles of friends create, share, and interact with each other’s content in a nonpublic way. Objective Our objectives were to understand (1) the most commonly used terms and phrases relating to breast cancer screening, (2) the most commonly shared website links that other women interacted with, and (3) the most commonly shared website links, by age groups. Methods We used a novel proprietary tool from Facebook to analyze all of the more than 1.7 million unique interactions (comments on stories, reshares, and emoji reactions) and stories associated with breast cancer screening keywords that were generated by more than 1.1 million unique female Facebook users over the 1 month between November 15 and December 15, 2016. We report frequency distributions of the most popular shared Web content by age group and keywords. Results On average, each of 59,000 unique stories during the month was reshared 1.5 times, commented on nearly 8 times, and reacted to more than 20 times by other users. Posted stories were most often authored by women aged 45-54 years. Users shared, reshared, commented on, and reacted to website links predominantly to e-commerce sites (12,200/1.7 million, 36% of all the most popular links), celebrity news (n=8800, 26%), and major advocacy organizations (n=4900, 15%; almost all accounted for by the American Cancer Society breast cancer site). Conclusions On Facebook, women shared and reacted to links to commercial and informative websites regarding breast cancer and screening. This information could inform patient outreach regarding breast cancer screening, indirectly through better understanding of key issues, and directly through understanding avenues for paid messaging to women authoring and reacting to content in this space. PMID:28600279
Skala, Wolfgang; Utzschneider, Daniel T; Magdolen, Viktor; Debela, Mekdes; Guo, Shihui; Craik, Charles S; Brandstetter, Hans; Goettig, Peter
2014-12-05
Human kallikrein-related peptidase 2 (KLK2) is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the "classical" KLKs 1-3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 Å crystal structures of two KLK2-small molecule inhibitor complexes. In both structures discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn(2+) concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn(2+), which located the Zn(2+) binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family the 99-, 148-, and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Skala, Wolfgang; Utzschneider, Daniel T.; Magdolen, Viktor; Debela, Mekdes; Guo, Shihui; Craik, Charles S.; Brandstetter, Hans; Goettig, Peter
2014-01-01
Human kallikrein-related peptidase 2 (KLK2) is a tryptic serine protease predominantly expressed in prostatic tissue and secreted into prostatic fluid, a major component of seminal fluid. Most likely it activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction. KLK2 belongs to the “classical” KLKs 1–3, which share an extended 99- or kallikrein loop near their non-primed substrate binding site. Here, we report the 1.9 Å crystal structures of two KLK2-small molecule inhibitor complexes. In both structures discontinuous electron density for the 99-loop indicates that this loop is largely disordered. We provide evidence that the 99-loop is responsible for two biochemical peculiarities of KLK2, i.e. reversible inhibition by micromolar Zn2+ concentrations and permanent inactivation by autocatalytic cleavage. Indeed, several 99-loop mutants of KLK2 displayed an altered susceptibility to Zn2+, which located the Zn2+ binding site at the 99-loop/active site interface. In addition, we identified an autolysis site between residues 95e and 95f in the 99-loop, whose elimination prevented the mature enzyme from limited autolysis and irreversible inactivation. An exhaustive comparison of KLK2 with related structures revealed that in the KLK family the 99-, 148-, and 220-loop exist in open and closed conformations, allowing or preventing substrate access, which extends the concept of conformational selection in trypsin-related proteases. Taken together, our novel biochemical and structural data on KLK2 identify its 99-loop as a key player in activity regulation. PMID:25326387
The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands.
Born, Stephan; Levit, Anat; Niv, Masha Y; Meyerhof, Wolfgang; Behrens, Maik
2013-01-02
Bitter taste is a basic taste modality, required to safeguard animals against consuming toxic substances. Bitter compounds are recognized by G-protein-coupled bitter taste receptors (TAS2Rs). The human TAS2R10 responds to the toxic strychnine and numerous other compounds. The mechanism underlying the development of the broad tuning of some TAS2Rs is not understood. Using comparative modeling, site-directed mutagenesis, and functional assays, we identified residues involved in agonist-induced activation of TAS2R10, and investigated the effects of different substitutions on the receptor's response profile. Most interestingly, mutations in S85(3.29) and Q175(5.40) have differential impact on stimulation with different agonists. The fact that single point mutations lead to improved responses for some agonists and to decreased activation by others indicates that the binding site has evolved to optimally accommodate multiple agonists at the expense of reduced potency. TAS2R10 shares the agonist strychnine with TAS2R46, another broadly tuned receptor. Engineering the key determinants for TAS2R46 activation by strychnine in TAS2R10 caused a loss of response to strychnine, indicating that these paralog receptors display different strychnine-binding modes, which suggests independent acquisition of agonist specificities. This implies that the gene duplication event preceding primate speciation was accompanied by independent evolution of the strychnine-binding sites.
Mainprize, Iain L; Bean, Jordan D; Bouwman, Catrien; Kimber, Matthew S; Whitfield, Chris
2013-08-09
UDP-glucose dehydrogenase (Ugd) generates UDP-glucuronic acid, an important precursor for the production of many hexuronic acid-containing bacterial surface glycostructures. In Escherichia coli K-12, Ugd is important for biosynthesis of the environmentally regulated exopolysaccharide known as colanic acid, whereas in other E. coli isolates, the same enzyme is required for production of the constitutive group 1 capsular polysaccharides, which act as virulence determinants. Recent studies have implicated tyrosine phosphorylation in the activation of Ugd from E. coli K-12, although it is not known if this is a feature shared by bacterial Ugd proteins. The activities of Ugd from E. coli K-12 and from the group 1 capsule prototype (serotype K30) were compared. Surprisingly, for both enzymes, site-directed Tyr → Phe mutants affecting the previously proposed phosphorylation site retained similar kinetic properties to the wild-type protein. Purified Ugd from E. coli K-12 had significant levels of NAD substrate inhibition, which could be alleviated by the addition of ATP and several other nucleotide triphosphates. Mutations in a previously identified UDP-glucuronic acid allosteric binding site decreased the binding affinity of the nucleotide triphosphate. Ugd from E. coli serotype K30 was not inhibited by NAD, but its activity still increased in the presence of ATP.
Root-Bernstein, Robert; Turke, Miah; Subhramanyam, Udaya K Tiruttani; Churchill, Beth; Labahn, Joerg
2018-01-17
Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists.
OASIS: a data and software distribution service for Open Science Grid
NASA Astrophysics Data System (ADS)
Bockelman, B.; Caballero Bejar, J.; De Stefano, J.; Hover, J.; Quick, R.; Teige, S.
2014-06-01
The Open Science Grid encourages the concept of software portability: a user's scientific application should be able to run at as many sites as possible. It is necessary to provide a mechanism for OSG Virtual Organizations to install software at sites. Since its initial release, the OSG Compute Element has provided an application software installation directory to Virtual Organizations, where they can create their own sub-directory, install software into that sub-directory, and have the directory shared on the worker nodes at that site. The current model has shortcomings with regard to permissions, policies, versioning, and the lack of a unified, collective procedure or toolset for deploying software across all sites. Therefore, a new mechanism for data and software distributing is desirable. The architecture for the OSG Application Software Installation Service (OASIS) is a server-client model: the software and data are installed only once in a single place, and are automatically distributed to all client sites simultaneously. Central file distribution offers other advantages, including server-side authentication and authorization, activity records, quota management, data validation and inspection, and well-defined versioning and deletion policies. The architecture, as well as a complete analysis of the current implementation, will be described in this paper.
Superfund Redevelopment Initiative Quarterly Webinar Series
Superfund Redevelopment Initiative hosts a series of quarterly webinars on redevelopment of Superfund sites across the country that discuss the different types of reuse that are possible and share how particular sites have become reuse success stories.
ERIC Educational Resources Information Center
Chang, Chia-Jung; Liu, Chen-Chung; Shen, Yan-Jhih
2012-01-01
Collaborative web exploration, in which learners work together to explore the World Wide Web, has become a key learning activity in education contexts. Learners can use a shared computer with a shared display to explore the web together. However, such a shared-computer approach may limit active participation among learners. To address this issue,…
Bearne, Stephen L
2017-05-01
Enzymes of the enolase superfamily (ENS) are mechanistically diverse, yet share a common partial reaction (abstraction of the α-proton from a carboxylate substrate). While the catalytic machinery responsible for the deprotonation reaction has been conserved, divergent evolution has led to numerous ENS members that catalyze different overall reactions. This rich functional diversity has made the ENS an excellent model system for developing the approaches necessary to validate enzyme function. However, enzymes of the ENS also share a common bidomain structure ((β/α) 7 β-barrel domain and α+β capping domain) which makes validation of function from structural information challenging. This review presents a comparative survey of the structural data obtained over the past decade for enzymes from all seven subgroups that comprise the ENS. Of the seven ENS subgroups (enolase, mandelate racemase (MR), muconate lactonizing enzyme, β-methylaspartate ammonia lyase, d-glucarate dehydratase, d-mannonate dehydratase (ManD), and galactarate dehydratase 2), only enzymes of the MR and ManD subgroups exhibit an additional feature of structural complexity-an interdigitating loop. This loop emanates from one protomer of a homodimeric pair and penetrates into the adjacent, symmetry-related protomer to either contribute a binding determinant to the active site of the adjacent protomer, or act as a 'flying buttress' to support residues of the active site. The analysis presented in this review suggests that the interdigitating loop is the only gross structural element that permits functional distinction between ENS subgroups at the tertiary level of protein structure. Copyright © 2017 Elsevier B.V. All rights reserved.
Crystal structures of potent thiol-based inhibitors bound to carboxypeptidase B.
Adler, Marc; Bryant, Judi; Buckman, Brad; Islam, Imadul; Larsen, Brent; Finster, Silke; Kent, Lorraine; May, Karen; Mohan, Raju; Yuan, Shendong; Whitlow, Marc
2005-07-05
This paper presents the crystal structure of porcine pancreatic carboxypeptidase B (pp-CpB) in complex with a variety of thiol-based inhibitors that were developed as antagonists of activated thrombin-activatable fibrinolysis inhibitor (TAFIa). Recent studies have indicated that a selective inhibitor of TAFIa could enhance the efficacy of existing thrombolytic agents for the treatment of acute myocardial infarction, one of the most prevalent forms of heart attacks. Unfortunately, activated TAFIa rapidly degrades in solution and cannot be used for crystallographic studies. In contrast, porcine pancreatic CpB is stable at room temperature and is available from commercial sources. Both pancreatic CpB and TAFIa are zinc-based exopeptidases, and the proteins share a 47% sequence identity. The homology improves considerably in the active site where nearly all of the residues are conserved. The inhibitors used in this study were designed to mimic a C-terminal arginine residue, one of the natural substrates of TAFIa. The X-ray structures show that the thiol group chelates the active site zinc, the carboxylic acid forms a salt bridge to Arg145, and the guanidine group forms two hydrogen bonds to Asp255. A meta-substituted phenyl was introduced into our inhibitors to reduce conformational freedom. This modification vastly improved the selectivity of compounds against other exopeptidases that cleave basic residues. Comparisons between structures indicate that selectivity derives from the interaction between the guanidine group in the inhibitors and an acidic active site residue. The location of this acidic residue is not conserved in the various carboxypeptidases.
Theodorakis, Christopher W.; Bickham, John W.; Lamb, Trip; Medica, Philip A.; Lyne, T. Barrett
2001-01-01
We examined effects of radionuclide exposure at two atomic blast sites on kangaroo rats (Dipodomys merriami) at the Nevada Test Site, Nevada, USA, using genotoxicity and population genetic analyses. We assessed chromosome damage by micronucleus and flow cytometric assays and genetic variation by randomly amplified polymorphic DNA (RAPD) and mitochondrial DNA (mtDNA) analyses. The RAPD analysis showed no population structure, but mtDNA exhibited differentiation among and within populations. Genotoxicity effects were not observed when all individuals were analyzed. However, individuals with mtDNA haplotypes unique to the contaminated sites had greater chromosomal damage than contaminated-site individuals with haplotypes shared with reference sites. When interpopulation comparisons used individuals with unique haplotypes, one contaminated site had greater levels of chromosome damage than one or both of the reference sites. We hypothesize that shared-haplotype individuals are potential migrants and that unique-haplotype individuals are potential long-term residents. A parsimony approach was used to estimate the minimum number of migration events necessary to explain the haplotype distributions on a phylogenetic tree. The observed predominance of migration events into the contaminated sites supported our migration hypothesis. We conclude the atomic blast sites are ecological sinks and that immigration masks the genotoxic effects of radiation on the resident populations.
Li, Liangde; Dong, Xiaolin; Shu, Benshui; Wang, Zheng; Hu, Qiongbo; Zhong, Guohua
2014-12-01
Mitochondrial complex I is the main source of reactive oxygen species (ROS) production, but the exact site of superoxide generation or their relative contribution is not clear. This study aims to determine the function of iron-sulfur clusters (ISCU) in the initiation of ROS generation. ISCU2 and ISCU8 were cloned from Spodoptera litura which shared the conserved amino acid sequence with other insects. The expressions of the two genes were ubiquitous throughout the whole development stages and tissues. Knockdown of ISCU2 and ISCU8 resulted in the decline of the ROS, whereas rotenone and azadirachtin treatment up-regulated ROS levels by increasing mRNA expression. Furthermore, antioxidant enzyme activity of SOD and POD were up-regulated by rotenone and azadirachtin treatment and then declined after ISCU was silenced. Our results suggest the possibility that the molecules of ISCU2 and ISCU8 in complex I may serve as potential sites in the initiation of ROS generation. Copyright © 2014 Elsevier Ltd. All rights reserved.
Jones-Jordan, Lisa A.; Sinnott, Loraine T.; Graham, Nicholas D.; Cotter, Susan A.; Kleinstein, Robert N.; Manny, Ruth E.; Mutti, Donald O.; Twelker, J. Daniel; Zadnik, Karla
2014-01-01
Purpose. We determined the correlation between sibling refractive errors adjusted for shared and unique environmental factors using data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Methods. Refractive error from subjects' last study visits was used to estimate the intraclass correlation coefficient (ICC) between siblings. The correlation models used environmental factors (diopter-hours and outdoor/sports activity) assessed annually from parents by survey to adjust for shared and unique environmental exposures when estimating the heritability of refractive error (2*ICC). Results. Data from 700 families contributed to the between-sibling correlation for spherical equivalent refractive error. The mean age of the children at the last visit was 13.3 ± 0.90 years. Siblings engaged in similar amounts of near and outdoor activities (correlations ranged from 0.40–0.76). The ICC for spherical equivalent, controlling for age, sex, ethnicity, and site was 0.367 (95% confidence interval [CI] = 0.304, 0.420), with an estimated heritability of no more than 0.733. After controlling for these variables, and near and outdoor/sports activities, the resulting ICC was 0.364 (95% CI = 0.304, 0.420; estimated heritability no more than 0.728, 95% CI = 0.608, 0.850). The ICCs did not differ significantly between male–female and single sex pairs. Conclusions. Adjusting for shared family and unique, child-specific environmental factors only reduced the estimate of refractive error correlation between siblings by 0.5%. Consistent with a lack of association between myopia progression and either near work or outdoor/sports activity, substantial common environmental exposures had little effect on this correlation. Genetic effects appear to have the major role in determining the similarity of refractive error between siblings. PMID:25205866
Origins of the brain networks for advanced mathematics in expert mathematicians
Amalric, Marie; Dehaene, Stanislas
2016-01-01
The origins of human abilities for mathematics are debated: Some theories suggest that they are founded upon evolutionarily ancient brain circuits for number and space and others that they are grounded in language competence. To evaluate what brain systems underlie higher mathematics, we scanned professional mathematicians and mathematically naive subjects of equal academic standing as they evaluated the truth of advanced mathematical and nonmathematical statements. In professional mathematicians only, mathematical statements, whether in algebra, analysis, topology or geometry, activated a reproducible set of bilateral frontal, Intraparietal, and ventrolateral temporal regions. Crucially, these activations spared areas related to language and to general-knowledge semantics. Rather, mathematical judgments were related to an amplification of brain activity at sites that are activated by numbers and formulas in nonmathematicians, with a corresponding reduction in nearby face responses. The evidence suggests that high-level mathematical expertise and basic number sense share common roots in a nonlinguistic brain circuit. PMID:27071124
Origins of the brain networks for advanced mathematics in expert mathematicians.
Amalric, Marie; Dehaene, Stanislas
2016-05-03
The origins of human abilities for mathematics are debated: Some theories suggest that they are founded upon evolutionarily ancient brain circuits for number and space and others that they are grounded in language competence. To evaluate what brain systems underlie higher mathematics, we scanned professional mathematicians and mathematically naive subjects of equal academic standing as they evaluated the truth of advanced mathematical and nonmathematical statements. In professional mathematicians only, mathematical statements, whether in algebra, analysis, topology or geometry, activated a reproducible set of bilateral frontal, Intraparietal, and ventrolateral temporal regions. Crucially, these activations spared areas related to language and to general-knowledge semantics. Rather, mathematical judgments were related to an amplification of brain activity at sites that are activated by numbers and formulas in nonmathematicians, with a corresponding reduction in nearby face responses. The evidence suggests that high-level mathematical expertise and basic number sense share common roots in a nonlinguistic brain circuit.
Adapted shared reading at school for minimally verbal students with autism.
Mucchetti, Charlotte A
2013-05-01
Almost nothing is known about the capacity of minimally verbal students with autism to develop literacy skills. Shared reading is a regular practice in early education settings and is widely thought to encourage language and literacy development. There is some evidence that children with severe disabilities can be engaged in adapted shared reading activities. The current study examines the impact of teacher-led adapted shared reading activities on engagement and story comprehension in minimally verbal 5-6-year-old children with autism using a multiple baseline/alternating treatment design. Four students and three teachers participated. Teachers conducted adapted shared reading activities with modified books (visual supports, three-dimensional objects, simplified text) and used specific strategies for increasing student engagement. Student performance during adapted activities was compared to performance during standard shared reading sessions. All four students showed increased story comprehension and engagement during adapted shared reading. Average percentage of session engaged was 87%-100% during adapted sessions, compared with 41%-52% during baseline. Average number of correct responses to story comprehension questions was 4.2-4.8 out of 6 during adapted sessions compared with 1.2-2 during baseline. Visual supports, tactile objects, and specific teaching strategies offer ways for minimally verbal students to meaningfully participate in literacy activities. Future research should investigate adapted shared reading activities implemented classroom-wide as well as joint engagement, language, and literacy outcomes after using such activities over time.
A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo
Freund, Natalia T.; Horwitz, Joshua A.; Nogueira, Lilian; Sievers, Stuart A.; Scharf, Louise; Scheid, Johannes F.; Gazumyan, Anna; Liu, Cassie; Velinzon, Klara; Goldenthal, Ariel; Sanders, Rogier W.; Moore, John P.; Bjorkman, Pamela J.; Seaman, Michael S.; Walker, Bruce D.; Klein, Florian; Nussenzweig, Michel C.
2015-01-01
The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC80 value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans. PMID:26516768
Salmonella in Wild Birds Utilizing Protected and Human Impacted Habitats, Uganda.
Afema, Josephine Azikuru; Sischo, William M
2016-09-01
As human populations in Africa expand, humans encroach and modify wildlife habitats for farming, fishing, tourism, or settlement. Anthropogenic activities in shared environments may promote transmission of zoonotic pathogens between humans, domestic animals, and wildlife. Between July 2012 and February 2014, we evaluated Salmonella prevalence, serovars, genotypes, and antibiotic resistant phenotypes in resident and migratory birds utilizing human-impacted habitats in northwestern Lake Victoria and protected habitats in Queen Elisabeth National Park. Salmonella occurrence in the urban environment was assessed by sampling storm-water and wastewater from a channel that drains Kampala City into Lake Victoria. Salmonella was detected in 4.3% pooled bird fecal samples, and 57.1% of environmental samples. While birds in impacted and protected areas shared serovars, the genotypes were distinct. We found distinct strains in birds and the environment suggesting some strains in birds are host adapted, and strains circulating in the environment may not necessarily disseminate to birds. Conversely, birds in both impacted and protected areas shared strains with the urban environment, suggesting Salmonella disseminates between impacted environments and birds across sites. Overall, more strains were observed in the urban environment compared to birds, and poses risk of Salmonella reemergence in birds and transmission across species and space.
Tsark, JoAnn; Campo, Shelly; Teti, Michelle
2015-01-01
Facebook, a social network site, has been widely used among young adults. However, its potential to be used as a health promotion medium has not been fully examined. This study explored Facebook's potential for sharing human papillomavirus (HPV) vaccine information among female college students in Hawai‘i. Culturally tailored flyers and handouts were developed and distributed at one large university in Hawai‘i to recruit female college students between the age of 18 and 26 having an active Facebook account. Three focus group meetings were conducted to gather student perspectives about how information about HPV vaccine may be best shared via Facebook. We found that students believed Facebook is a good awareness tool but they needed more knowledge about the HPV vaccine to feel comfortable sharing the information. Participants preferred forwarding information to chatting about HPV. Some participants expressed concern that their Facebook friends would think the HPV vaccine information they forwarded on Facebook is spam. Participants suggested prefacing the posted HPV vaccine information with a personal note in their own words to make the message more interesting and relevant to their Facebook friends. Future interventions using Facebook to promote HPV vaccine could provide students with HPV vaccine information from credible sources and ask students to attach personal testimonials or endorsements while forwarding the information on Facebook. PMID:25954600
Zhang, Ni; Tsark, JoAnn; Campo, Shelly; Teti, Michelle
2015-04-01
Facebook, a social network site, has been widely used among young adults. However, its potential to be used as a health promotion medium has not been fully examined. This study explored Facebook's potential for sharing human papillomavirus (HPV) vaccine information among female college students in Hawai'i. Culturally tailored flyers and handouts were developed and distributed at one large university in Hawai'i to recruit female college students between the age of 18 and 26 having an active Facebook account. Three focus group meetings were conducted to gather student perspectives about how information about HPV vaccine may be best shared via Facebook. We found that students believed Facebook is a good awareness tool but they needed more knowledge about the HPV vaccine to feel comfortable sharing the information. Participants preferred forwarding information to chatting about HPV. Some participants expressed concern that their Facebook friends would think the HPV vaccine information they forwarded on Facebook is spam. Participants suggested prefacing the posted HPV vaccine information with a personal note in their own words to make the message more interesting and relevant to their Facebook friends. Future interventions using Facebook to promote HPV vaccine could provide students with HPV vaccine information from credible sources and ask students to attach personal testimonials or endorsements while forwarding the information on Facebook.
Managing data from multiple disciplines, scales, and sites to support synthesis and modeling
Olson, R. J.; Briggs, J. M.; Porter, J.H.; Mah, Grant R.; Stafford, S.G.
1999-01-01
The synthesis and modeling of ecological processes at multiple spatial and temporal scales involves bringing together and sharing data from numerous sources. This article describes a data and information system model that facilitates assembling, managing, and sharing diverse data from multiple disciplines, scales, and sites to support integrated ecological studies. Cross-site scientific-domain working groups coordinate the development of data associated with their particular scientific working group, including decisions about data requirements, data to be compiled, data formats, derived data products, and schedules across the sites. The Web-based data and information system consists of nodes for each working group plus a central node that provides data access, project information, data query, and other functionality. The approach incorporates scientists and computer experts in the working groups and provides incentives for individuals to submit documented data to the data and information system.
2004-02-19
KENNEDY SPACE CENTER, FLA. - NASA Administrator Sean O’Keefe (center) is welcomed to the Central Florida Research Park, near Orlando. Central Florida leaders are proposing the research park as the site for the new NASA Shared Services Center. The center would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
The pancreatic stellate cell: a star on the rise in pancreatic diseases
Omary, M. Bishr; Lugea, Aurelia; Lowe, Anson W.; Pandol, Stephen J.
2007-01-01
Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas of the pancreas that have exocrine function. PaSCs are regulated by autocrine and paracrine stimuli and share many features with their hepatic counterparts, studies of which have helped further our understanding of PaSC biology. Activation of PaSCs induces them to proliferate, to migrate to sites of tissue damage, to contract and possibly phagocytose, and to synthesize ECM components to promote tissue repair. Sustained activation of PaSCs has an increasingly appreciated role in the fibrosis that is associated with chronic pancreatitis and with pancreatic cancer. Therefore, understanding the biology of PaSCs offers potential therapeutic targets for the treatment and prevention of these diseases. PMID:17200706
Stromal cells in chronic inflammation and tertiary lymphoid organ formation.
Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge
2015-01-01
Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.
12 CFR 7.5010 - Shared electronic space.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Shared electronic space. 7.5010 Section 7.5010 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Electronic Activities § 7.5010 Shared electronic space. National banks that share electronic space, including...
12 CFR 7.5010 - Shared electronic space.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Shared electronic space. 7.5010 Section 7.5010 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Electronic Activities § 7.5010 Shared electronic space. National banks that share electronic space, including...
12 CFR 7.5010 - Shared electronic space.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 12 Banks and Banking 1 2011-01-01 2011-01-01 false Shared electronic space. 7.5010 Section 7.5010 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Electronic Activities § 7.5010 Shared electronic space. National banks that share electronic space, including...
12 CFR 7.5010 - Shared electronic space.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Shared electronic space. 7.5010 Section 7.5010 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Electronic Activities § 7.5010 Shared electronic space. National banks that share electronic space, including...
12 CFR 7.5010 - Shared electronic space.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Shared electronic space. 7.5010 Section 7.5010 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY BANK ACTIVITIES AND OPERATIONS Electronic Activities § 7.5010 Shared electronic space. National banks that share electronic space, including...
Federal Register 2010, 2011, 2012, 2013, 2014
2011-12-21
...] Privacy Act of 1974: Implementation of Exemptions; DOT/ALL 23-- Information Sharing Environment (ISE... titled, ``DOT/ALL 23--Information Sharing Environment (ISE) Suspicious Activity Reporting (SAR... exempts portions of the ``DOT/ALL 23--Information Sharing Environment (ISE) Suspicious Activity Reporting...
The Story Project: An Online Site for Reading and Sharing.
ERIC Educational Resources Information Center
Padgett Wheeler, Sally
This paper describes an online publishing site at Georgia Perimeter College called "The Story Project." The Web site contains more than 60 stories written by faculty members, students, administrators, staff, family, and friends, and serves to encourage student writing, create a community of writers, celebrate common and diverse past experiences,…
ERIC Educational Resources Information Center
Barrett, Joanne
2006-01-01
Social networking is one of the latest trends to evolve out of the growing online community. Social networking sites gather data submitted by members that is then stored as user profiles. The data or profiles can then be shared among the members of the site. Membership can be free or fee-based. A typical social networking site provides members…
Privacy and Social Networking Sites
ERIC Educational Resources Information Center
Timm, Dianne M.; Duven, Carolyn J.
2008-01-01
College students are relying on the Internet to make connections with other people every day. As the Internet has developed and grown, so have the capabilities for interaction. Social networking sites, a group of Web sites that provide people with the opportunity to create an online profile and to share that profile with others, are a part of…
Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara
2012-01-01
Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. PMID:22018727
Oppici, Elisa; Montioli, Riccardo; Lorenzetto, Antonio; Bianconi, Silvia; Borri Voltattorni, Carla; Cellini, Barbara
2012-01-01
Primary Hyperoxaluria Type I (PH1) is a disorder of glyoxylate metabolism caused by mutations in the human AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP) dependent enzyme. Previous investigations highlighted that, although PH1 is characterized by a significant variability in terms of enzymatic phenotype, the majority of the pathogenic variants are believed to share both structural and functional defects, as mainly revealed by data on AGT activity and expression level in crude cellular extracts. However, the knowledge of the defects of the AGT variants at a protein level is still poor. We therefore performed a side-by-side comparison between normal AGT and nine purified recombinant pathogenic variants in terms of catalytic activity, coenzyme binding mode and affinity, spectroscopic features, oligomerization, and thermal stability of both the holo- and apo-forms. Notably, we chose four variants in which the mutated residues are located in the large domain of AGT either within the active site and interacting with the coenzyme or in its proximity, and five variants in which the mutated residues are distant from the active site either in the large or in the small domain. Overall, this integrated analysis of enzymatic activity, spectroscopic and stability information is used to (i) reassess previous data obtained with crude cellular extracts, (ii) establish which form(s) (i.e. holoenzyme and/or apoenzyme) and region(s) (i.e. active site microenvironment, large and/or small domain) of the protein are affected by each mutation, and (iii) suggest the possible therapeutic approach for patients bearing the examined mutations. Copyright © 2011 Elsevier Inc. All rights reserved.
Young, Deborah R.; Spengler, John O.; Frost, Natasha; Evenson, Kelly R.; Vincent, Jeffrey M.; Whitsel, Laurie
2014-01-01
Most Americans are not sufficiently physically active, even though regular physical activity improves health and reduces the risk of many chronic diseases. Those living in rural, non-White, and lower-income communities often have insufficient access to places to be active, which can contribute to their lower level of physical activity. The shared use of school recreational facilities can provide safe and affordable places for communities. Studies suggest that challenges to shared use include additional cost, liability protection, communication among constituencies interested in sharing space, and decision-making about scheduling and space allocation. This American Heart Association policy statement has provided recommendations for federal, state, and local decision-makers to support and expand opportunities for physical activity in communities through the shared use of school spaces. PMID:24134355
Young, Deborah R; Spengler, John O; Frost, Natasha; Evenson, Kelly R; Vincent, Jeffrey M; Whitsel, Laurie
2014-09-01
Most Americans are not sufficiently physically active, even though regular physical activity improves health and reduces the risk of many chronic diseases. Those living in rural, non-White, and lower-income communities often have insufficient access to places to be active, which can contribute to their lower level of physical activity. The shared use of school recreational facilities can provide safe and affordable places for communities. Studies suggest that challenges to shared use include additional cost, liability protection, communication among constituencies interested in sharing space, and decision-making about scheduling and space allocation. This American Heart Association policy statement has provided recommendations for federal, state, and local decision-makers to support and expand opportunities for physical activity in communities through the shared use of school spaces.
Neidig, Michael L; Brown, Christina D; Light, Kenneth M; Fujimori, Danica Galonić; Nolan, Elizabeth M; Price, John C; Barr, Eric W; Bollinger, J Martin; Krebs, Carsten; Walsh, Christopher T; Solomon, Edward I
2007-11-21
The alpha-ketoglutarate (alpha-KG)-dependent oxygenases are a large and diverse class of mononuclear non-heme iron enzymes that require FeII, alpha-KG, and dioxygen for catalysis with the alpha-KG cosubstrate supplying the additional reducing equivalents for oxygen activation. While these systems exhibit a diverse array of reactivities (i.e., hydroxylation, desaturation, ring closure, etc.), they all share a common structural motif at the FeII active site, termed the 2-His-1-carboxylate facial triad. Recently, a new subclass of alpha-KG-dependent oxygenases has been identified that exhibits novel reactivity, the oxidative halogenation of unactivated carbon centers. These enzymes are also structurally unique in that they do not contain the standard facial triad, as a Cl- ligand is coordinated in place of the carboxylate. An FeII methodology involving CD, MCD, and VTVH MCD spectroscopies was applied to CytC3 to elucidate the active-site structural effects of this perturbation of the coordination sphere. A significant decrease in the affinity of FeII for apo-CytC3 was observed, supporting the necessity of the facial triad for iron coordination to form the resting site. In addition, interesting differences observed in the FeII/alpha-KG complex relative to the cognate complex in other alpha-KG-dependent oxygenases indicate the presence of a distorted 6C site with a weak water ligand. Combined with parallel studies of taurine dioxygenase and past studies of clavaminate synthase, these results define a role of the carboxylate ligand of the facial triad in stabilizing water coordination via a H-bonding interaction between the noncoordinating oxygen of the carboxylate and the coordinated water. These studies provide initial insight into the active-site features that favor chlorination by CytC3 over the hydroxylation reactions occurring in related enzymes.
76 FR 45759 - Privacy Act of 1974, as Amended
Federal Register 2010, 2011, 2012, 2013, 2014
2011-08-01
... the CFPB by providing effective, social media-based ways to share information and interact with the...: Users of social media who interact with the CFPB through various social media outlets, including but not... information that an individual shares with the CFPB through various social media sites and services. They may...
Quintessential Leadership: Leading by Design
ERIC Educational Resources Information Center
Womack, Carlise E.; Loyd, Greg
2004-01-01
This paper discusses the benefits and drawbacks of shared governance models and the ramifications of shared governance on the environment and morale of faculty, staff, and students. Effective leadership teams can be developed in all settings. With clarity of purpose and mission, communication, and sincere motivations to transition, all sites have…
ERIC Educational Resources Information Center
Read, Brock
2006-01-01
Students in the US are increasingly discovering that online socializing is far from private and that sharing personal details on social-networking Web sites, such as Facebook, can have unintended consequences. A growing number of colleges are moving to disabuse students of the notion that the Internet is their private playground and what they type…
"Heading Up the Street:" Localized Opportunities for Shared Constructions of Knowledge.
ERIC Educational Resources Information Center
Lee, Carol D.; Majors, Yolanda J.
2003-01-01
Compares linguistic and non-linguistic components of ways of speaking, being, performing, and reasoning within an urban African American secondary classroom and a midwestern African American hair salon, identifying culturally shared interactional norms that inform knowledge building across sites and analyzing how the discourse norms and structures…
47 CFR 27.1180 - The cost-sharing formula.
Code of Federal Regulations, 2012 CFR
2012-10-01
...-sharing formula. (a) An AWS licensee that relocates a BRS system with which it interferes is entitled to... this section. (b) C is the actual cost of relocating the system, and includes, but is not limited to... (design/path survey); installation; systems testing; FCC filing costs; site acquisition and civil works...
47 CFR 27.1180 - The cost-sharing formula.
Code of Federal Regulations, 2013 CFR
2013-10-01
... § 27.1180 The cost-sharing formula. (a) An AWS licensee that relocates a BRS system with which it... forth in paragraph (b) of this section. (b) C is the actual cost of relocating the system, and includes... equipment; engineering costs (design/path survey); installation; systems testing; FCC filing costs; site...
47 CFR 27.1180 - The cost-sharing formula.
Code of Federal Regulations, 2011 CFR
2011-10-01
...-sharing formula. (a) An AWS licensee that relocates a BRS system with which it interferes is entitled to... this section. (b) C is the actual cost of relocating the system, and includes, but is not limited to... (design/path survey); installation; systems testing; FCC filing costs; site acquisition and civil works...
Structure-electrochemical evolution of a Mn-rich P2 Na 2/3Fe 0.2Mn 0.8O 2 Na-ion battery cathode
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dose, Wesley M.; Sharma, Neeraj; Pramudita, James C.
The structural evolution of electrode materials directly influences the performance of sodium-ion batteries. In this work, in situ synchrotron X-ray diffraction is used to investigate the evolution of the crystal structure of a Mn-rich P2-phase Na 2/3Fe 0.2Mn 0.8O 2 cathode. A single-phase reaction takes place for the majority of the discharge–charge cycle at ~C/10, with only a short, subtle hexagonal P2 to hexagonal P2 two-phase region early in the first charge. Thus, a higher fraction of Mn compared to previous studies is demonstrated to stabilize the P2 structure at high and low potentials, with neither “Z”/OP4 phases in themore » charged state nor significant quantities of the P'2 phase in the discharged state between 1.5 and 4.2 V. Notably, sodium ions inserted during discharge are located on both available crystallographic sites, albeit with a preference for the site sharing edges with the MO 6 octahedral unit. The composition Na ~0.70Fe 0.2Mn 0.8O 2 prompts a reversible single-phase sodium redistribution between the two sites. Sodium ions vacate the site sharing faces (Naf), favoring the site sharing edges (Nae) to give a Nae/Naf site occupation of 4:1 in the discharged state. This site preference could be an intermediate state prior to the formation of the P'2 phase. Furthermore, this work shows how the Mn-rich Na 2/3Fe 0.2Mn 0.8O 2 composition and its sodium-ion distribution can minimize phase transitions during battery function, especially in the discharged state.« less
Structure-electrochemical evolution of a Mn-rich P2 Na 2/3Fe 0.2Mn 0.8O 2 Na-ion battery cathode
Dose, Wesley M.; Sharma, Neeraj; Pramudita, James C.; ...
2017-08-04
The structural evolution of electrode materials directly influences the performance of sodium-ion batteries. In this work, in situ synchrotron X-ray diffraction is used to investigate the evolution of the crystal structure of a Mn-rich P2-phase Na 2/3Fe 0.2Mn 0.8O 2 cathode. A single-phase reaction takes place for the majority of the discharge–charge cycle at ~C/10, with only a short, subtle hexagonal P2 to hexagonal P2 two-phase region early in the first charge. Thus, a higher fraction of Mn compared to previous studies is demonstrated to stabilize the P2 structure at high and low potentials, with neither “Z”/OP4 phases in themore » charged state nor significant quantities of the P'2 phase in the discharged state between 1.5 and 4.2 V. Notably, sodium ions inserted during discharge are located on both available crystallographic sites, albeit with a preference for the site sharing edges with the MO 6 octahedral unit. The composition Na ~0.70Fe 0.2Mn 0.8O 2 prompts a reversible single-phase sodium redistribution between the two sites. Sodium ions vacate the site sharing faces (Naf), favoring the site sharing edges (Nae) to give a Nae/Naf site occupation of 4:1 in the discharged state. This site preference could be an intermediate state prior to the formation of the P'2 phase. Furthermore, this work shows how the Mn-rich Na 2/3Fe 0.2Mn 0.8O 2 composition and its sodium-ion distribution can minimize phase transitions during battery function, especially in the discharged state.« less
The HydroServer Platform for Sharing Hydrologic Data
NASA Astrophysics Data System (ADS)
Tarboton, D. G.; Horsburgh, J. S.; Schreuders, K.; Maidment, D. R.; Zaslavsky, I.; Valentine, D. W.
2010-12-01
The CUAHSI Hydrologic Information System (HIS) is an internet based system that supports sharing of hydrologic data. HIS consists of databases connected using the Internet through Web services, as well as software for data discovery, access, and publication. The HIS system architecture is comprised of servers for publishing and sharing data, a centralized catalog to support cross server data discovery and a desktop client to access and analyze data. This paper focuses on HydroServer, the component developed for sharing and publishing space-time hydrologic datasets. A HydroServer is a computer server that contains a collection of databases, web services, tools, and software applications that allow data producers to store, publish, and manage the data from an experimental watershed or project site. HydroServer is designed to permit publication of data as part of a distributed national/international system, while still locally managing access to the data. We describe the HydroServer architecture and software stack, including tools for managing and publishing time series data for fixed point monitoring sites as well as spatially distributed, GIS datasets that describe a particular study area, watershed, or region. HydroServer adopts a standards based approach to data publication, relying on accepted and emerging standards for data storage and transfer. CUAHSI developed HydroServer code is free with community code development managed through the codeplex open source code repository and development system. There is some reliance on widely used commercial software for general purpose and standard data publication capability. The sharing of data in a common format is one way to stimulate interdisciplinary research and collaboration. It is anticipated that the growing, distributed network of HydroServers will facilitate cross-site comparisons and large scale studies that synthesize information from diverse settings, making the network as a whole greater than the sum of its parts in advancing hydrologic research. Details of the CUAHSI HIS can be found at http://his.cuahsi.org, and HydroServer codeplex site http://hydroserver.codeplex.com.
Brain Death and Transplant in Islamic Countries.
Altınörs, Nur; Haberal, Mehmet
2016-11-01
The aim of this study was to investigate the present status regarding brain death, its consequences, and transplant activities in Islamic countries. A thorough literature survey was conducted about transplant activities in Islamic countries, and the Turkish Ministry of Health Web site was analyzed. Expert opinions about the issue were obtained. The present status of brain death and transplant activities has shown a heterogeneous appearance in the Islamic world. Our literature survey clearly revealed that transplant is still in its early stages in many Islamic states. The legislative framework, infrastructure, and related education needs radical improvements in these states. The concept of death has to be redefined and a consensus should be reached about brain death. The pioneer countries like Turkey, Iran, and Saudi Arabia. which already have considerable experience in transplant, should share their expertise and knowledge with the countries that need guidance.
ERIC Educational Resources Information Center
Lackovic, Natasa; Crook, Charles; Cobb, Sue; Shalloe, Sally; D'Cruz, Mirabelle
2015-01-01
Background: There is much to be realised in the educational potential of national and world heritage sites. Such sites need to be supported in sharing their resources with a wide and international public, especially within formal education. Two-dimensional (2D) and three-dimensional (3D) heritage site visualisations could serve this need. Our…
Ube2V2 Is a Rosetta Stone Bridging Redox and Ubiquitin Codes, Coordinating DNA Damage Responses.
Zhao, Yi; Long, Marcus J C; Wang, Yiran; Zhang, Sheng; Aye, Yimon
2018-02-28
Posttranslational modifications (PTMs) are the lingua franca of cellular communication. Most PTMs are enzyme-orchestrated. However, the reemergence of electrophilic drugs has ushered mining of unconventional/non-enzyme-catalyzed electrophile-signaling pathways. Despite the latest impetus toward harnessing kinetically and functionally privileged cysteines for electrophilic drug design, identifying these sensors remains challenging. Herein, we designed "G-REX"-a technique that allows controlled release of reactive electrophiles in vivo. Mitigating toxicity/off-target effects associated with uncontrolled bolus exposure, G-REX tagged first-responding innate cysteines that bind electrophiles under true k cat / K m conditions. G-REX identified two allosteric ubiquitin-conjugating proteins-Ube2V1/Ube2V2-sharing a novel privileged-sensor-cysteine. This non-enzyme-catalyzed-PTM triggered responses specific to each protein. Thus, G-REX is an unbiased method to identify novel functional cysteines. Contrasting conventional active-site/off-active-site cysteine-modifications that regulate target activity, modification of Ube2V2 allosterically hyperactivated its enzymatically active binding-partner Ube2N, promoting K63-linked client ubiquitination and stimulating H2AX-dependent DNA damage response. This work establishes Ube2V2 as a Rosetta-stone bridging redox and ubiquitin codes to guard genome integrity.
Research. [SITE 2002 Section].
ERIC Educational Resources Information Center
Curtis, Reagan, Ed.
This document contains papers on instructional technology research from the SITE (Society for Information Technology & Teacher Education) 2002 conference. Topics covered include: professors share their thoughts and feelings with their students; faculty reflections on teaching online; integrating technology into preservice teacher education;…
The OOI Ocean Education Portal: Enabling the Development of Online Data Investigations
NASA Astrophysics Data System (ADS)
Lichtenwalner, C. S.; McDonnell, J. D.; Crowley, M. F.; deCharon, A.; Companion, C. J.; Glenn, S. M.
2016-02-01
The Ocean Observatories Initiative (OOI) was designed to transform ocean science, by establishing a long-term, multi-instrument, multi-platform research infrastructure at 7 arrays around the word. This unprecedented investment in ocean observation, funded by the National Science Foundation, provides a rich opportunity to reshape ocean science education as well. As part of the initial construction effort, an online Ocean Education Portal was developed to support the creation and sharing of educational resources by undergraduate faculty at universities and community colleges. The portal includes a suite of tools that enable the development of online activities for use as group or individual projects, which can be used during lectures or as homework assignments. The site includes: 1) a suite of interactive educational data visualization tools that provide simple and targeted interfaces to interact with OOI datasets; 2) a concept map builder that can be used by both educators and students to build networked diagrams of their knowledge; and 3) a "data investigation" builder that allows faculty to assemble resources into coherent learning modules. The site also includes a "vocabulary navigator" that provides a visual way to discover and learn about the OOI's infrastructure and scientific design. The site allows users to browse an ever-growing database of resources created by the community, and likewise, users can share resources they create with others. As the OOI begins its 25-year operational phase, it is our hope that faculty will be able to use the tools and investigations on the Ocean Education Portal to bring real ocean science research to their undergraduate students.
Teaching the History of Astronomy On Site in London
NASA Astrophysics Data System (ADS)
French, Linda M.
2016-01-01
In the autumn of 2014, the author had the opportunity to teach a class on the history of astronomy in England as part of a study abroad experience for students at Illinois Wesleyan University. The philosophy of the program is to use the rich cultural environment of London as a setting for active learning. In the classroom, students read and discussed selected works by Ptolemy, Copernicus, Kepler, Galileo, and Herschel. We visited Stonehenge, the Royal Greenwich Observatory, the London Science Museum, the London Monument, and the library of the Royal Astronomical Society. Lessons learned from the experience will be shared.
Action of plant proteinase inhibitors on enzymes of physiopathological importance.
Oliva, Maria Luiza V; Sampaio, Misako U
2009-09-01
Obtained from leguminous seeds, various plant proteins inhibit animal proteinases, including human, and can be considered for the development of compounds with biological activity. Inhibitors from the Bowman-Birk and plant Kunitz-type family have been characterized by proteinase specificity, primary structure and reactive site. Our group mostly studies the genus Bauhinia, mainly the species bauhinioides, rufa, ungulata and variegata. In some species, more than one inhibitor was characterized, exhibiting different properties. Although proteins from this group share high structural similarity, they present differences in proteinase inhibition, explored in studies using diverse biological models.
Construction operations for an early lunar base
NASA Technical Reports Server (NTRS)
Graf, John
1988-01-01
Six construction tasks identified as activities likely to be performed at an early lunar base are described: initializing the habitation module, preparing a landing site, transferring payload off the lander, smoothing roads, constructing the inflatable structure, and excavating for lunar oxygen production. Requirements for each task are given, and a point design capable of meeting the task requirements is described. EVA needs are listed for each task. The equipment used to perform these tasks is described. It is noted that all the tasks can be performed with three common vehicles (a rover, a truck, and an excavator) and some shared equipment.
2011-06-01
Shared Awareness and Decision Making for Small Business Topic(s) 2. Topic 1: Concepts, Theory , and Policy 1. Topic 5: Collaboration, Shared...emergencies do not have the time or the resources to collaborate on a continual basis with a large number of organizations. 3. A primary Crisis Management...Center (CMC) should be identified in advance. This is the initial site used by the Crisis Management Team and Response Teams for directing and
DOE Office of Scientific and Technical Information (OSTI.GOV)
Seed, Ian; James, Paula; Mathieson, John
2013-07-01
With decreasing budgets and increasing pressure on completing cleanup missions as quickly, safely and cost-effectively as possible, there is significant benefit to be gained from collaboration and joint efforts between organizations facing similar issues. With this in mind, the US Department of Energy (DOE) and the UK Nuclear Decommissioning Authority (NDA) have formally agreed to share information on lessons learned on the development and application of new technologies and approaches to improve the safety, cost effectiveness and schedule of the cleanup legacy wastes. To facilitate information exchange a range of tools and methodologies were established. These included tacit knowledge exchangemore » through facilitated meetings, conference calls and Site visits as well as explicit knowledge exchange through document sharing and newsletters. A DOE web-based portal has been established to capture these exchanges and add to them via discussion boards. The information exchange is operating at the Government-to-Government strategic level as well as at the Site Contractor level to address both technical and managerial topic areas. This effort has resulted in opening a dialogue and building working relationships. In some areas joint programs of work have been initiated thus saving resource and enabling the parties to leverage off one another activities. The potential benefits of high quality information exchange are significant, ranging from cost avoidance through identification of an approach to a problem that has been proven elsewhere to cost sharing and joint development of a new technology to address a common problem. The benefits in outcomes significantly outweigh the costs of the process. The applicability of the tools and methods along with the lessons learned regarding some key issues is of use to any organization that wants to improve value for money. In the waste management marketplace, there are a multitude of challenges being addressed by multiple organizations and the effective pooling and exchange of knowledge and experience can only be of benefit to all participants to help complete the cleanup mission more quickly and more cost effectively. This paper examines in detail the tools and processes used to promote information exchange and the progress made to date. It also discusses the challenges and issues involved and proposes recommendations to others who are involved in similar activities. (authors)« less
Neuroimaging Data Sharing on the Neuroinformatics Database Platform
Book, Gregory A; Stevens, Michael; Assaf, Michal; Glahn, David; Pearlson, Godfrey D
2015-01-01
We describe the Neuroinformatics Database (NiDB), an open-source database platform for archiving, analysis, and sharing of neuroimaging data. Data from the multi-site projects Autism Brain Imaging Data Exchange (ABIDE), Bipolar-Schizophrenia Network on Intermediate Phenotypes parts one and two (B-SNIP1, B-SNIP2), and Monetary Incentive Delay task (MID) are available for download from the public instance of NiDB, with more projects sharing data as it becomes available. As demonstrated by making several large datasets available, NiDB is an extensible platform appropriately suited to archive and distribute shared neuroimaging data. PMID:25888923
Messersmith, Lisa J; Adjei, Rose; Beard, Jennifer; Agyarko-Poku, Thomas; Wondergem, Peter; Falconer, Ariel; Sabin, Lora; Adu-Sarkodie, Yaw
2015-03-01
Recent evidence suggests that injecting drug use presents a new challenge to HIV prevention in West Africa. Very little is known about the HIV vulnerability of people who inject drugs (PWID) in Ghana, and no HIV prevention efforts are currently targeting PWID. Purposive sampling was used to recruit 30 (20 men and 10 women) PWID to participate in in-depth interviews in Kumasi, Ghana. Transcripts were coded and analyzed by theme. Half the men and more than half the women in this study reported sharing needles/syringes (N/S); most shared a common mixing container; and all said they shared N/S with intimate partners. Some PWID who said that they do not share N/S with other PWID, also said they routinely use N/S that they find on the ground at injecting sites or in the hospital dumpster. Nearly, all the women (9/10) and more than half the men (12/20) were currently sexually active; most had more than 1 partner in the last 6 months, but very few reported condom use. Three women said they exchanged sex for money and 3 men reported buying sex in the last year. Several PWID had no knowledge of HIV transmission through injecting. PWID in Kumasi are highly vulnerable to HIV because of N/S sharing and reuse, lack of condom use, low knowledge of HIV transmission, and lack of services. Program and policy recommendations include N/S and condom distribution, peer education, opioid substitution therapy, and training of health providers, police, and pharmacy staff.
Comparison of CCD astrolabe multi-site solar diameter observations
NASA Astrophysics Data System (ADS)
Andrei, A. H.; Boscardin, S. C.; Chollet, F.; Delmas, C.; Golbasi, O.; Jilinski, E. G.; Kiliç, H.; Laclare, F.; Morand, F.; Penna, J. L.; Reis Neto, E.
2004-11-01
Results are presented of measured variations of the photospheric solar diameter, as concurrently observed at three sites of the R2S3 (Réseau de Suivi au Sol du Rayon Solaire) consortium in 2001. Important solar flux variations appeared in that year, just after the maximum of solar activity cycle 23, make that time stretch particularly promising for a comparison of the multi-site results. The sites are those in Turkey, France and Brasil. All observations are made with similar CCD solar astrolabes, and at nearby effective wavelengths. The data reductions share algorithms, that are alike, the outcomes of which are here treated after applying a normalization correction using the Fried parameter. Since the sites are geographically quite far, atmospheric conditions are dismissed as possible causes of the large common trend found. Owing to particularities of each site, the common continuous observational period extends from April to September. The standard deviation for the daily averages is close to 0.47 arcsec for the three sites. Accordingly, the three series are smoothed by a low-pass-band Fourier filter of 150 observations (typically one month). The main common features found are a declining linear trend, of the order of 0.7 mas/day, and a relative maximum, around MJD 2120, of the order of 100 mas. Standard statistical tests endorse the correlation of the three series.
Transient Ligand Docking Sites in Cerebratulus lacteus Mini-Hemoglobin
Deng, Pengchi; Nienhaus, Karin; Palladino, Pasquale; Olson, John S.; Blouin, George; Moens, Luc; Dewilde, Sylvia; Geuens, Eva; Nienhaus, G. Ulrich
2007-01-01
The monomeric hemoglobin of the nemertean worm Cerebratulus lacteus functions as an oxygen storage protein to maintain neural activity under hypoxic conditions. It shares a large, apolar matrix tunnel with other small hemoglobins, which has been implicated as a potential ligand migration pathway. Here we explore ligand migration and binding within the distal heme pocket, to which the tunnel provides access to ligands from the outside. FTIR/TDS experiments performed at cryogenic temperatures reveal the presence of three transient ligand docking sites within the distal pocket, the primary docking site B on top of pyrrole C and secondary sites C and D. Site C is assigned to a cavity adjacent to the distal portion of the heme pocket, surrounded by the B and E helices. It has an opening to the apolar tunnel and is expected to be on the pathway for ligand entry and exit, whereas site D, circumscribed by TyrB10, GlnE7, and the CD corner, most likely is located on a side pathway of ligand migration. Flash photolysis experiments at ambient temperatures indicate that the rate-limiting step for ligand binding to CerHb is migration through the apolar channel to site C. Movement from C to B and iron-ligand bond formation involve low energy barriers and thus are very rapid processes in the wt protein. PMID:17531406
Shindo, Keisuke; Takaori-Kondo, Akifumi; Kobayashi, Masayuki; Abudu, Aierken; Fukunaga, Keiko; Uchiyama, Takashi
2003-11-07
Human immunodeficiency virus, type 1 (HIV-1) Vif protein plays an essential role in the regulation of the infectivity of HIV-1 virion. Vif functions to counteract an anti-HIV-1 cellular factor in non-permissive cells, CEM15/Apobec-3G, which shares a cytidine deaminase motif. CEM15/Apobec-3G deaminates dC to dU in the minus strand DNA of HIV-1, resulting in G to A hypermutation in the plus strand DNA. In this study, we have done the mutagenesis analysis on two cytidine deaminase motifs in CEM15/Apobec-3G and examined their antiviral functions as well as the DNA editing activity. Point mutations in the C-terminal active site such as E259Q and C291A almost completely abrogated the antiviral function, while those in the N-terminal active site such as E67Q and C100A retained this activity to a lesser extent as compared with that of the wild type. The DNA editing activities of E67Q and E259Q mutants were both retained but impaired to the same extent. This indicates that the enzymatic activity of this protein is essential but not a sole determinant of the antiviral activity. Furthermore, all the deletion mutants tested in this study lost the antiviral activity because of the loss of the activity for dimerization, suggesting that the entire protein structure is necessary for the antiviral function.
ERIC Educational Resources Information Center
Dysart, Joe
2008-01-01
Given Google's growing market share--69% of all searches by the close of 2007--it's absolutely critical for any school on the Web to ensure its site is Google-friendly. A Google-optimized site ensures that students and parents can quickly find one's district on the Web even if they don't know the address. Plus, good search optimization simply…
Unconventional Warfare in Cyberspace
2012-03-22
and social networking sites , including Facebook, he reached thousands.31 Al Qaeda’s 15 contact with possible recruits was done personally in the...next three years. DARPA noted that operations are rapidly changing with the spread of blogs, social networking sites , and media-sharing technology
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fang, Ti; Li, De-Feng; Zhou, Ning-Yi, E-mail: n.zhou@pentium.whiov.ac.cn
2011-07-08
Highlights: {yields} Application of site-directed mutagenesis to probe the active site residues of glutathione-dependent maleylpyruvate isomerase. {yields} Two conserved residues, Arg8 and Arg176, in zeta class glutathione S-transferases are critical for maleylpyruvate orientation and enolization. {yields} Arg109, found exclusively in NagL, participates in k{sub cat} regulation. {yields} The T11A mutant exhibited a significantly decreased K{sub m} value for glutathione with little impact on maleylpyruvate kinetics. {yields} The Thr11 residue appears to have significance in the evolution of glutathione S-transferase classes. -- Abstract: The maleylpyruvate isomerase NagL from Ralstonia sp. strain U2, which has been structurally characterized previously, catalyzes the isomerizationmore » of maleylpyruvate to fumarylpyruvate. It belongs to the class zeta glutathione S-transferases (GSTZs), part of the cytosolic GST family (cGSTs). In this study, site-directed mutagenesis was conducted to probe the functions of 13 putative active site residues. Steady-state kinetic information for mutants in the reduced glutathione (GSH) binding site, suggested that (a) Gln64 and Asp102 interact directly with the glutamyl moiety of glutathione, (b) Gln49 and Gln64 are involved in a potential electron-sharing network that influences the ionization of the GSH thiol. The information also suggests that (c) His38, Asn108 and Arg109 interact with the GSH glycine moiety, (d) His104 has a role in the ionization of the GSH sulfur and the stabilization of the maleyl terminal carboxyl group in the reaction intermediate and (e) Arg110 influences the electron distribution in the active site and therefore the ionization of the GSH thiolate. Kinetic data for mutants altered in the substrate-binding site imply that (a) Arg8 and Arg176 are critical for maleylpyruvate orientation and enolization, and (b) Arg109 (exclusive to NagL) participates in k{sub cat} regulation. Surprisingly, the T11A mutant had a decreased GSH K{sub m} value, whereas little impact on maleylpyruvate kinetics was observed, suggesting that this residue plays an important role in GSH binding. An evolutionary trend in this residue appears to have developed not only in prokaryotic and eukaryotic GSTZs, but also among the wider class of cGSTs.« less
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Steve Matousek (left), former Juno mission manager, and Jan Chodas, Juno project manager, both from the Jet Propulsion Laboratory in Pasadena, Calif., speak to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, Andrew Aldrin, director of Business Development and Advanced Programs for the United Launch Alliance, speaks to about 150 followers of the agency’s Twitter account during Juno Tweetup activities inside a tent at the Press Site. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Gianni M. Woods
2011-08-05
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, NASA Administrator Charles Bolden (front row center, red tie) poses for a group portrait with about 150 followers of the agency’s Twitter account during Juno Tweetup activities at the Press Site. In the background is the 525-foot-tall Vehicle Assembly Building. The tweeters are at the center for two days of prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: NASA/Gianni M. Woods
DOE Office of Scientific and Technical Information (OSTI.GOV)
Booe, Jason M.; Walker, Christopher S.; Barwell, James
Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind relatedmore » GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. Lastly, the structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.« less
Booe, Jason M.; Walker, Christopher S.; Barwell, James; ...
2015-05-14
Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind relatedmore » GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. Lastly, the structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.« less
DataONE: Survey of Earth Scientists, To Share or Not to Share Data
NASA Astrophysics Data System (ADS)
Branch, B. D.; Tenopir, C.; Allard, S.; Douglas, K.; Wu, L.; Frame, M.; Dataone-The Data Observation NetworkEarth
2010-12-01
A primary goal of the Data Observation Network for Earth (DataONE; http://dataone.org) is to ensure preservation and access to multi-scale, multi-discipline, and multi-national science data, particularly in the Earth and Environmental Sciences. As a means to measure project success and to better understand the needs of the community, we have conducted a baseline assessment of the data sharing practices and preferences of domain scientists. The survey is motivated by the understanding that improving access to the sharing of data requires changes in both technology and expectations of the scientific community. A follow-up survey conducted in the future will measure how data sharing initiatives such as DataONE have influenced attitudes and behaviors. A letter of invitation with a link to an online survey instrument was emailed to scientists. Scientists were contacted by several methods: through contacts at the universities where they work, through journal editors of science journals, and directly to biology and environmental science faculty at major U.S. universities. A total of 1329 responses were received. The overall findings from the baseline assessment demonstrate several key findings. -Data management practices vary: {56.1%of respondents did not use any metadata standard, 22.1% used a lab created metadata standard, and over half of respondents 59% (local site) and 55% (national site) mentioned that at least some of their data were available; only 42% (global) and 35% (regional site) respondents mentioned that their data were available.} -Many scientists are interested in sharing data. Over 80% of respondents agreed with the statements: {“I would use other researchers' datasets if their datasets were easily accessible.” and “I would be willing to share data across a broad group of researchers who use data in different ways.”} -There are many barriers to sharing data. The two most common barriers identified were: {Insufficient time (54%) and Lack of funding (40%)} -Some disciplines are using good data management practices: {90% of atmospheric scientists say they share data with others, and 49% of atmospheric scientists agree with the statement “Others can access my data easily”} Results will be compared with other recent surveys of data management practices, including Dryad digital repository efforts (NSF EF-0423641) and Permanent Access to the Records of Science in Europe (2010) study. Future work will seek to further investigate such findings by conducting in-depth profiles and possible personas development as an evidenced based rationale for earth scientists’ data sharing practices.
DOE Office of Scientific and Technical Information (OSTI.GOV)
McLuskey, Karen; Grewal, Jaspreet S.; Das, Debanu
Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other familiesmore » in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys 147, resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys 147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca 2+ for activity. Altogether, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms.« less
Liu, Jingwen; Cai, Weicong; Fang, Xian; Wang, Xueting; Li, Guiling
2018-04-01
Lytic viral infection and programmed cell death (PCD) are thought to represent two distinct death mechanisms in phytoplankton, unicellular photoautotrophs that drift with ocean currents. PCD (apoptosis) is mainly brought about by the activation of caspases, a protease family with unique substrate selectivity. Here, we demonstrated that virus infection induced apoptosis of marine coccolithophorid Emiliania huxleyi BOF92 involving activation of metacaspase. E. huxleyi cells exhibited cell death process akin to that of apoptosis when exposed to virus infection. We observed typical hallmarks of apoptosis including cell shrinkage, associated nuclear morphological changes and DNA fragmentation. Immunoblotting revealed that antibody against human active-caspase-3 shared epitopes with a protein of ≈ 23 kDa; whose pattern of expression correlated with the onset of cell death. Moreover, analysis on two-dimensional gel electrophoresis revealed that two spots of active caspase-3 co-migrated with the different isoelectric points. Phosphatase treatment of cytosolic extracts containing active caspases-3 showed a mobility shift, suggesting that phosphorylated form of this enzyme might be present in the extracts. Computational prediction of phosphorylation sites based on the amino acid sequence of E. huxleyi metacaspase showed multiple phosphorylated sites for serine, threonine and tyrosine residues. This is the first report showing that phosphorylation modification of metacaspase in E. huxleyi might be required for certain biochemical and morphological changes during virus induced apoptosis.
Help Central: Creating a Help Desk and Knowledge Portal in SharePoint
ERIC Educational Resources Information Center
Ennis, Lisa A.; Tims, Randy S.
2012-01-01
This article discusses the authors' implementation of Help Central, a site within the Lister Hill Library Collection on the University of Alabama-Birmingham's SharePoint server. Initially, Help Central was designed to address the inadequacies in the library's old, static HTML web-based support system, including haphazard issue reporting by staff…
Connecting Music Education and Virtual Performance Practices from YouTube
ERIC Educational Resources Information Center
Cayari, Christopher
2018-01-01
The Internet has inspired musicians to explore technologies to produce recorded music performances. Social media sites like YouTube provide spaces for musicians to share their works, and the advances of technologies that afford venues and opportunities for performers to share their crafts. As amateur Internet musicians develop practices to create…
Why Do People Share Content? Identifying Why Students Support Sharing Course Material
ERIC Educational Resources Information Center
Tromp, Gerhard Wieger; Long, Phillip D.
2013-01-01
To establish which factors predict student intentions to contribute towards an OpenCourseWare site, an online questionnaire was distributed among University of Queensland students via email. The 320 participants completed items that were based on the theory of planned behaviour and were designed to measure attitudes, subjective norms and perceived…
Can You Relate? Real-World Advice for Teens on Guys, Girls, Growing Up, and Getting Along.
ERIC Educational Resources Information Center
Fox, Annie
This book's author is the creator of an award-winning web site for teens and young adults. The Web site, Talk City's InSite, invites young people to share their questions and concerns about relationships. This book brings information from the web site onto the printed page. Based on hundreds of e-mails receive by the author, it discusses issues…
Dissecting transcription-coupled and global genomic repair in the chromatin of yeast GAL1-10 genes.
Li, Shisheng; Smerdon, Michael J
2004-04-02
Transcription-coupled repair (TCR) and global genomic repair (GGR) of UV-induced cyclobutane pyrimidine dimers were investigated in the yeast GAL1-10 genes. Both Rpb9- and Rad26-mediated TCR are confined to the transcribed strands, initiating at upstream sites approximately 100 nucleotides from the upstream activating sequence shared by the two genes. However, TCR initiation sites do not correlate with either transcription start sites or TATA boxes. Rad16-mediated GGR tightly correlates with nucleosome positioning when the genes are repressed and are slow in the nucleosome core and fast in linker DNA. Induction of transcription enhanced GGR in nucleosome core DNA, especially in the nucleosomes around and upstream of the transcription start sites. Furthermore, when the genes were induced, GGR was slower in the transcribed regions than in the upstream regions. Finally, simultaneous deletion of RAD16, RAD26, and RPB9 resulted in no detectable repair in all sites along the region analyzed. Our results suggest that (a). TCR may be initiated by a transcription activator, presumably through the loading of RNA polymerase II, rather than by transcription initiation or elongation per se; (b). TCR and nucleosome disruption-enhanced GGR are the major causes of rapid repair in regions around and upstream of transcription start sites; (c). transcription machinery may hinder access of NER factors to a DNA lesion in the absence of a transcription-repair coupling factor; and (d). other than GGR mediated by Rad16 and TCR mediated by Rad26 and Rpb9, no other nucleotide excision repair pathway exists in these RNA polymerase II-transcribed genes.
Identification of a Second Substrate-binding Site in Solute-Sodium Symporters*
Li, Zheng; Lee, Ashley S. E.; Bracher, Susanne; Jung, Heinrich; Paz, Aviv; Kumar, Jay P.; Abramson, Jeff; Quick, Matthias; Shi, Lei
2015-01-01
The structure of the sodium/galactose transporter (vSGLT), a solute-sodium symporter (SSS) from Vibrio parahaemolyticus, shares a common structural fold with LeuT of the neurotransmitter-sodium symporter family. Structural alignments between LeuT and vSGLT reveal that the crystallographically identified galactose-binding site in vSGLT is located in a more extracellular location relative to the central substrate-binding site (S1) in LeuT. Our computational analyses suggest the existence of an additional galactose-binding site in vSGLT that aligns to the S1 site of LeuT. Radiolabeled galactose saturation binding experiments indicate that, like LeuT, vSGLT can simultaneously bind two substrate molecules under equilibrium conditions. Mutating key residues in the individual substrate-binding sites reduced the molar substrate-to-protein binding stoichiometry to ∼1. In addition, the related and more experimentally tractable SSS member PutP (the Na+/proline transporter) also exhibits a binding stoichiometry of 2. Targeting residues in the proposed sites with mutations results in the reduction of the binding stoichiometry and is accompanied by severely impaired translocation of proline. Our data suggest that substrate transport by SSS members requires both substrate-binding sites, thereby implying that SSSs and neurotransmitter-sodium symporters share common mechanistic elements in substrate transport. PMID:25398883
Charbonneau, Deborah H
2016-08-01
While online communities for social support continue to grow, little is known about the state of privacy practices of health social networking sites. This article reports on a structured content analysis of privacy policies and disclosure practices for 25 online ovarian cancer communities. All of the health social networking sites in the study sample provided privacy statements to users, yet privacy practices varied considerably across the sites. The majority of sites informed users that personal information was collected about participants and shared with third parties (96%, n = 24). Furthermore, more than half of the sites (56%, n = 14) stated that cookies technology was used to track user behaviors. Despite these disclosures, only 36% (n = 9) offered opt-out choices for sharing data with third parties. In addition, very few of the sites (28%, n = 7) allowed individuals to delete their personal information. Discussions about specific security measures used to protect personal information were largely missing. Implications for privacy, confidentiality, consumer choice, and data safety in online environments are discussed. Overall, nurses and other health professionals can utilize these findings to encourage individuals seeking online support and participating in social networking sites to build awareness of privacy risks to better protect their personal health information in the digital age.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kato, T.T.; Rose, B.R.; O'Farrell, T.P.
1987-09-01
The distribution, abundance, and habitat use of the endangered blunt-nosed leopard lizard, Gambelia silus, was studied on and adjacent to Naval Petroleum Reserves No. 1 (NPR-1, Elk Hills), and No. 2 (NPR-2, Buena Vista), Kern County, CAlifornia. A total of 262 blunt-nosed leopard lizards were seen over 8 years (1979-1987) in 28 sections of NPR-1, 15 sections of NPR-2, and 10 sections adjacent to the petroleum reserves. All but one were in areas of gentle or flat relief with sparse annual ground cover. Home range size and overlap, activity patterns, and habitat use were determined from monitoring blunt-nosed leopard lizardsmore » fitted with miniature radiocollars on two study sites. Mean home range size estimated by the minimum polygon method was 2.7 acres for female blunt-nosed leopard lizards, which was significantly smaller than the 5.4 acres mean home range size for males inhabiting a major wash. The structure of the habitat affected significantly the lizards' activity and burrow use. Lizards inhabiting the wash study site were more frequently seen on the surface not associated with a burrow than lizards in the more sparsely vegetated grassland study site (63% compared with 48% of their sightings); 51.5% of the sightings for lizards in the grassland study site were associated with burrows, compared with 37.1% for lizards in the wash study site. Burrows were not shared and some burrows were used more than once (30% of burrows and 62% of burrow sightings).« less
Depupylase Dop Requires Inorganic Phosphate in the Active Site for Catalysis.
Bolten, Marcel; Vahlensieck, Christian; Lipp, Colette; Leibundgut, Marc; Ban, Nenad; Weber-Ban, Eilika
2017-03-10
Analogous to eukaryotic ubiquitination, proteins in actinobacteria can be post-translationally modified in a process referred to as pupylation, the covalent attachment of prokaryotic ubiquitin-like protein Pup to lysine side chains of the target protein via an isopeptide bond. As in eukaryotes, an opposing activity counteracts the modification by specific cleavage of the isopeptide bond formed with Pup. However, the enzymes involved in pupylation and depupylation have evolved independently of ubiquitination and are related to the family of ATP-binding and hydrolyzing carboxylate-amine ligases of the glutamine synthetase type. Furthermore, the Pup ligase PafA and the depupylase Dop share close structural and sequence homology and have a common evolutionary history despite catalyzing opposing reactions. Here, we investigate the role played by the nucleotide in the active site of the depupylase Dop using a combination of biochemical experiments and X-ray crystallographic studies. We show that, although Dop does not turn over ATP stoichiometrically with substrate, the active site nucleotide species in Dop is ADP and inorganic phosphate rather than ATP, and that non-hydrolyzable analogs of ATP cannot support the enzymatic reaction. This finding suggests that the catalytic mechanism is more similar to the mechanism of the ligase PafA than previously thought and likely involves the transient formation of a phosphorylated Pup-intermediate. Evidence is presented for a mechanism where the inorganic phosphate acts as the nucleophilic species in amide bond cleavage and implications for Dop function are discussed. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Matsuda, Makoto; Takeshita, Kohei; Kurokawa, Tatsuki; Sakata, Souhei; Suzuki, Mamoru; Yamashita, Eiki; Okamura, Yasushi; Nakagawa, Atsushi
2011-07-01
Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) has a transmembrane voltage sensor domain and a cytoplasmic region sharing similarity to the phosphatase and tensin homolog (PTEN). It dephosphorylates phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate upon membrane depolarization. The cytoplasmic region is composed of a phosphatase domain and a putative membrane interaction domain, C2. Here we determined the crystal structures of the Ci-VSP cytoplasmic region in three distinct constructs, wild-type (248-576), wild-type (236-576), and G365A mutant (248-576). The crystal structure of WT-236 and G365A-248 had the disulfide bond between the catalytic residue Cys-363 and the adjacent residue Cys-310. On the other hand, the disulfide bond was not present in the crystal structure of WT-248. These suggest the possibility that Ci-VSP is regulated by reactive oxygen species as found in PTEN. These structures also revealed that the conformation of the TI loop in the active site of the Ci-VSP cytoplasmic region was distinct from the corresponding region of PTEN; Ci-VSP has glutamic acid (Glu-411) in the TI loop, orienting toward the center of active site pocket. Mutation of Glu-411 led to acquirement of increased activity toward phosphatidylinositol 3,5-bisphosphate, suggesting that this site is required for determining substrate specificity. Our results provide the basic information of the enzymatic mechanism of Ci-VSP.
Lovering, Andrew L.; Capeness, Michael J.; Lambert, Carey; Hobley, Laura; Sockett, R. Elizabeth
2011-01-01
ABSTRACT Cyclic-di-GMP is a near-ubiquitous bacterial second messenger that is important in localized signal transmission during the control of various processes, including virulence and switching between planktonic and biofilm-based lifestyles. Cyclic-di-GMP is synthesized by GGDEF diguanylate cyclases and hydrolyzed by EAL or HD-GYP phosphodiesterases, with each functional domain often appended to distinct sensory modules. HD-GYP domain proteins have resisted structural analysis, but here we present the first structural representative of this family (1.28 Å), obtained using the unusual Bd1817 HD-GYP protein from the predatory bacterium Bdellovibrio bacteriovorus. Bd1817 lacks the active-site tyrosine present in most HD-GYP family members yet remains an excellent model of their features, sharing 48% sequence similarity with the archetype RpfG. The protein structure is highly modular and thus provides a basis for delineating domain boundaries in other stimulus-dependent homologues. Conserved residues in the HD-GYP family cluster around a binuclear metal center, which is observed complexed to a molecule of phosphate, providing information on the mode of hydroxide ion attack on substrate. The fold and active site of the HD-GYP domain are different from those of EAL proteins, and restricted access to the active-site cleft is indicative of a different mode of activity regulation. The region encompassing the GYP motif has a novel conformation and is surface exposed and available for complexation with binding partners, including GGDEF proteins. PMID:21990613
NASA Astrophysics Data System (ADS)
Piwosz, Kasia; Całkiewicz, Joanna; Gołębiewski, Marcin; Creer, Simon
2018-07-01
Pico- and nanoplanktonic protists (eukaryotic microorganisms with cell size of <3 μm and 3-20 μm, respectively) are the key component of plankton communities. However, their diversity and distribution patterns along environmental factors are still poorly recognized, largely due to their very large phylogenetic diversity that has been determined only via the application of molecular methods over the past two decades. Here, we compared diversity and composition of active communities of pico- and nanoplantonic protists from three zones of the Vistula River estuary (Gulf of Gdańsk): freshwater, mixing (salinity 3.5) and brackish (salinity 7), in four seasons, by pyrosequencing the V3-V4 fragment of 18S rRNA taxonomy marker gene libraries. Alpha diversity was the highest at the brackish site, but the OTU (Operational Taxonomic Units) richness was characteristic for specific protist groups at each site. The active protistan communities in the freshwater and mixing zones (salinity 0-3.5) were similar (sharing >72% of phylotypes) and included centric diatoms (Stephanodiscus minutulus), synurophytes from clades C, E and F, and cryptophytes. However, at salinity of 7 at the brackish site the communities were significantly different from those in freshwater/mixing zone, and showed higher contributions of Dinophyceae, Mamiellophyceae, Telonemia, and picobiliphytes. The high similarity between the freshwater and mixing site, as well as high dissimilarity of the brackish site was observed in all months, despite seasonal shifts in pico- and nanoplantonic protistan communities. Seventy five percent of the observed variability in the communities was explained by combinations of temperature, salinity, nutrients and geographical distance, indicating interplay between species sorting and mass effects in shaping the active protistan communities in the Vistula River estuary. Groups that were more active in freshwaters and the mixing zone seemed to be more affected by mass effects of mixing water masses, while those from the brackish site by environmental species sorting. Finally, we report, for the first time, presence of Radiolaria (Acantharea) from the Baltic Sea.
Vest, Joshua R; Shah, Gulzar H
2012-11-01
Resource sharing, arrangements between local health departments (LHDs) for joint programs or to share staff, is a growing occurrence. The post-9/11 influx of federal funding and new public health preparedness responsibilities dramatically increased the occurrence of these inter-LHD relationships, and several states have pursed more intrastate collaboration. This article describes the current state of resource sharing among LHDs and identifies the factors associated with resource sharing. Using the National Association of County & City Health Officials' 2010 Profile Survey, we determined the self-reported number of shared programmatic activities and the number of shared organizational functions for a sample of LHDs. Negative binomial regression models described the relationships between factors suggested by interorganizational theory and the counts of sharing activities. We examined the extent of resource sharing using 2 different count variables: (1) number of shared programmatic activities and (2) number of shared organizational functions. About one-half of all LHDs are engaged in resource sharing. The extent of sharing was lower for those serving larger populations, with city jurisdictions, or of larger size. Sharing was more extensive for state-governed LHDs, those covering multiple jurisdictions, states with centralized governance, and in instances of financial constraint. Many LHDs are engaged in a greater extent of resource sharing than others. Leaders of LHDs can work within the context of these factors to leverage resource sharing to meet their organizational needs.
Kinome Analysis of Receptor-Induced Phosphorylation in Human Natural Killer Cells
König, Sebastian; Nimtz, Manfred; Scheiter, Maxi; Ljunggren, Hans-Gustaf; Bryceson, Yenan T.; Jänsch, Lothar
2012-01-01
Background Natural killer (NK) cells contribute to the defense against infected and transformed cells through the engagement of multiple germline-encoded activation receptors. Stimulation of the Fc receptor CD16 alone is sufficient for NK cell activation, whereas other receptors, such as 2B4 (CD244) and DNAM-1 (CD226), act synergistically. After receptor engagement, protein kinases play a major role in signaling networks controlling NK cell effector functions. However, it has not been characterized systematically which of all kinases encoded by the human genome (kinome) are involved in NK cell activation. Results A kinase-selective phosphoproteome approach enabled the determination of 188 kinases expressed in human NK cells. Crosslinking of CD16 as well as 2B4 and DNAM-1 revealed a total of 313 distinct kinase phosphorylation sites on 109 different kinases. Phosphorylation sites on 21 kinases were similarly regulated after engagement of either CD16 or co-engagement of 2B4 and DNAM-1. Among those, increased phosphorylation of FYN, KCC2G (CAMK2), FES, and AAK1, as well as the reduced phosphorylation of MARK2, were reproducibly observed both after engagement of CD16 and co-engagement of 2B4 and DNAM-1. Notably, only one phosphorylation on PAK4 was differentally regulated. Conclusions The present study has identified a significant portion of the NK cell kinome and defined novel phosphorylation sites in primary lymphocytes. Regulated phosphorylations observed in the early phase of NK cell activation imply these kinases are involved in NK cell signaling. Taken together, this study suggests a largely shared signaling pathway downstream of distinct activation receptors and constitutes a valuable resource for further elucidating the regulation of NK cell effector responses. PMID:22238634
The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence
Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S.
2018-01-01
Species’ distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised recreation in areas occupied by grizzly bears. PMID:29389939
The role of human outdoor recreation in shaping patterns of grizzly bear-black bear co-occurrence.
Ladle, Andrew; Steenweg, Robin; Shepherd, Brenda; Boyce, Mark S
2018-01-01
Species' distributions are influenced by a combination of landscape variables and biotic interactions with other species, including people. Grizzly bears and black bears are sympatric, competing omnivores that also share habitats with human recreationists. By adapting models for multi-species occupancy analysis, we analyzed trail camera data from 192 trail camera locations in and around Jasper National Park, Canada to estimate grizzly bear and black bear occurrence and intensity of trail use. We documented (a) occurrence of grizzly bears and black bears relative to habitat variables (b) occurrence and intensity of use relative to competing bear species and motorised and non-motorised recreational activity, and (c) temporal overlap in activity patterns among the two bear species and recreationists. Grizzly bears were spatially separated from black bears, selecting higher elevations and locations farther from roads. Both species co-occurred with motorised and non-motorised recreation, however, grizzly bears reduced their intensity of use of sites with motorised recreation present. Black bears showed higher temporal activity overlap with recreational activity than grizzly bears, however differences in bear daily activity patterns between sites with and without motorised and non-motorised recreation were not significant. Reduced intensity of use by grizzly bears of sites where motorised recreation was present is a concern given off-road recreation is becoming increasingly popular in North America, and can negatively influence grizzly bear recovery by reducing foraging opportunities near or on trails. Camera traps and multi-species occurrence models offer non-invasive methods for identifying how habitat use by animals changes relative to sympatric species, including humans. These conclusions emphasise the need for integrated land-use planning, access management, and grizzly bear conservation efforts to consider the implications of continued access for motorised recreation in areas occupied by grizzly bears.
Allain, Fabrice; Vanpouille, Christophe; Carpentier, Mathieu; Slomianny, Marie-Christine; Durieux, Sandrine; Spik, Geneviève
2002-01-01
Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPBKKK−, a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of α4β1 and α4β7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+ subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB–GAG interaction in the chemokine-like activity of this protein. PMID:11867726
Allain, Fabrice; Vanpouille, Christophe; Carpentier, Mathieu; Slomianny, Marie-Christine; Durieux, Sandrine; Spik, Geneviève
2002-03-05
Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPB(KKK-), a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of alpha4beta1 and alpha4beta7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+ subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB-GAG interaction in the chemokine-like activity of this protein.
Molecular cloning of the pheromone biosynthesis-activating neuropeptide in Helicoverpa zea.
Davis, M T; Vakharia, V N; Henry, J; Kempe, T G; Raina, A K
1992-01-01
Pheromone biosynthesis-activating neuropeptide (PBAN) regulates sex pheromone biosynthesis in female Helicoverpa (Heliothis) zea. Two oligonucleotide probes representing two overlapping amino acid regions of PBAN were used to screen 2.5 x 10(5) recombinant plaques, and a positive recombinant clone was isolated. Sequence analysis of the isolated clone showed that the PBAN gene is interrupted after the codon encoding amino acid 14 by a 0.63-kilobase (kb) intron. Preceding the PBAN amino acid sequence is a 10-amino acid sequence containing a pentapeptide Phe-Thr-Pro-Arg-Leu, which is followed by a Gly-Arg-Arg processing site. Immediately after the PBAN amino acid sequence is a Gly-Arg processing site and a short stretch of 10 amino acids. This 10-amino acid sequence contains a repeat of the PBAN C-terminal pentapeptide Phe-Ser-Pro-Arg-Leu and is terminated by another Gly-Arg processing site. It is suggested that the PBAN gene in H. zea might carry, besides PBAN, a 7- and an 8-residue amidated peptide, which share with PBAN the core C-terminal pentapeptide Phe-(Ser or Thr)-Pro-Arg-Leu-NH2. The C-terminal pentapeptide sequence of PBAN represents the minimum sequence required for pheromonotropic activity in H. zea and also bears a high degree of homology to the pyrokinin family of insect peptides with myotropic activity. It is possible that the putative heptapeptide and octapeptide might be new members of the pyrokinin family, with pheromonotropic and/or myotropic activities. Thus, the PBAN gene products, besides affecting sexual behavior, might have broad influence on many biological processes in H. zea. Images PMID:1729680
The Minimal Replicator of Epstein-Barr Virus oriP
Yates, John L.; Camiolo, Sarah M.; Bashaw, Jacqueline M.
2000-01-01
oriP is a 1.7-kb region of the Epstein-Barr virus (EBV) chromosome that supports the replication and stable maintenance of plasmids in human cells. oriP contains two essential components, called the DS and the FR, both of which contain multiple binding sites for the EBV-encoded protein, EBNA-1. The DS appears to function as the replicator of oriP, while the FR acts in conjunction with EBNA-1 to prevent the loss of plasmids from proliferating cells. Because of EBNA-1's role in stabilizing plasmids through the FR, it has not been entirely clear to what extent EBNA-1 might be required for replication from oriP per se, and a recent study has questioned whether EBNA-1 has any direct role in replication. In the present study we found that plasmids carrying oriP required EBNA-1 to replicate efficiently even when assayed only 2 days after plasmids were introduced into the cell lines 143B and 293. Significantly, using 293 cells it was demonstrated that the plasmid-retention function of EBNA-1 and the FR did not contribute significantly to the accumulation of replicated plasmids, and the DS supported efficient EBNA-1-dependent replication in the absence of the FR. The DS contains two pairs of closely spaced EBNA-1 binding sites, and a previous study had shown that both sites within either pair are required for activity. However, it was unclear from previous work what additional sequences within the DS might be required. We found that each “half” of the DS, including a pair of closely spaced EBNA-1 binding sites, had significant replicator activity when the other half had been deleted. The only significant DNA sequences that the two halves of the DS share in common, other than EBNA-1 binding sites, is a 9-bp sequence that is present twice in the “left half” and once in the “right half.” These nonamer repeats, while not essential for activity, contributed significantly to the activity of each half of the DS. Two thymines occur at unique positions within EBNA-1 binding sites 1 and 4 at the DS and become sensitive to oxidation by permanganate when EBNA-1 binds, but mutation of each to the consensus base, adenine, actually improved the activity of each half of the DS slightly. In conclusion, the DS of oriP is an EBNA-1-dependent replicator, and its minimal active core appears to be simply two properly spaced EBNA-1 binding sites. PMID:10775587
Zhang, Min; Wei, Zhiyi; Chang, Shaojie; Teng, Maikun; Gong, Weimin
2006-04-21
A 31kDa cysteine protease, SPE31, was isolated from the seeds of a legume plant, Pachyrizhus erosus. The protein was purified, crystallized and the 3D structure solved using molecular replacement. The cDNA was obtained by RT PCR followed by amplification using mRNA isolated from the seeds of the legume plant as a template. Analysis of the cDNA sequence and the 3D structure indicated the protein to belong to the papain family. Detailed analysis of the structure revealed an unusual replacement of the conserved catalytic Cys with Gly. Replacement of another conserved residue Ala/Gly by a Phe sterically blocks the access of the substrate to the active site. A polyethyleneglycol molecule and a natural peptide fragment were bound to the surface of the active site. Asn159 was found to be glycosylated. The SPE31 cDNA sequence shares several features with P34, a protein found in soybeans, that is implicated in plant defense mechanisms as an elicitor receptor binding to syringolide. P34 has also been shown to interact with vegetative storage proteins and NADH-dependent hydroxypyruvate reductase. These roles suggest that SPE31 and P34 form a unique subfamily within the papain family. The crystal structure of SPE31 complexed with a natural peptide ligand reveals a unique active site architecture. In addition, the clear evidence of glycosylated Asn159 provides useful information towards understanding the functional mechanism of SPE31/P34.
Transcriptional regulation of the human mitochondrial peptide deformylase (PDF).
Pereira-Castro, Isabel; Costa, Luís Teixeira da; Amorim, António; Azevedo, Luisa
2012-05-18
The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formyl-methionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner. Copyright © 2012 Elsevier Inc. All rights reserved.
Structure and function of APH(4)-Ia, a hygromycin B resistance enzyme.
Stogios, Peter J; Shakya, Tushar; Evdokimova, Elena; Savchenko, Alexei; Wright, Gerard D
2011-01-21
The aminoglycoside phosphotransferase (APH) APH(4)-Ia is one of two enzymes responsible for bacterial resistance to the atypical aminoglycoside antibiotic hygromycin B (hygB). The crystal structure of APH(4)-Ia enzyme was solved in complex with hygB at 1.95 Å resolution. The APH(4)-Ia structure adapts a general two-lobe architecture shared by other APH enzymes and eukaryotic kinases, with the active site located at the interdomain cavity. The enzyme forms an extended hydrogen bond network with hygB primarily through polar and acidic side chain groups. Individual alanine substitutions of seven residues involved in hygB binding did not have significant effect on APH(4)-Ia enzymatic activity, indicating that the binding affinity is spread across a distributed network. hygB appeared as the only substrate recognized by APH(4)-Ia among the panel of 14 aminoglycoside compounds. Analysis of the active site architecture and the interaction with the hygB molecule demonstrated several unique features supporting such restricted substrate specificity. Primarily the APH(4)-Ia substrate-binding site contains a cluster of hydrophobic residues that provides a complementary surface to the twisted structure of the substrate. Similar to APH(2″) enzymes, the APH(4)-Ia is able to utilize either ATP or GTP for phosphoryl transfer. The defined structural features of APH(4)-Ia interactions with hygB and the promiscuity in regard to ATP or GTP binding could be exploited for the design of novel aminoglycoside antibiotics or inhibitors of this enzyme.
Spatial heterogeneity in human activities favors the persistence of wolves in agroecosystems.
Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad
2014-01-01
As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cooke, H.; Guenther, E; Luo, Y
2009-01-01
The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem.more » 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization.« less
Spatial Heterogeneity in Human Activities Favors the Persistence of Wolves in Agroecosystems
Ahmadi, Mohsen; López-Bao, José Vicente; Kaboli, Mohammad
2014-01-01
As human populations expand, there is increasing demand and pressure for land. Under this scenario, behavioural flexibility and adaptation become important processes leading to the persistence of large carnivores in human-dominated landscapes such as agroecosystems. A growing interest has recently emerged on the outcome of the coexistence between wolves and humans in these systems. It has been suggested that spatial heterogeneity in human activities would be a major environmental factor modulating vulnerability and persistence of this contentious species in agroecosystems. Here, we combined information from 35 den sites detected between 2011 and 2012 in agroecosystems of western Iran (Hamedan province), a set of environmental variables measured at landscape and fine spatial scales, and generalized linear models to identify patterns of den site selection by wolves in a highly-modified agroecosystem. On a landscape level, wolves selected a mixture of rangelands with scattered dry-farms on hillsides (showing a low human use) to locate their dens, avoiding areas with high densities of settlements and primary roads. On a fine spatial scale, wolves primarily excavated dens into the sides of elevated steep-slope hills with availability of water bodies in the vicinity of den sites, and wolves were relegated to dig in places with coarse-soil particles. Our results suggest that vulnerability of wolves in human-dominated landscapes could be compensated by the existence of spatial heterogeneity in human activities. Such heterogeneity would favor wolf persistence in agroecosystems favoring a land sharing model of coexistence between wolves and people. PMID:25251567
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stogios, Peter J.; Shakya, Tushar; Evdokimova, Elena
The aminoglycoside phosphotransferase (APH) APH(4)-Ia is one of two enzymes responsible for bacterial resistance to the atypical aminoglycoside antibiotic hygromycin B (hygB). The crystal structure of APH(4)-Ia enzyme was solved in complex with hygB at 1.95 {angstrom} resolution. The APH(4)-Ia structure adapts a general two-lobe architecture shared by other APH enzymes and eukaryotic kinases, with the active site located at the interdomain cavity. The enzyme forms an extended hydrogen bond network with hygB primarily through polar and acidic side chain groups. Individual alanine substitutions of seven residues involved in hygB binding did not have significant effect on APH(4)-Ia enzymatic activity,more » indicating that the binding affinity is spread across a distributed network. hygB appeared as the only substrate recognized by APH(4)-Ia among the panel of 14 aminoglycoside compounds. Analysis of the active site architecture and the interaction with the hygB molecule demonstrated several unique features supporting such restricted substrate specificity. Primarily the APH(4)-Ia substrate-binding site contains a cluster of hydrophobic residues that provides a complementary surface to the twisted structure of the substrate. Similar to APH(2{double_prime}) enzymes, the APH(4)-Ia is able to utilize either ATP or GTP for phosphoryl transfer. The defined structural features of APH(4)-Ia interactions with hygB and the promiscuity in regard to ATP or GTP binding could be exploited for the design of novel aminoglycoside antibiotics or inhibitors of this enzyme.« less
Shrivastava, Dipty; Nain, Vikrant; Sahi, Shakti; Verma, Anju; Sharma, Priyanka; Sharma, Prakash Chand; Kumar, Polumetla Ananda
2011-01-22
Resistance (R) protein recognizes molecular signature of pathogen infection and activates downstream hypersensitive response signalling in plants. R protein works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study is aimed at predicting structure of R proteins signalling domains (CC-NBS) by creating a homology model, refining and optimising the model by molecular dynamics simulation and comparing ADP and ATP binding. Based on sequence similarity with proteins of known structures, CC-NBS domains were initially modelled using CED- 4 (cell death abnormality protein) and APAF-1 (apoptotic protease activating factor) as multiple templates. The final CC-NBS structural model was built and optimized by molecular dynamic simulation for 5 nanoseconds (ns). Docking of ADP and ATP at active site shows that both ligand bind specifically with same residues and with minor difference (1 Kcal/mol) in binding energy. Sharing of binding site by ADP and ATP and low difference in their binding site makes CC-NBS suitable for working as molecular switch. Furthermore, structural superimposition elucidate that CC-NBS and CARD (caspase recruitment domains) domain of CED-4 have low RMSD value of 0.9 A° Availability of 3D structural model for both CC and NBS domains will . help in getting deeper insight in these pathogen defence genes.
Plis, Sergey M; Sarwate, Anand D; Wood, Dylan; Dieringer, Christopher; Landis, Drew; Reed, Cory; Panta, Sandeep R; Turner, Jessica A; Shoemaker, Jody M; Carter, Kim W; Thompson, Paul; Hutchison, Kent; Calhoun, Vince D
2016-01-01
The field of neuroimaging has embraced the need for sharing and collaboration. Data sharing mandates from public funding agencies and major journal publishers have spurred the development of data repositories and neuroinformatics consortia. However, efficient and effective data sharing still faces several hurdles. For example, open data sharing is on the rise but is not suitable for sensitive data that are not easily shared, such as genetics. Current approaches can be cumbersome (such as negotiating multiple data sharing agreements). There are also significant data transfer, organization and computational challenges. Centralized repositories only partially address the issues. We propose a dynamic, decentralized platform for large scale analyses called the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC). The COINSTAC solution can include data missing from central repositories, allows pooling of both open and "closed" repositories by developing privacy-preserving versions of widely-used algorithms, and incorporates the tools within an easy-to-use platform enabling distributed computation. We present an initial prototype system which we demonstrate on two multi-site data sets, without aggregating the data. In addition, by iterating across sites, the COINSTAC model enables meta-analytic solutions to converge to "pooled-data" solutions (i.e., as if the entire data were in hand). More advanced approaches such as feature generation, matrix factorization models, and preprocessing can be incorporated into such a model. In sum, COINSTAC enables access to the many currently unavailable data sets, a user friendly privacy enabled interface for decentralized analysis, and a powerful solution that complements existing data sharing solutions.
Plis, Sergey M.; Sarwate, Anand D.; Wood, Dylan; Dieringer, Christopher; Landis, Drew; Reed, Cory; Panta, Sandeep R.; Turner, Jessica A.; Shoemaker, Jody M.; Carter, Kim W.; Thompson, Paul; Hutchison, Kent; Calhoun, Vince D.
2016-01-01
The field of neuroimaging has embraced the need for sharing and collaboration. Data sharing mandates from public funding agencies and major journal publishers have spurred the development of data repositories and neuroinformatics consortia. However, efficient and effective data sharing still faces several hurdles. For example, open data sharing is on the rise but is not suitable for sensitive data that are not easily shared, such as genetics. Current approaches can be cumbersome (such as negotiating multiple data sharing agreements). There are also significant data transfer, organization and computational challenges. Centralized repositories only partially address the issues. We propose a dynamic, decentralized platform for large scale analyses called the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation (COINSTAC). The COINSTAC solution can include data missing from central repositories, allows pooling of both open and “closed” repositories by developing privacy-preserving versions of widely-used algorithms, and incorporates the tools within an easy-to-use platform enabling distributed computation. We present an initial prototype system which we demonstrate on two multi-site data sets, without aggregating the data. In addition, by iterating across sites, the COINSTAC model enables meta-analytic solutions to converge to “pooled-data” solutions (i.e., as if the entire data were in hand). More advanced approaches such as feature generation, matrix factorization models, and preprocessing can be incorporated into such a model. In sum, COINSTAC enables access to the many currently unavailable data sets, a user friendly privacy enabled interface for decentralized analysis, and a powerful solution that complements existing data sharing solutions. PMID:27594820
Peters, R; King, C Y; Ukiyama, E; Falsafi, S; Donahoe, P K; Weiss, M A
1995-04-11
SRY, a genetic "master switch" for male development in mammals, exhibits two biochemical activities: sequence-specific recognition of duplex DNA and sequence-independent binding to the sharp angles of four-way DNA junctions. Here, we distinguish between these activities by analysis of a mutant SRY associated with human sex reversal (46, XY female with pure gonadal dysgenesis). The substitution (168T in human SRY) alters a nonpolar side chain in the minor-groove DNA recognition alpha-helix of the HMG box [Haqq, C.M., King, C.-Y., Ukiyama, E., Haqq, T.N., Falsalfi, S., Donahoe, P.K., & Weiss, M.A. (1994) Science 266, 1494-1500]. The native (but not mutant) side chain inserts between specific base pairs in duplex DNA, interrupting base stacking at a site of induced DNA bending. Isotope-aided 1H-NMR spectroscopy demonstrates that analogous side-chain insertion occurs on binding of SRY to a four-way junction, establishing a shared mechanism of sequence- and structure-specific DNA binding. Although the mutant DNA-binding domain exhibits > 50-fold reduction in sequence-specific DNA recognition, near wild-type affinity for four-way junctions is retained. Our results (i) identify a shared SRY-DNA contact at a site of either induced or intrinsic DNA bending, (ii) demonstrate that this contact is not required to bind an intrinsically bent DNA target, and (iii) rationalize patterns of sequence conservation or diversity among HMG boxes. Clinical association of the I68T mutation with human sex reversal supports the hypothesis that specific DNA recognition by SRY is required for male sex determination.
Bridging the Gap - Networking Educators using Real-Time Seismic Data
NASA Astrophysics Data System (ADS)
Ortiz, A. M.; Renwald, M. D.; Baldwin, T. K.; Hall, M. K.
2004-12-01
After nearly a decade, the seismology community has made critical advances in identifying what is effective and what is needed for success in incorporating real-time seismic data in the classroom. Today's K-16 classroom teachers have many options and opportunities for incorporating short- and long-term inquiry activities for monitoring earthquakes and analyzing seismic data in their daily instruction. Through the SpiNet program, we are providing web-based tools that support educators working with real-time seismic data (http://www.scieds.com/spinet/). Our site includes a Recent Seismicity section, which allows users to share seismic data in real-time, and provides near real-time information about global seismicity. Our Activities section provides data and lessons to assist educators who wish to integrate seismology into their classroom. The Research section, currently under development, will allow educators to share general information about how they teach seismology in their classroom through a discussion board and by posting lesson plans. In addition, we are developing a user-friendly tool for students to post results of their research projects. Designing a website which targets a range of users requires a working knowledge of both user needs and website programming and design. User needs include providing a logical navigational structure and accounting for differences in browser functionality, internet access, and users' abilities. Using website development tools, such as PHP, MySQL, RDF feeds, and specialized geoscience applications, we are automating site maintenance; incorporating databases for information storage and retrieval; and providing accessibility for users with a range of skills and physical limitations. By incorporating these features, we have built a dynamic interface for a broad range of users interested in educational seismology.
Burbage, Lindsey; Gonzalez, Eloisa; Dunning, Lauren; Simon, Paul; Kuo, Tony
2014-10-01
To evaluate 18 shared-use agreements (SUAs) implemented in Los Angeles County during 2010-2012. SUAs opened school grounds and/or facilities in seven school districts to increase physical activity opportunities for under-resourced communities with high prevalence of obesity. We reviewed the extent to which SUAs addressed school district concerns about cost responsibility, sustainability, and scope. A school site and community partner survey was conducted to inform planning and to facilitate comparisons of the types and range of legal clauses (up to 16) contained in the agreements. We used geographic information systems and 2010 United States Census data to estimate the population reached and the potential benefits of the SUAs. SUAs varied in the degree to which they addressed the three categories of concerns. Eight of the 18 agreements included 13 of the 16 legal clauses. We estimate that these SUAs have the potential to reach nearly 165,000 children (ages 5-19) and more than 500,000 adults (ages 20-64) at a cost of about $0.38 per community member reached. SUAs that include legal clauses to address school concerns about factors such as vandalism, staffing and funding represent a promising strategy for increasing physical activity opportunities in under-resourced neighborhoods where the prevalence of obesity is high. Copyright © 2014 Elsevier Inc. All rights reserved.
The Value of Sharing Information: A Neural Account of Information Transmission.
Baek, Elisa C; Scholz, Christin; O'Donnell, Matthew Brook; Falk, Emily B
2017-07-01
Humans routinely share information with one another. What drives this behavior? We used neuroimaging to test an account of information selection and sharing that emphasizes inherent reward in self-reflection and connecting with other people. Participants underwent functional MRI while they considered personally reading and sharing New York Times articles. Activity in neural regions involved in positive valuation, self-related processing, and taking the perspective of others was significantly associated with decisions to select and share articles, and scaled with preferences to do so. Activity in all three sets of regions was greater when participants considered sharing articles with other people rather than selecting articles to read themselves. The findings suggest that people may consider value not only to themselves but also to others even when selecting news articles to consume personally. Further, sharing heightens activity in these pathways, in line with our proposal that humans derive value from self-reflection and connecting to others via sharing.
Ride-sharing activities in the Richmond regional planning district.
DOT National Transportation Integrated Search
1977-01-01
This report gives the results of a survey made of industries in the Richmond Regional Planning District to determine the current and expected ride-sharing activities there and the type of information deemed most useful in planning ride-sharing progra...
Access to Space Interactive Design Web Site
NASA Technical Reports Server (NTRS)
Leon, John; Cutlip, William; Hametz, Mark
2000-01-01
The Access To Space (ATS) Group at NASA's Goddard Space Flight Center (GSFC) supports the science and technology community at GSFC by facilitating frequent and affordable opportunities for access to space. Through partnerships established with access mode suppliers, the ATS Group has developed an interactive Mission Design web site. The ATS web site provides both the information and the tools necessary to assist mission planners in selecting and planning their ride to space. This includes the evaluation of single payloads vs. ride-sharing opportunities to reduce the cost of access to space. Features of this site include the following: (1) Mission Database. Our mission database contains a listing of missions ranging from proposed missions to manifested. Missions can be entered by our user community through data input tools. Data is then accessed by users through various search engines: orbit parameters, ride-share opportunities, spacecraft parameters, other mission notes, launch vehicle, and contact information. (2) Launch Vehicle Toolboxes. The launch vehicle toolboxes provide the user a full range of information on vehicle classes and individual configurations. Topics include: general information, environments, performance, payload interface, available volume, and launch sites.
Structural and mechanistic basis of proton-coupled metal ion transport in the SLC11/NRAMP family
Ehrnstorfer, Ines A.; Manatschal, Cristina; Arnold, Fabian M.; Laederach, Juerg; Dutzler, Raimund
2017-01-01
Secondary active transporters of the SLC11/NRAMP family catalyse the uptake of iron and manganese into cells. These proteins are highly conserved across all kingdoms of life and thus likely share a common transport mechanism. Here we describe the structural and functional properties of the prokaryotic SLC11 transporter EcoDMT. Its crystal structure reveals a previously unknown outward-facing state of the protein family. In proteoliposomes EcoDMT mediates proton-coupled uptake of manganese at low micromolar concentrations. Mutants of residues in the transition-metal ion-binding site severely affect transport, whereas a mutation of a conserved histidine located near this site results in metal ion transport that appears uncoupled to proton transport. Combined with previous results, our study defines the conformational changes underlying transition-metal ion transport in the SLC11 family and it provides molecular insight to its coupling to protons. PMID:28059071
2011-08-04
CAPE CANAVERAL, Fla. – At NASA’s Kennedy Space Center in Florida, about 150 followers of the agency’s Twitter account arrived at the Tweetup tent at the Press Site for two days of Juno prelaunch activities. Juno is NASA’s mission to Jupiter to study the giant planet and improve our understanding of the planet’s formation and evolution. The tweeters will share their experiences with followers through the social networking site Twitter. Attendees represent 28 states, the District of Columbia and five other countries: Canada, Finland, Norway, Spain and the United Kingdom. This is the first time NASA has invited Twitter followers to experience the launch of a planetary spacecraft. The Juno spacecraft is scheduled to launch on an Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station in Florida, Aug. 5, at 11:34 a.m. EDT. For more information, visit http://www.nasa.gov/juno. Photo credit: Jim Grossmann
Frustration Sculpts the Early Stages of Protein Folding.
Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano
2015-09-07
The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Space Sharing Between Formal and Informal Sectors In Kemang Area
NASA Astrophysics Data System (ADS)
Sihombing, Antony; Dewanti, Hafizka Chandra
2018-01-01
Sharing is a form of human activity as a social being, over resources or spaces. Humans generally define their space according to their psychological and biological needs. However, what if space sharing takes place in an urban scope? The phenomenon of space sharing happens in Kemang area done by two distinct sectors, formal and informal which both are engaged in commercial activities independently. In the study of territory and the behavior settings, the quality of environment can affect the formation of human activities in a space, occurs a phenomenon of space sharing. The researcher will discuss and present a form of the space sharing by the formal and informal sectors in a commercial area through different environmental qualities. In some circumstance, a form of space sharing can increase the value of space and obtain to a shared space, where both sectors mutually take benefits. Otherwise, it leads to an adverse impact in some others. It is clear that differences in the physical environment and social environment have an impact on the formation of space sharing and the value of space in an urban region.
Gaffron, Philine; Niemeier, Deb
2015-01-01
It has been shown that the location of schools near heavily trafficked roads can have detrimental effects on the health of children attending those schools. It is therefore desirable to screen both existing school locations and potential new school sites to assess either the need for remedial measures or suitability for the intended use. Current screening tools and public guidance on school siting are either too coarse in their spatial resolution for assessing individual sites or are highly resource intensive in their execution (e.g., through dispersion modeling). We propose a new method to help bridge the gap between these two approaches. Using this method, we also examine the public K-12 schools in the Sacramento Area Council of Governments Region, California (USA) from an environmental justice perspective. We find that PM2.5 emissions from road traffic affecting a school site are significantly positively correlated with the following metrics: percent share of Black, Hispanic and multi-ethnic students, percent share of students eligible for subsidized meals. The emissions metric correlates negatively with the schools’ Academic Performance Index, the share of White students and average parental education levels. Our PM2.5 metric also correlates with the traffic related, census tract level screening indicators from the California Communities Environmental Health Screening Tool and the tool’s tract level rate of asthma related emergency department visits. PMID:25679341
Yow, Tin T; Pera, Elena; Absalom, Nathan; Heblinski, Marika; Johnston, Graham AR; Hanrahan, Jane R; Chebib, Mary
2011-01-01
BACKGROUND G protein-coupled inwardly rectifying potassium (KIR3) channels are important proteins that regulate numerous physiological processes including excitatory responses in the CNS and the control of heart rate. Flavonoids have been shown to have significant health benefits and are a diverse source of compounds for identifying agents with novel mechanisms of action. EXPERIMENTAL APPROACH The flavonoid glycoside, naringin, was evaluated on recombinant human KIR3.1–3.4 and KIR3.1–3.2 expressed in Xenopus oocytes using two-electrode voltage clamp methods. In addition, we evaluated the activity of naringin alone and in the presence of the KIR3 channel blocker tertiapin-Q (0.5 nM, 1 nM and 3 nM) at recombinant KIR3.1–3.4 channels. Site-directed mutagenesis was used to identify amino acids within the M1–M2 loop of the KIR3.1F137S mutant channel important for naringin's activity. KEY RESULTS Naringin (100 µM) had minimal effect on uninjected oocytes but activated KIR3.1–3.4 and KIR3.1–3.2 channels. The activation by naringin of KIR3.1–3.4 channels was inhibited by tertiapin-Q in a competitive manner. An alanine-scan performed on the KIR3.1F137S mutant channel, replacing one by one aromatic amino acids within the M1–M2 loop, identified tyrosines 148 and 150 to be significantly contributing to the affinity of naringin as these mutations reduced the activity of naringin by 20- and 40-fold respectively. CONCLUSIONS AND IMPLICATIONS These results show that naringin is a direct activator of KIR3 channels and that tertiapin-Q shares an overlapping binding site on the KIR3.1–3.4. This is the first example of a ligand that activates KIR3 channels by binding to the extracellular M1–M2 linker of the channel. PMID:21391982
NASA Astrophysics Data System (ADS)
Messerotti, Mauro; Otruba, Wolfgang; Hanslmeier, Arnold
2000-06-01
The Kanzelhoehe Solar Observatory is an observing facility located in Carinthia (Austria) and operated by the Institute of Geophysics, Astrophysics and Meteorology of the Karl- Franzens University Graz. A set of instruments for solar surveillance at different wavelengths bands is continuously operated in automatic mode and is presently being upgraded to be used in supplying near-real-time solar activity indexes for space weather applications. In this frame, we tested a low-end software/hardware architecture running on the PC platform in a non-homogeneous, remotely distributed environment that allows efficient or moderately efficient application sharing at the Intranet and Extranet (i.e., Wide Area Network) levels respectively. Due to the geographical distributed of participating teams (Trieste, Italy; Kanzelhoehe and Graz, Austria), we have been using such features for collaborative remote software development and testing, data analysis and calibration, and observing run emulation from multiple sites as well. In this work, we describe the used architecture and its performances based on a series of application sharing tests we carried out to ascertain its effectiveness in real collaborative remote work, observations and data exchange. The system proved to be reliable at the Intranet level for most distributed tasks, limited to less demanding ones at the Extranet level, but quite effective in remote instrument control when real time response is not needed.
2011-11-26
CAPE CANAVERAL, Fla. – From left, former astronaut Leland Melvin, NASA associate administrator for Education; Will.i.am, entertainer and member of The Black Eyed Peas; and NASA Deputy Administrator Lori Garver share a light moment with the participants of a NASA Tweetup in a tent set up at NASA Kennedy Space Center's Press Site in Florida during prelaunch activities for the agency’s Mars Science Laboratory (MSL) launch. Participants in the Tweetup are given the opportunity to listen to agency briefings, tour locations on the center normally off limits to visitors, and get a close-up view of Space Launch Complex-41 on Cape Canaveral Air Force Station. The tweeters will share their experiences with followers through the social networking site Twitter. The MSL mission will pioneer precision landing technology and a sky-crane touchdown to place a car-sized rover, Curiosity, near the foot of a mountain inside Gale Crater on Aug. 6, 2012. During a nearly two-year prime mission after landing, the rover will investigate whether the region has ever offered conditions favorable for microbial life, including the chemical ingredients for life. Liftoff of MSL aboard a United Launch Alliance Atlas V rocket from pad 41 is planned during a launch window which extends from 10:02 a.m. to 11:45 a.m. EST on Nov. 26. For more information, visit http://www.nasa.gov/msl. Photo credit: NASA/Frankie Martin
Turke, Miah; Subhramanyam, Udaya K. Tiruttani; Churchill, Beth; Labahn, Joerg
2018-01-01
Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whether opioid receptors may have an equivalent extracellular, allosteric adrenergic binding site that has similar enhancing effects on opioid binding. Comparison of adrenergic and opioid receptor sequences revealed that these receptors share very significant regions of similarity, particularly in some of the extracellular and transmembrane regions associated with adrenergic binding in the adrenergic receptors. Five of these shared regions from the mu opioid receptor (muOPR) were synthesized as peptides and tested for binding to adrenergic, opioid and control compounds using ultraviolet spectroscopy. Adrenergic compounds bound to several of these muOPR peptides with low micromolar affinity while acetylcholine, histamine and various adrenergic antagonists did not. Similar studies were then conducted with purified, intact muOPR with similar results. Combinations of epinephrine with methionine enkephalin or morphine increased the binding of both by about half a log unit. These results suggest that muOPR may be allosterically enhanced by adrenergic agonists. PMID:29342106
X-ray structure of imidazolonepropionase from Agrobacterium tumefaciens at 1.87 Å resolution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tyagi, Rajiv; Kumaran, Desigan; Burley, Stephen K.
2010-01-12
Histidine degradation in Agrobacterium tumefaciens involves four enzymes, including histidase (EC 4.3.1.3), urocanase (EC 4.2.1.49), imidazolonepropionase (EC 3.5.2.7), and N-formylglutamate amidohydrolase (EC 3.5.3.8). The third enzyme of the pathway, imidazolone-propionase, a 45.6 kDa protein, catalyzes conversion of imidazolone-5-propanoate to N-forminio-L-glutamate. Initial studies of the role of imidazolonepropionase in histidine degradation were published in 1953. Subsequent publications have been limited to enzyme kinetics, crystallization, and a recently reported structure determination. The imidazolonepropionases are members of metallodepenent-hydrolases (or amidohydroase) superfamily, which includs ureases, adenosine deaminases, phosphotriesterases, dihydroorotases, allantoinases, hydantoinases, adenine and cytosine deaminases, imidazolonepropionases, aryldial-kylphosphatases, chlorohydrolases, and formylmethanofuran dehydroases. Proteins belonging tomore » this large group share a common three-dimensional structural motif (an eightfold {alpha}/{beta} or TIM barrel) with similar active sites. Most superfamily members also share a conserved metal binding site, involving four histidine residues and one aspartic acid. Imidazolonepropionase is one of the targets selected for X-ray crystallpgrahpic structure determination by the New York Structural GenomiX Research Consortium (NYSGXRC) Target ID: 9252b to correlate the structure function relationship of poorly studied by important enzyme. Here they report the crystal structure of imidazolonepropionase from Agrobacterium tumefaciens determined at 1.87 {angstrom} resolution.« less
Wu, Shijin; Li, Yuan; Wang, Penghua; Zhong, Li; Qiu, Lequan; Chen, Jianmeng
2016-04-01
The environmental risk of fluoride and chloride pollution is pronounced in soils adjacent to solar photovoltaic sites. The elevated levels of fluoride and chloride in these soils have had significant impacts on the population size and overall biological activity of the soil microbial communities. The microbial community also plays an essential role in remediation of these soils. Questions remain as to how the fluoride and chloride contamination and subsequent remediation at these sites have impacted the population structure of the soil microbial communities. We analyzed the microbial communities in soils collected from close to a solar photovoltaic enterprise by pyrosequencing of the 16S rRNA tag. In addition, we used multivariate statistics to identity the relationships shared between sequence diversity and heterogeneity in the soil environment. The overall microbial communities were surprisingly diverse, harboring a wide variety of taxa and sharing significant correlations with different degrees of fluoride and chloride contamination. The contaminated soils harbored abundant bacteria that were probably resistant to the high acidity, high fluoride and chloride concentration, and high osmotic pressure environment. The dominant genera were Sphingomonas, Subgroup_6_norank, Clostridium sensu stricto, Nitrospira, Rhizomicrobium, and Acidithiobacillus. The results of this study provide new information regarding a previously uncharacterized ecosystem and show the value of high-throughput sequencing in the study of complex ecosystems.
The Function of Neuroendocrine Cells in Prostate Cancer
2013-04-01
integration site. We then performed deep sequencing and aligned reads to the genome. Our analysis revealed that both histological phenotypes are derived from...lentiviral integration site analysis . (B) Laser capture microdissection was performed on individual glands containing both squamous and...lentiviral integration site analysis . LTR: long terminal repeat (viral DNA), PCR: polymerase chain reaction. (D) Venn diagrams depict shared lentiviral
Responding to Big Data in the Art Education Classroom: Affordances and Problematics
ERIC Educational Resources Information Center
Duncum, Paul
2018-01-01
The article raises questions about the use in art education classrooms of social networking sites like Facebook and image sharing sites like YouTube that rely upon the ability of Big Data to aggregate large amounts of data, including data on students. The article also offers suggestions for the responsible use of these sites. Many youth are using…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fang, Evandro Fei; Wong, Jack Ho; Bah, Clara Shui Fern
Here we report for the first time of a new Kunitz-type trypsin inhibitor (termed BvvTI) from seeds of the Camel's foot tree, Bauhinia variegata var. variegata. BvvTI shares the same reactive site residues (Arg, Ser) and exhibits a homology of N-terminal amino acid sequence to other Bauhinia protease inhibitors. The trypsin inhibitory activity (K{sub i}, 0.1 x 10{sup -9} M) of BvvTI ranks the highest among them. Besides anti-HIV-1 reverse transcriptase activity, BvvTI could significantly inhibit the proliferation of nasopharyngeal cancer CNE-1 cells in a selective way. This may partially be contributed by its induction of cytokines and apoptotic bodies.more » These results unveil potential medicinal applications of BvvTI.« less
Structure of a pectin methylesterase from Yersinia enterocolitica.
Boraston, Alisdair B; Abbott, D Wade
2012-02-01
Pectin methylesterases (PMEs) are family 8 carbohydrate esterases (CE8s) which remove the methyl group from methylesterified galacturonic acid (GalA) residues within pectin. Although the role of pectinases such as PMEs within dedicated phytopathogens has been well established, the significance of homologous enzymes found within the genomes of human enteropathogens remains to be determined. Presented here is the low-resolution (3.5 Å) structure of the CE8 from Yersinia enterocolitica (YeCE8). The high degree of structural conservation in the topology of the active-site cleft and catalytic apparatus that is shared with a characterized PME from a bacterial phytopathogen (i) indicates that YeCE8 is active on methylated pectin and (ii) highlights a more prominent role for pectin utilization in Yersinia than in other enteropathogenic species.
Fang, Evandro Fei; Wong, Jack Ho; Bah, Clara Shui Fern; Lin, Peng; Tsao, Sai Wah; Ng, Tzi Bun
2010-06-11
Here we report for the first time of a new Kunitz-type trypsin inhibitor (termed BvvTI) from seeds of the Camel's foot tree, Bauhinia variegata var. variegata. BvvTI shares the same reactive site residues (Arg, Ser) and exhibits a homology of N-terminal amino acid sequence to other Bauhinia protease inhibitors. The trypsin inhibitory activity (K(i), 0.1 x 10(-9)M) of BvvTI ranks the highest among them. Besides anti-HIV-1 reverse transcriptase activity, BvvTI could significantly inhibit the proliferation of nasopharyngeal cancer CNE-1 cells in a selective way. This may partially be contributed by its induction of cytokines and apoptotic bodies. These results unveil potential medicinal applications of BvvTI. (c) 2010 Elsevier Inc. All rights reserved.
2004-02-19
KENNEDY SPACE CENTER, FLA. - - U.S. Representative Ric Keller (left) listens intently to a presentation proposing the use of the Central Florida Research Park, near Orlando, as the site of NASA’s new Shared Services Center. NASA and Florida officials toured the research park as well. Central Florida leaders are proposing the research park as the site for the center, which would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
The cancellation of magnetic flux. II - In a decaying active region. [of sun
NASA Technical Reports Server (NTRS)
Martin, S. F.; Livi, S. H. B.; Wang, J.
1985-01-01
H-alpha filtergrams and videomagnetograms are used to study an active region during its period of decay on August 3-8, 1984; the decay had been initiated by a fragmentation process in which very small knots of magnetic flux separated from larger concentration of flux. The disappearance of magnetic flux was always observed when the small fragments of flux encountered other small fragments or concentrations of flux of opposite polarity. Such 'cancellations' are shared by both polarities of magnetic field, and it is deduced that the disappearance of flux occurred either at or within 5 arcsec of the apparent dividing line between the opposite polarities. All of the 22 flares observed during the decay of this region were initiated around sites where magnetic flux was cancelling or was deduced to be cancelling during the flares. It is hypothesized that cancellation was one of the necessary conditions for flaring in this active region.
Network of proteins, enzymes and genes linked to biomass degradation shared by Trichoderma species.
Horta, Maria Augusta Crivelente; Filho, Jaire Alves Ferreira; Murad, Natália Faraj; de Oliveira Santos, Eidy; Dos Santos, Clelton Aparecido; Mendes, Juliano Sales; Brandão, Marcelo Mendes; Azzoni, Sindelia Freitas; de Souza, Anete Pereira
2018-01-22
Understanding relationships between genes responsible for enzymatic hydrolysis of cellulose and synergistic reactions is fundamental for improving biomass biodegradation technologies. To reveal synergistic reactions, the transcriptome, exoproteome, and enzymatic activities of extracts from Trichoderma harzianum, Trichoderma reesei and Trichoderma atroviride under biodegradation conditions were examined. This work revealed co-regulatory networks across carbohydrate-active enzyme (CAZy) genes and secreted proteins in extracts. A set of 80 proteins and respective genes that might correspond to a common system for biodegradation from the studied species were evaluated to elucidate new co-regulated genes. Differences such as one unique base pair between fungal genomes might influence enzyme-substrate binding sites and alter fungal gene expression responses, explaining the enzymatic activities specific to each species observed in the corresponding extracts. These differences are also responsible for the different architectures observed in the co-expression networks.
NASA Technical Reports Server (NTRS)
2004-01-01
KENNEDY SPACE CENTER, FLA. KSC Director Jim Kennedy makes a presentation to NASA and other officials about the benefits of locating NASAs new Shared Services Center in the Central Florida Research Park, near Orlando. At the far left is Pamella J. Dana, Ph.D., director, Office of Tourism, Trade, and Economic Development in Florida. Central Florida leaders are proposing the research park as the site for the NASA Shared Services Center. The center would centralize NASAs payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
ERIC Educational Resources Information Center
Sinclair, Dorothy
This document examines the importance and difficulties in resource sharing and acquisition by libraries and introduces the procedures of the Site Appraisal for Area Resources Inventory (SAFARI) system as a method of comparative evaluation of subject collections among a group of libraries. Resource, or collection, sharing offers specific…
ERIC Educational Resources Information Center
Zimmerman, Melisa S.
2014-01-01
The growth of the Internet, and specifically social networking sites (SNSs) like Facebook, create opportunities for individuals to share private and identifiable information with a closed or open community. Internet crime has been on the rise and research has shown that criminals are using individuals' personal information pulled from social…
2004-02-19
KENNEDY SPACE CENTER, FLA. - NASA Administrator Sean O’Keefe (left) greets U.S. Representative Ric Keller during a tour of the Central Florida Research Park, near Orlando. Central Florida leaders are proposing the research park as the site for the new NASA Shared Services Center. The center would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
2004-02-19
KENNEDY SPACE CENTER, FLA. - NASA Administrator Sean O’Keefe (right) greets Florida Congressman Tom Feeney during a tour of the Central Florida Research Park, near Orlando. Central Florida leaders are proposing the research park as the site for the new NASA Shared Services Center. The center would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
McLuskey, Karen; Grewal, Jaspreet S.; Das, Debanu; ...
2016-03-03
Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other familiesmore » in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys 147, resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys 147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca 2+ for activity. Altogether, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms.« less
South Asia Water Resources Workshop: An effort to promote water quality data sharing in South Asia
DOE Office of Scientific and Technical Information (OSTI.GOV)
RAJEN,GAURAV; BIRINGER,KENT L.; BETSILL,J. DAVID
2000-04-01
To promote cooperation in South Asia on environmental research, an international working group comprised of participants from Bangladesh, India, Nepal, Pakistan, Sri Lanka, and the US convened at the Soaltee Hotel in Kathmandu, Nepal, September 12 to 14, 1999. The workshop was sponsored in part by the Cooperative Monitoring Center (CMC) at Sandia National Laboratories in Albuquerque, New Mexico, through funding provided by the Department of Energy (DOE) Office of Nonproliferation and National Security. The CMC promotes collaborations among scientists and researchers in regions throughout the world as a means of achieving common regional security objectives. In the long term,more » the workshop organizers and participants are interested in the significance of regional information sharing as a means to build confidence and reduce conflict. The intermediate interests of the group focus on activities that might eventually foster regional management of some aspects of water resources utilization. The immediate purpose of the workshop was to begin the implementation phase of a project to collect and share water quality information at a number of river and coastal estuary locations throughout the region. The workshop participants achieved four objectives: (1) gaining a better understanding of the partner organizations involved; (2) garnering the support of existing regional organizations promoting environmental cooperation in South Asia; (3) identifying sites within the region at which data is to be collected; and (4) instituting a data and information collection and sharing process.« less
Exploring how nurses and managers perceive shared governance.
Wilson, Janet; Speroni, Karen Gabel; Jones, Ruth Ann; Daniel, Marlon G
2014-07-01
Nurse managers have a pivotal role in the success of unit-based councils, which include direct care nurses. These councils establish shared governance to provide innovative, quality-based, and cost-effective nursing care. This study explored differences between direct care nurses' and nurse managers' perceptions of factors affecting direct care nurses' participation in unit-based and general shared governance activities and nurse engagement. In a survey research study, 425 direct care RNs and nurse managers were asked to complete a 26-item research survey addressing 16 shared governance factors; 144 participated (response rate = 33.8%). Most nurse participants provided direct care (N = 129, 89.6%; nurse managers = 15, 10.4%), were older than 35 (75.6%), had more than 5 years of experience (76.4%), and worked more than 35 hours per week (72.9%). Direct care nurses' and managers' perceptions showed a few significant differences. Factors ranked as very important by direct care nurses and managers included direct care nurses perceiving support from unit manager to participate in shared governance activities (84.0%); unit nurses working as a team (79.0%); direct care nurses participating in shared governance activities won't disrupt patient care (76.9%); and direct care nurses will be paid for participating beyond scheduled shifts (71.3%). Overall, 79.2% had some level of engagement in shared governance activities. Managers reported more engagement than direct care nurses. Nurse managers and unit-based councils should evaluate nurses' perceptions of manager support, teamwork, lack of disruption to patient care, and payment for participation in shared governance-related activities. These research findings can be used to evaluate hospital practices for direct care nurse participation in unit-based shared governance activities.
Giving Back: Collaborations with Others in Ecological Studies on the Nevada National Security Site
DOE Office of Scientific and Technical Information (OSTI.GOV)
Scott A. Wade; Kathryn S. Knapp; Cathy A. Wills
2013-02-24
Formerly named the Nevada Test Site, the Nevada National Security Site (NNSS) was the historical site for nuclear weapons testing from the 1950s to the early 1990s. The site was renamed in 2010 to reflect the diversity of nuclear, energy, and homeland security activities now conducted at the site. Biological and ecological programs and research have been conducted on the site for decades to address the impacts of radiation and to take advantage of the relatively undisturbed and isolated lands for gathering basic information on the occurrence and distribution of native plants and animals. Currently, the Office of the Assistantmore » Manager for Environmental Management of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) oversees the radiological biota monitoring and ecological compliance programs on the NNSS. The top priority of these programs are compliance with federal and state regulations. They focus on performing radiological dose assessments for the public who reside near the NNSS and for populations of plants and animals on the NNSS and in protecting important species and habitat from direct impacts of mission activities. The NNSS serves as an invaluable outdoor laboratory. The geographic and ecological diversity of the site offers researchers many opportunities to study human influences on ecosystems. NNSA/NSO has pursued collaborations with outside agencies and organizations to be able to conduct programs and studies that enhance radiological biota monitoring and ecosystem preservation when budgets are restrictive, as well as to provide valuable scientific information to the human health and natural resource communities at large. NNSA/NSO is using one current collaborative study to better assess the potential dose to the off-site public from the ingestion of game animals, the most realistic pathway for off-site public exposure at this time from radionuclide contamination on the NNSS. A second collaborative study is furthering desert tortoise conservation measures onsite. It is the goal of NNSA/NSO to continue to develop such collaborations in the sharing of resources, such as personnel, equipment, expertise, and NNSS land access, with outside entities to meet mutually beneficial goals cost effectively.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wade, Scott A.; Knapp, Kathryn S.; Wills, Cathy A.
2013-07-01
Formerly named the Nevada Test Site, the Nevada National Security Site (NNSS) was the historical site for nuclear weapons testing from the 1950's to the early 1990's. The site was renamed in 2010 to reflect the diversity of nuclear, energy, and homeland security activities now conducted at the site. Biological and ecological programs and research have been conducted on the site for decades to address the impacts of radiation and to take advantage of the relatively undisturbed and isolated lands for gathering basic information on the occurrence and distribution of native plants and animals. Currently, the Office of the Assistantmore » Manager for Environmental Management of the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office (NNSA/NSO) oversees the radiological biota monitoring and ecological compliance programs on the NNSS. The top priority of these programs are compliance with federal and state regulations. They focus on performing radiological dose assessments for the public who reside near the NNSS and for populations of plants and animals on the NNSS and in protecting important species and habitat from direct impacts of mission activities. The NNSS serves as an invaluable outdoor laboratory. The geographic and ecological diversity of the site offers researchers many opportunities to study human influences on ecosystems. NNSA/NSO has pursued collaborations with outside agencies and organizations to be able to conduct programs and studies that enhance radiological biota monitoring and ecosystem preservation when budgets are restrictive, as well as to provide valuable scientific information to the human health and natural resource communities at large. NNSA/NSO is using one current collaborative study to better assess the potential dose to the off-site public from the ingestion of game animals, the most realistic pathway for off-site public exposure at this time from radionuclide contamination on the NNSS. A second collaborative study is furthering desert tortoise conservation measures onsite. It is the goal of NNSA/NSO to continue to develop such collaborations in the sharing of resources, such as personnel, equipment, expertise, and NNSS land access, with outside entities to meet mutually beneficial goals cost effectively. (authors)« less
Shared use agreements and leisure time physical activity in North Carolina public schools.
Carlton, Troy A; Kanters, Michael A; Bocarro, Jason N; Floyd, Myron F; Edwards, Michael B; Suau, Luis J
2017-02-01
Although increasing community access to public schools through shared use agreements (SUAs) has been a recommended strategy for promoting physical activity (PA) among national, state and local organizations, empirical evidence examining the efficacy of SUAs is limited. This study examined the degree of usage and production of PA among schools with shared use, and how variation in PA output is related to characteristics of the school, type of activity, facility type, and when activity occurs. Data were collected in 20 schools across North Carolina using System for Observing Play and Recreation in Communities (SOPARC) and Structured Physical Activity Surveys (SPAS) to assess PA in school athletic facilities during out of school time. Findings indicated that although schools had a policy of shared or open use, most facilities were empty during non-school hours. Hierarchal linear regression models also showed that formal programming was positively associated with both use and PA levels. Given the abundance of empty facilities, community groups in need of space to facilitate structured PA programs should pursue avenues of sharing facilities with public schools. Furthermore, to increase the efficacy of shared use, structured physical activity programs may be needed. Future studies are encouraged to further explore the effects of the specific types of shared use programs on PA production as well other aspects of the built environment surrounding schools. Copyright © 2016 Elsevier Inc. All rights reserved.
Fostering interpersonal trust on social media: physicians' perspectives and experiences.
Panahi, Sirous; Watson, Jason; Partridge, Helen
2016-02-01
The problem of developing and sustaining mutual trust is one of the main barriers to knowledge sharing on social media platforms such as blogs, wikis, micro-blogs and social networking websites. While many studies argue that mutual trust is necessary for online communication and knowledge sharing, few have actually explored and demonstrated how physicians can establish and sustain trusted relationships on social media. To identify approaches through which physicians establish interpersonal trust on social media. Twenty-four physicians, who were active users of social media, were interviewed using a semi-structured approach between 2013 and 2014. Snowball sampling was employed for participant recruitment. The data were analysed using a thematic analysis approach. Physicians trust their peers on social media in a slightly different way than in face-to-face communication. The study found that the majority of participants established trust on social media mainly through previous personal interaction, authenticity and relevancy of voice, professional standing, consistency of communication, peer recommendation, and non-anonymous and moderated sites. Healthcare professionals need to approach social media carefully when using it for knowledge sharing, networking and developing trusted relations with like-minded peers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
A social media primer for professionals: digital dos and don'ts.
Bernhardt, Jay M; Alber, Julia; Gold, Robert S
2014-03-01
Social media sites have become powerful and important tools for health education, promotion, and communication activities as they have dramatically grown in popularity. Social media sites also offer many features that can be used for professional development and advancement. When used wisely and prudently, social media sites and platforms offer great potential for professional development by building and cultivating professional networks, as well as sharing information to increase one's recognition and improve one's reputation. They also provide a medium for increasing one's knowledge and awareness of timely news and trends by following important organizations, opinion leaders, and influential professionals. When used unwisely and imprudently, there is the potential to delay, damage, or even destroy one's professional and personal life. In this commentary, we offer recommendations for using Facebook, LinkedIn, and Twitter for professional development and caution against online behaviors that may have negative professional consequences. In summary, we believe that the strengths and benefits of social media for professional advancement and development far outweigh the risks and encourage health promotion professionals to properly engage these powerful tools.
Schools That Sustain: Lessening the Environmental Impact of New Construction.
ERIC Educational Resources Information Center
Peele, Katherine N.; Malone, Sara
2002-01-01
Discusses sustainable school design and its benefits to the environment, offering examples of illustrative schools. Provides suggestions on site selection (such as using smaller sites and recycling existing buildings), sharing facilities with the community, and construction elements that improve environmental impact (such as flexibility,…
The Employer's Voice: Frontline Workers and Workforce Development.
ERIC Educational Resources Information Center
Jobs for the Future, Boston, MA.
Seventeen small and mid-sized employers from Annie E. Casey Foundation Jobs Initiative sites addressed the challenges of recruiting, retaining, and promoting frontline workers. Employers shared collaboration experiences with Jobs Initiatives sites to develop effective, efficient strategies to prepare and support low-income residents. Firms relied…
Bilevel Shared Control Of A Remote Robotic Manipulator
NASA Technical Reports Server (NTRS)
Hayati, Samad A.; Venkataraman, Subramanian T.
1992-01-01
Proposed concept blends autonomous and teleoperator control modes, each overcoming deficiencies of the other. Both task-level and execution-level functions performed at local and remote sites. Applicable to systems with long communication delay between local and remote sites or systems intended to function partly autonomously.
Exploring the Impacts of Social Networking Sites on Academic Relations in the University
ERIC Educational Resources Information Center
Rambe, Patient
2011-01-01
Social networking sites (SNS) affordances for persistent interaction, collective generation of knowledge, and formation of peer-based clusters for knowledge sharing render them useful for developing constructivist knowledge environments. However, notwithstanding their academic value, these environments are not necessarily insulated from the…
A Solid Foundation: Key Capacities of Construction Pre-Apprenticeship Programs
ERIC Educational Resources Information Center
Helmer, Matt; Blair, Amy; Gerber, Allison
2012-01-01
This publication shares research from site visits conducted to construction pre-apprenticeship programs in Baltimore, Hartford, Milwaukee and Portland (OR). Findings from the site visits, which included interviews and focus groups with pre-apprenticeship program staff, public officials, philanthropic leaders, construction industry leaders and…
Systems of meaning and transference: Implicit significant-other activation evokes shared reality.
Przybylinski, Elizabeth; Andersen, Susan M
2015-10-01
Evidence shows that representations of significant others (SOs) are used in interpersonal relations-for example, in the social-cognitive process of transference (see Andersen & Chen, 2002), a process that is assumed to serve meaning-making functions (Glassman & Andersen, 1999b). Five studies tested the more specific notion that implicit activation of an SO representation in transference should indirectly activate the worldview shared with the SO, leading to its active pursuit, validation, and protection. Shared worldviews were assessed beforehand, both idiographically, as values (Studies 1 and 4), and nomothetically, as political ideology or religious beliefs (Studies 2, 3, and 5). In each experiment, participants learned about new persons, one subtly resembling their own SO. Transference was assessed (memory bias; positive evaluation; see Andersen, Reznik, & Manzella, 1996) and, crucially, as predicted, when considering the new person resembling their SO (vs. the control persons), participants showed faster response latencies in a lexical decision task to words reflecting the worldview shared with the SO (vs. held only personally, Studies 1-3, or only by the SO, Study 3). With this person, they also anticipated a more meaningful interaction and actively socially tuned to the SO-shared worldview, selecting conversation topics reflecting the SO-shared worldview (vs. personally held or SO-held topics, Studies 1-3). Finally, threatening the SO-shared worldview with this person (vs. threatening personally held, SO-held, or irrelevant worldviews) prompted goal activation to restore the disrupted meaning (Studies 4 and 5), assessed by response latency in a lexical decision task. Transference thus evokes shared meaning systems and serves epistemic functions. (c) 2015 APA, all rights reserved).
40 CFR 35.6235 - Cost sharing.
Code of Federal Regulations, 2011 CFR
2011-07-01
... ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Core Program... indirect costs of all activities covered by the Core Program Cooperative Agreement. Indian Tribes are not required to share in the cost of Core Program activities. The State must provide its cost share with non...
ERIC Educational Resources Information Center
Ementa, Christiana Ngozi; Ile, Chika Madu
2015-01-01
There are diverse social networking sites which range from those that provide social sharing and interaction to those that provide networks for professionals within same and other fields. Social networking sites require a user to sign up, create a profile and begin sending short messages about what the user is doing or thinking. The study sought…
Kuznetsova, Ekaterina; Nocek, Boguslaw; Brown, Greg; Makarova, Kira S; Flick, Robert; Wolf, Yuri I; Khusnutdinova, Anna; Evdokimova, Elena; Jin, Ke; Tan, Kemin; Hanson, Andrew D; Hasnain, Ghulam; Zallot, Rémi; de Crécy-Lagard, Valérie; Babu, Mohan; Savchenko, Alexei; Joachimiak, Andrzej; Edwards, Aled M; Koonin, Eugene V; Yakunin, Alexander F
2015-07-24
The haloacid dehalogenase (HAD)-like enzymes comprise a large superfamily of phosphohydrolases present in all organisms. The Saccharomyces cerevisiae genome encodes at least 19 soluble HADs, including 10 uncharacterized proteins. Here, we biochemically characterized 13 yeast phosphatases from the HAD superfamily, which includes both specific and promiscuous enzymes active against various phosphorylated metabolites and peptides with several HADs implicated in detoxification of phosphorylated compounds and pseudouridine. The crystal structures of four yeast HADs provided insight into their active sites, whereas the structure of the YKR070W dimer in complex with substrate revealed a composite substrate-binding site. Although the S. cerevisiae and Escherichia coli HADs share low sequence similarities, the comparison of their substrate profiles revealed seven phosphatases with common preferred substrates. The cluster of secondary substrates supporting significant activity of both S. cerevisiae and E. coli HADs includes 28 common metabolites that appear to represent the pool of potential activities for the evolution of novel HAD phosphatases. Evolution of novel substrate specificities of HAD phosphatases shows no strict correlation with sequence divergence. Thus, evolution of the HAD superfamily combines the conservation of the overall substrate pool and the substrate profiles of some enzymes with remarkable biochemical and structural flexibility of other superfamily members. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Motor output evoked by subsaccadic stimulation of primate frontal eye fields.
Corneil, Brian D; Elsley, James K; Nagy, Benjamin; Cushing, Sharon L
2010-03-30
In addition to its role in shifting the line of sight, the oculomotor system is also involved in the covert orienting of visuospatial attention. Causal evidence supporting this premotor theory of attention, or oculomotor readiness hypothesis, comes from the effect of subsaccadic threshold stimulation of the oculomotor system on behavior and neural activity in the absence of evoked saccades, which parallels the effects of covert attention. Here, by recording neck-muscle activity from monkeys and systematically titrating the level of stimulation current delivered to the frontal eye fields (FEF), we show that such subsaccadic stimulation is not divorced from immediate motor output but instead evokes neck-muscle responses at latencies that approach the minimal conduction time to the motor periphery. On average, neck-muscle thresholds were approximately 25% lower than saccade thresholds, and this difference is larger for FEF sites associated with progressively larger saccades. Importantly, we commonly observed lower neck-muscle thresholds even at sites evoking saccades
Modi, Tushar; Huihui, Jonathan; Ghosh, Kingshuk; Ozkan, S Banu
2018-06-19
Thioredoxins (THRXs)-small globular proteins that reduce other proteins-are ubiquitous in all forms of life, from Archaea to mammals. Although ancestral thioredoxins share sequential and structural similarity with the modern-day (extant) homologues, they exhibit significantly different functional activity and stability. We investigate this puzzle by comparative studies of their (ancient and modern-day THRXs') native state ensemble, as quantified by the dynamic flexibility index (DFI), a metric for the relative resilience of an amino acid to perturbations in the rest of the protein. Clustering proteins using DFI profiles strongly resemble an alternative classification scheme based on their activity and stability. The DFI profiles of the extant proteins are substantially different around the α3, α4 helices and catalytic regions. Likewise, allosteric coupling of the active site with the rest of the protein is different between ancient and extant THRXs, possibly explaining the decreased catalytic activity at low pH with evolution. At a global level, we note that the population of low-flexibility (called hinges) and high-flexibility sites increases with evolution. The heterogeneity (quantified by the variance) in DFI distribution increases with the decrease in the melting temperature typically associated with the evolution of ancient proteins to their modern-day counterparts.This article is part of a discussion meeting issue 'Allostery and molecular machines'. © 2018 The Author(s).
Characterization of network structure in stereoEEG data using consensus-based partial coherence.
Ter Wal, Marije; Cardellicchio, Pasquale; LoRusso, Giorgio; Pelliccia, Veronica; Avanzini, Pietro; Orban, Guy A; Tiesinga, Paul He
2018-06-06
Coherence is a widely used measure to determine the frequency-resolved functional connectivity between pairs of recording sites, but this measure is confounded by shared inputs to the pair. To remove shared inputs, the 'partial coherence' can be computed by conditioning the spectral matrices of the pair on all other recorded channels, which involves the calculation of a matrix (pseudo-) inverse. It has so far remained a challenge to use the time-resolved partial coherence to analyze intracranial recordings with a large number of recording sites. For instance, calculating the partial coherence using a pseudoinverse method produces a high number of false positives when it is applied to a large number of channels. To address this challenge, we developed a new method that randomly aggregated channels into a smaller number of effective channels on which the calculation of partial coherence was based. We obtained a 'consensus' partial coherence (cPCOH) by repeating this approach for several random aggregations of channels (permutations) and only accepting those activations in time and frequency with a high enough consensus. Using model data we show that the cPCOH method effectively filters out the effect of shared inputs and performs substantially better than the pseudo-inverse. We successfully applied the cPCOH procedure to human stereotactic EEG data and demonstrated three key advantages of this method relative to alternative procedures. First, it reduces the number of false positives relative to the pseudo-inverse method. Second, it allows for titration of the amount of false positives relative to the false negatives by adjusting the consensus threshold, thus allowing the data-analyst to prioritize one over the other to meet specific analysis demands. Third, it substantially reduced the number of identified interactions compared to coherence, providing a sparser network of connections from which clear spatial patterns emerged. These patterns can serve as a starting point of further analyses that provide insight into network dynamics during cognitive processes. These advantages likely generalize to other modalities in which shared inputs introduce confounds, such as electroencephalography (EEG) and magneto-encephalography (MEG). Copyright © 2018. Published by Elsevier Inc.
NASA Astrophysics Data System (ADS)
Grier, Jennifer A.; Buxner, Sanlyn; Schneider, Nick; Meinke, Bonnie; Shipp, Stephanie
2015-11-01
The NASA Education and Public Outreach (E/PO) Forums developed and provided resources for scientists through a five-year cooperative agreement. Through this work, the Fourms have supported scientists who are involved in E/PO and who wish to become involved. Forums have conducted interviews, facilitated education oral and poster sessions, provided ‘Help Desks’ for more information, curated activities, as well as produced guides, pamphlets, and tips sheets. Our interviews with over 30 planetary scientists allowed us to identify needs and target gaps in resources, ensuring we could provide scientists with effective support and products. Interviews were conducted in collaboration with the AAS Division of Planetary Sciences, with the goal of better understanding scientists’ requirements, barriers, attitudes, and perception of education and outreach work. We collected information about how scientists were engaged in E/PO activities (or not), what support they did or did not have, what resources they used in their efforts, and what resources they would like to have to support and improve their E/PO engagement. The Forums have convened and/or supported E/PO oral and poster sessions at a variety of annual meetings. These sessions allowed scientists to network, share lessons learned, and become aware of new resources and products. These meetings included the DPS, AAS, LPSC, AGU, ASP, IAU, and more. ‘Help Desks’ were offered to allow scientists the chance to have extended one-on-one conversations with E/PO providers in order to share their programs, and learn how to become involved. These have been particularly popular with early career scientists looking to extend their E/PO efforts. A host of education activities developed by the space science community have been archived at the NASA site “Wavelength” (nasawavelength.org). Special lists have been curated to allow scientists to easily target those activities that fit their particular needs, from engineering to higher education to outreach at public events. Guides, information sheets, and “How To’s” have been developed to answer specific questions and needs that scientists have specifically expressed. These resources are openly available at the NASA SMD community site (smdepo.org).
Landini, P; Volkert, M R
1995-04-07
The Escherichia coli aidB gene is part of the adaptive response to DNA methylation damage. Genes belonging to the adaptive response are positively regulated by the ada gene; the Ada protein acts as a transcriptional activator when methylated in one of its cysteine residues at position 69. Through DNaseI protection assays, we show that methylated Ada (meAda) is able to bind a DNA sequence between 40 and 60 base pairs upstream of the aidB transcriptional startpoint. Binding of meAda is necessary to activate transcription of the adaptive response genes; accordingly, in vitro transcription of aidB is dependent on the presence of meAda. Unmethylated Ada protein shows no protection against DNaseI digestion in the aidB promoter region nor does it promote aidB in vitro transcription. The aidB Ada-binding site shows only weak homology to the proposed consensus sequences for Ada-binding sites in E. coli (AAANNAA and AAAGCGCA) but shares a higher degree of similarity with the Ada-binding regions from other bacterial species, such as Salmonella typhimurium and Bacillus subtilis. Based on the comparison of five different Ada-dependent promoter regions, we suggest that a possible recognition sequence for meAda might be AATnnnnnnG-CAA. Higher concentrations of Ada are required for the binding of aidB than for the ada promoter, suggesting lower affinity of the protein for the aidB Ada-binding site. Common features in the Ada-binding regions of ada and aidB are a high A/T content, the presence of an inverted repeat structure, and their position relative to the transcriptional start site. We propose that these elements, in addition to the proposed recognition sequence, are important for binding of the Ada protein.
NASA Astrophysics Data System (ADS)
Morrill, P. L.; Rietze, A.; Kohl, L.; Miles, S.; Kavanagh, H.; Cox, A.; Brazelton, W. J.; Ishii, S.; Sherwood Lollar, B.; Schrenk, M. O.; Nealson, K. H.; Ziegler, S. E.; Ono, S.; Wang, D. T.; Lang, S. Q.; Cumming, E.
2014-12-01
Ultra-basic reducing springs at continental sites of serpentinization act as portals into the biogeochemistry of a subsurface ultramafic environment rich in hydrogen and methane gases. Field data and results from substrate addition microcosm experiments will be presented from two contrasting continental sites of serpentinization: the Tablelands, NL, CAN and The Cedars, CA, USA both Phanerozoic in age. These continental sites share geochemical characteristics that make these environments challenging for life, such as high pH, low Eh, scarce electron acceptors, and limited dissolved inorganic carbon for autotrophic growth. However, microbiological analyses have demonstrated that life does indeed exist in these environments. While environmental genomic studies indicated the potential metabolic capabilities of microorganisms in the sites, actual microbial metabolic activities in these environments remain unknown. To expand the understanding of biogeochemistry of the sites, we are conducting studies focusing on chemical and isotopic measurements, carbon substrate utilization, energy sources, and metabolic pathways of the microorganisms. Thus far, in situ geochemical data suggests that the methane from the Tablelands is primarily non-microbial, while the methane from The Cedars likely has some microbial contributions. To date, substrate addition microcosm experiments show no microbial production of methane from Tablelands' water and sediments. However, microbial carbon monoxide utilization has been observed in Tableland microcosms, but not in The Cedars microcosms. These results demonstrate how geochemistry and substrate addition experiments can be complementary for the determination of the processes favored at these continental sites of serpentinization.
NASA Shared Services Center breaks ground
2006-02-24
NASA officials and elected leaders were on hand for the groundbreaking ceremony of the NASA Shared Services Center Feb. 24, 2006, on the grounds of Stennis Space Center. The NSSC provides agency centralized administrative processing, human resources, procurement and financial services. From left, Louisiana Economic Development Secretary Mike Olivier, Stennis Space Center Director Rick Gilbrech, Computer Sciences Corp. President Michael Laphen, NASA Deputy Administrator Shana Dale, Rep. Gene Taylor, Sen. Trent Lott, Mississippi Gov. Haley Barbour, NASA Administrator Mike Griffin and Shared Services Center Executive Director Arbuthnot use golden shovels to break ground at the site.
NASA Shared Services Center breaks ground
NASA Technical Reports Server (NTRS)
2006-01-01
NASA officials and elected leaders were on hand for the groundbreaking ceremony of the NASA Shared Services Center Feb. 24, 2006, on the grounds of Stennis Space Center. The NSSC provides agency centralized administrative processing, human resources, procurement and financial services. From left, Louisiana Economic Development Secretary Mike Olivier, Stennis Space Center Director Rick Gilbrech, Computer Sciences Corp. President Michael Laphen, NASA Deputy Administrator Shana Dale, Rep. Gene Taylor, Sen. Trent Lott, Mississippi Gov. Haley Barbour, NASA Administrator Mike Griffin and Shared Services Center Executive Director Arbuthnot use golden shovels to break ground at the site.
Alves, Luiz C P S; Zappes, Camilah A; Oliveira, Rafael G; Andriolo, Artur; Azevedo, Alexandre de F
2013-01-01
Botos (Inia geoffrensis) are currently provisioned for use in tourist attractions in five sites in the Brazilian Amazon. Despite the known negative effects associated with human-wild dolphin interactions, this activity has been regulated and licensed in the Anavilhanas National Park in Novo Airão, Amazonas State, Brazil. We present an updated evaluation of the perception of the local community concerning the possible socioeconomic impacts of this tourism in Novo Airão. In April 2011, 45 interviews were conducted with inhabitants. A small segment of Novo Airão perceives currently itself as being economically dependent on the botos feeding tourism. Despite that, the economic benefits of this controversial activity apparently are not shared among most inhabitants, and botos feeding tourism is perceived as generating diverse negative effects. We conclude that if the activity was banned or modified into a less impacting tourist activity, this action would probably not majorly affect the lives of the general population.
An Early Assessment of Accountable Care Organizations Efforts to Engage Patients and Their Families
Shortell, Stephen M.; Sehgal, Neil; Bibi, Salma; Ramsay, Patricia P.; Neuhauser, Linda; Colla, Carrie H.; Lewis, Valerie A.
2017-01-01
Accountable Care Organizations (ACOs) have incentives to meet quality and expenditure targets and share in resulting savings. Achieving these goals will require ACOs to engage more actively with patients and their families. The extent to which ACOs do so is currently unknown. Using mixed-methods including a national survey, phone interviews and site-visits; we examine the extent to which ACOs actively engage patients and their families, explore challenges involved; and consider approaches for dealing with those challenges. Results indicate that greater ACO use of patient activation and engagement (PAE) activities at the point-of-care may influence more positive leadership perceptions of the impact of PAE investments on ACO costs, quality, and outcomes of care. We identify a number of important practices associated with greater PAE, including high-level leadership commitment, goal-setting supported by adequate resources, extensive provider training and use of inter-disciplinary care teams, and frequent monitoring and reporting on progress. PMID:26038349
Federal Register 2010, 2011, 2012, 2013, 2014
2013-01-16
... address. FOR FURTHER INFORMATION CONTACT: Arlene Bajusz, Office of Policy, Regulations, and Analysis at... meeting of DOI/BOEM information needs on subsistence food harvest and sharing activities in various... gas development on subsistence food harvest and sharing activities. It investigates the resilience of...
ERIC Educational Resources Information Center
Loftus, Maria; Tiernan, Peter; Cherian, Sebastian
2014-01-01
Evidence has shown that students have greatly increased their consumption of digital video, principally through video sharing sites. In parallel, students' participation in video sharing and creation has also risen. As educators, we need to question how this can be effectively translated into a positive learning experience for students, whilst…
The Demands of Decentralization: Skills and Knowledge for Leaders in Restructured Schools
ERIC Educational Resources Information Center
Gok, Kubilay; Peterson, Kent D.; Warren, Valli D.
2005-01-01
One of the most visible and widespread of the current educational reforms is the attempt to decentralize authority to schools and to involve teachers and others in shared decision making. Often occurring together as site-based shared decision making (SBDM), this reform is turning out to be more difficult to implement than once thought. Few noted…
Utah CTE: Running in New Circles
ERIC Educational Resources Information Center
Dobson, Kristine; Fischio, Shannon; Thomas, Susan
2011-01-01
Although the authors admit that they do not have any fool-proof formulas to offer for using Web site, blog, Facebook, Twitter, or YouTube in order to more successfully share one's career and technical education (CTE) story, they share a story of their own journey and hope that it may help people to run faster and more effectively in these new…
Swalm, Brooke M; Hallenbeck, Kenneth K; Majer, Christina R; Jin, Lei; Scott, Margaret Porter; Moyer, Mikel P; Copeland, Robert A; Wigle, Tim J
2013-07-15
H3K27 (histone H3 Lys27) methylation is an important epigenetic modification that regulates gene transcription. In humans, EZH (enhancer of zeste homologue) 1 and EZH2 are the only enzymes capable of catalysing methylation of H3K27. There is great interest in understanding structure-function relationships for EZH2, as genetic alterations in this enzyme are thought to play a causal role in a number of human cancers. EZH2 is challenging to study because it is only active in the context of the multi-subunit PRC2 (polycomb repressive complex 2). vSET is a viral lysine methyltransferase that represents the smallest protein unit capable of catalysing H3K27 methylation. The crystal structure of this minimal catalytic protein has been solved and researchers have suggested that vSET might prove useful as an EZH2 surrogate for the development of active site-directed inhibitors. To test this proposition, we conducted comparative enzymatic analysis of human EZH2 and vSET and report that, although both enzymes share similar preferences for methylation of H3K27, they diverge in terms of their permissiveness for catalysing methylation of alternative histone lysine sites, their relative preferences for utilization of multimeric macromolecular substrates, their active site primary sequences and, most importantly, their sensitivity to inhibition by drug-like small molecules. The cumulative data led us to suggest that EZH2 and vSET have very distinct active site structures, despite the commonality of the reaction catalysed by the two enzymes. Hence, the EZH2 and vSET pair of enzymes represent an example of convergent evolution in which distinct structural solutions have developed to solve a common catalytic need.
Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases
Li, Yun R; Li, Jin; Zhao, Sihai D; Bradfield, Jonathan P; Mentch, Frank D; Maggadottir, S Melkorka; Hou, Cuiping; Abrams, Debra J; Chang, Diana; Gao, Feng; Guo, Yiran; Wei, Zhi; Connolly, John J; Cardinale, Christopher J; Bakay, Marina; Glessner, Joseph T; Li, Dong; Kao, Charlly; Thomas, Kelly A; Qiu, Haijun; Chiavacci, Rosetta M; Kim, Cecilia E; Wang, Fengxiang; Snyder, James; Richie, Marylyn D; Flatø, Berit; Førre, Øystein; Denson, Lee A; Thompson, Susan D; Becker, Mara L; Guthery, Stephen L; Latiano, Anna; Perez, Elena; Resnick, Elena; Russell, Richard K; Wilson, David C; Silverberg, Mark S; Annese, Vito; Lie, Benedicte A; Punaro, Marilynn; Dubinsky, Marla C; Monos, Dimitri S; Strisciuglio, Caterina; Staiano, Annamaria; Miele, Erasmo; Kugathasan, Subra; Ellis, Justine A; Munro, Jane E; Sullivan, Kathleen E; Wise, Carol A; Chapel, Helen; Cunningham-Rundles, Charlotte; Grant, Struan F A; Orange, Jordan S; Sleiman, Patrick M A; Behrens, Edward M; Griffiths, Anne M; Satsangi, Jack; Finkel, Terri H; Keinan, Alon; Prak, Eline T Luning; Polychronakos, Constantin; Baldassano, Robert N; Li, Hongzhe; Keating, Brendan J; Hakonarson, Hakon
2016-01-01
Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ2 meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico–replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases. PMID:26301688
Social Bookmarking in Academic Libraries: Trends and Applications
ERIC Educational Resources Information Center
Redden, Carla S.
2010-01-01
This paper presents an exploration of the potential utilization of social bookmarking web sites by academic libraries. These web sites, which allow users and organizations to create accounts for bookmarking online content, provide academic libraries tools to collaborate and network, organize and share electronic resources and teach information…
Search the Division of Finance site DOF State of Alaska Finance Home Content Area Accounting Charge Cards IRIS HRM Login LearnAlaska SFOA SharePoint Site Vendor Self Service (VSS) Content Area Accounting Dunayski, Accounting Services Lead Danielle Meier, State E-Travel Manager Stephanie Church, IRIS Financial
YouTube as a Participatory Culture
ERIC Educational Resources Information Center
Chau, Clement
2010-01-01
There is an explosion of youth subscriptions to original content-media-sharing Web sites such as YouTube. These Web sites combine media production and distribution with social networking features, making them an ideal place to create, connect, collaborate, and circulate. By encouraging youth to become media creators and social networkers, new…
Online Communication and Adolescent Relationships
ERIC Educational Resources Information Center
Subrahmanyam, Kaveri; Greenfield, Patricia
2008-01-01
Over the past decade, technology has become increasingly important in the lives of adolescents. As a group, adolescents are heavy users of newer electronic communication forms such as instant messaging, e-mail, and text messaging, as well as communication-oriented Internet sites such as blogs, social networking, and sites for sharing photos and…
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O'Donnell, Clifford R; Tharp, Roland G
2012-03-01
Cultural and community psychology share a common emphasis on context, yet their leading journals rarely cite each other's articles. Greater integration of the concepts of culture and community within and across their disciplines would enrich and facilitate the viability of cultural community psychology. The contextual theory of activity settings is proposed as one means to integrate the concepts of culture and community in cultural community psychology. Through shared activities, participants develop common experiences that affect their psychological being, including their cognitions, emotions, and behavioral development. The psychological result of these experiences is intersubjectivity. Culture is defined as the shared meanings that people develop through their common historic, linguistic, social, economic, and political experiences. The shared meanings of culture arise through the intersubjectivity developed in activity settings. Cultural community psychology presents formidable epistemological challenges, but overcoming these challenges could contribute to the transformation and advancement of community psychology.
Bagayoko, Cheick Oumar; Traoré, Diakaridia; Thevoz, Laurence; Diabaté, Soumahila; Pecoul, David; Niang, Mahamoudane; Bediang, Georges; Traoré, Seydou Tidiane; Anne, Abdrahamane; Geissbuhler, Antoine
2014-01-01
The aim of this study was to evaluate the impact of telehealth on 1) the diagnosis, and management in obstetrics and cardiology, 2) health care costs from patients' perspectives, 3) attendance at health centres located in remote areas of Mali. The impact of telehealth on health care utilization, quality, and costs was assessed using a five-point Likert-scale based questionnaire consisting of three dimensions. It was completed by health care professionals in four district hospitals. The role of telehealth on attendance at health centres was also assessed based on data collected from the consultations logs before and during the project, between project sites and control sites. Referrals specific to the activities of the research study were also evaluated using a questionnaire to measure the real share of telehealth tools in increasing attendance at project sites. Finally, the cost savings achieved was estimated using the transport and lodging costs incurred if patients were to travel to the capital city for the same tests or care. The telehealth activities contributed to improving medical diagnoses in cardiology and obstetrics (92.6%) and the patients' management system on site (96.2%). The attendance records at health centres increased from 8 to 35% at all project sites during the study period. Patients from project sites saved an average of 12380 XOF (CFA Francs) or 25 USD (American dollar) and a maximum of 35000 XOF or 70 USD compared to patients from neighbouring sites, who must go to the capital city to receive the same care. We conclude that in Mali, enhanced training in ultrasound / electrocardiography and the introduction of telehealth have improved the health system in remote areas and resulted in high levels of appropriate diagnosis and patient management in the areas of obstetrics and cardiology. Telehealth can also significantly reduce the cost to the patient.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
2013-12-01
The National Renewable Energy Laboratory (NREL) has developed OpenEI.org, a public, open, data-sharing platform where consumers, analysts, industry experts, and energy decision makers can go to boost their energy IQs, search for energy data, share data, and get access to energy applications. The free site blends elements of social media, linked open-data practices, and MediaWiki-based technology to build a collaborative environment for creating and sharing energy data with the world. The result is a powerful platform that is helping government and industry leaders around the world define policy options, make informed investment decisions, and create new businesses.
Croager, Emma J.; Gout, Alexander M.; Abraham, Lawrence J.
2000-01-01
CD30, as a member of the tumor necrosis factor (TNF) receptor family, is expressed on the surface of activated lymphoid cells. CD30 overexpression is a characteristic of lymphoproliferative diseases such as Hodgkin’s/non-Hodgkin’s lymphomas, embryonal carcinoma, and a number of Th2-associated diseases. The CD30 gene has been mapped to a region of the murine genome that is involved in susceptibility to systemic lupus erythematosus. Functionally, CD30 may play a role in the deletion of autoreactive T cells. We were interested in determining the molecular nature of CD30 overexpression. Sequence comparison has revealed significant identity between the TATA-less human and murine CD30 promoters; they share a number of common consensus binding motifs. Transfection assays identified three regions of transcriptional importance; the region between position −1.2 kb and −336 bp, containing a CCAT microsatellite sequence, a conserved Sp1 site at positions −43 to −38, and a downstream promoter element (DPE) at positions +24 to +29. EMSA and DNase I footprinting showed specific DNA-protein interactions of the CD30 promoter with the Sp1 site and the CCAT repeat region. The DPE element was shown to be essential for start site selection. We conclude that the conserved Sp1 site at −43 to −38 is associated with maximum reporter gene activity, the DPE element is required for start site selection, and the CCAT tetranucleotide repeats act to repress transcription. We also have shown that the microsatellite is multiallelic, when we screened a random healthy population. Further studies are required to determine whether microsatellite instability in the repressor predisposes susceptible individuals to CD30 overexpression. PMID:10793083
DeRita, Leo; Dai, Sheng; Lopez-Zepeda, Kimberly; Pham, Nicholas; Graham, George W; Pan, Xiaoqing; Christopher, Phillip
2017-10-11
Oxide-supported precious metal nanoparticles are widely used industrial catalysts. Due to expense and rarity, developing synthetic protocols that reduce precious metal nanoparticle size and stabilize dispersed species is essential. Supported atomically dispersed, single precious metal atoms represent the most efficient metal utilization geometry, although debate regarding the catalytic activity of supported single precious atom species has arisen from difficulty in synthesizing homogeneous and stable single atom dispersions, and a lack of site-specific characterization approaches. We propose a catalyst architecture and characterization approach to overcome these limitations, by depositing ∼1 precious metal atom per support particle and characterizing structures by correlating scanning transmission electron microscopy imaging and CO probe molecule infrared spectroscopy. This is demonstrated for Pt supported on anatase TiO 2 . In these structures, isolated Pt atoms, Pt iso , remain stable through various conditions, and spectroscopic evidence suggests Pt iso species exist in homogeneous local environments. Comparing Pt iso to ∼1 nm preoxidized (Pt ox ) and prereduced (Pt metal ) Pt clusters on TiO 2 , we identify unique spectroscopic signatures of CO bound to each site and find CO adsorption energy is ordered: Pt iso ≪ Pt metal < Pt ox . Pt iso species exhibited a 2-fold greater turnover frequency for CO oxidation than 1 nm Pt metal clusters but share an identical reaction mechanism. We propose the active catalytic sites are cationic interfacial Pt atoms bonded to TiO 2 and that Pt iso exhibits optimal reactivity because every atom is exposed for catalysis and forms an interfacial site with TiO 2 . This approach should be generally useful for studying the behavior of supported precious metal atoms.
USArray Siting Outreach: Telling the EarthScope Story
NASA Astrophysics Data System (ADS)
Dorr, P. M.; Taber, J. J.; McQuillan, P.; Busby, R. W.; Woodward, R.
2013-12-01
USArray has engaged in a variety of activities that involve students in and inform the general public about EarthScope. Examples include the highly successful Transportable Array Student Siting Program that employed students and faculty from colleges and universities in the identification of sites for future Transportable Array stations in their region, and a range of informal education and media opportunities where information about EarthScope and its discoveries are shared with educators and the public. During the course of eight summers, more than 135 students from about 55 institutions conducted site reconnaissance for nearly 1375 sites from the West Coast to the East Coast, and from the Gulf of Mexico to the Great Lakes and southern Canada. While telling the EarthScope story, students who participated in the program increased their professional skills and deepened their personal growth. Other students had opportunities to engage in EarthScope-related research as part of the Research Experiences for Undergraduates program. Several EarthScope-focused outreach products for the public and educational audiences have been developed including Ground Motion Visualizations, EarthScope-centric and regional content sets for the IRIS Active Earth Monitor (AEM), and animations of earth processes. A kiosk loan program has helped to broadly disseminate the AEM displays. There have also been articles published in university, local and regional newspapers; stories appearing in national and international print and broadcast media; and documentaries produced by some of the world's most respected scientific and educational production companies that have included a segment about EarthScope and the Transportable Array. Over the next five years, USArray will be deploying and operating Transportable Array stations in Alaska and western Canada. This challenging environment will offer new opportunities to connect with communities throughout the region including native populations.
PPARγ and NF-κB regulate the gene promoter activity of their shared repressor, TNIP1
Gurevich, Igor; Zhang, Carmen; Encarnacao, Priscilla C.; Struzynski, Charles P.; Livings, Sarah E.; Aneskievich, Brian J.
2011-01-01
Human TNFAIP3 interacting protein 1 (TNIP1) has diverse functions including support of HIV replication through its interaction with viral Nef and matrix proteins, reduction of TNFα-induced signaling through its interaction with NF-κB pathway proteins, and corepression of agonist-bound retinoic acid receptors and peroxisome proliferator-activated receptors (PPAR). The wide tissue distribution of TNIP1 provides the opportunity to influence numerous cellular responses in these roles and defining control of TNIP1 expression would be central to improved understanding of its impact on cell function. We cloned 6kb of the human TNIP1 promoter and performed predictive and functional analyses to identify regulatory elements. The promoter region proximal to the transcription start site is GC-rich without a recognizable TATA box. In contrast to this proximal ~500bp region, 6kb of the promoter increased reporter construct constitutive activity over five-fold. Throughout the 6kb length, in silico analysis identified several potential binding sites for both constitutive and inducible transcription factors; among the latter were candidate NF-κB binding sequences and peroxisome proliferator response elements (PPREs). We tested NF-κB and PPAR regulation of the endogenous TNIP1 gene and cloned promoter by expression studies, electrophoretic mobility shift assays, and chromatin immunoprecipitations. We validated NF-κB sites in the TNIP1 promoter proximal and distal regions as well as one PPRE in the distal region. The ultimate control of the TNIP1 promoter is likely to be a combination of constitutive transcription factors and those subject to activation such as NF-κB and PPAR. PMID:22001530
Kuhn, Isabelle; Kellenberger, Esther; Rognan, Didier; Lund, Frances E.; Muller-Steffner, Hélène; Schuber, Francis
2008-01-01
Schistosoma mansoni NAD(P)+ catabolizing enzyme (SmNACE) is a new member of the ADP-ribosyl cyclase family. In contrast to all the other enzymes which are involved in the production of metabolites that elicit Ca2+ mobilization, SmNACE is virtually unable to transform NAD+ into the second messenger cyclic ADP-ribose (cADPR). Sequence alignments revealed that one of four conserved residues within the active site of these enzymes was replaced in SmNACE by a histidine (His103) instead of the highly conserved tryptophan. To find out whether the inability of SmNACE to catalyze the canonical ADP-ribosyl cyclase reaction is linked to this change we have replaced His103 with a tryptophan. The H103W mutation in SmNACE was indeed found to restore ADP-ribosyl cyclase activity as cADPR amounts for 7% of the reaction products, i.e., a value larger than observed for other members of this family such as CD38. Introduction of a Trp103 residue provides some of the binding characteristics of mammalian ADP-ribosyl cyclases such as increased affinity for Cibacron blue and slow-binding inhibition by araF-NAD+. Homology modeling of wild-type and H103W mutant three-dimensional structures, and docking of substrates within the active sites, provide new insight into the catalytic mechanism of SmNACE. Both residue side chains share similar roles in the nicotinamide-ribose bond cleavage step leading to an E.ADP-ribosyl reaction intermediate. They diverge however in the evolution of this intermediate; His103 provides a more polar environment favoring the accessibility to water and hydrolysis leading to ADP-ribose at the expense of the intramolecular cyclization pathway resulting in cADPR. PMID:17002287
The Non-Problem of the Other Minds: A Neurodevelopmental Perspective on Shared Intentionality
ERIC Educational Resources Information Center
Colle, Livia; Becchio, Cristina; Bara, Bruno G.
2008-01-01
In this paper, we combine neurological and developmental evidences in order to differentiate between two levels of sharing: dyadic sharing, virtually present from birth and depending on the activation of shared representation, and triadic sharing, requiring that agents not only share a common representation, but also represent complementary…
NASA Technical Reports Server (NTRS)
2004-01-01
KENNEDY SPACE CENTER, FLA. After a presentation about the assets of the Central Florida Research Park, near Orlando, as the site of NASAs new Shared Services Center, Congressmen Tom Feeney (center) and Dave Weldon (right) share a humorous moment with NASA Administrator Sean OKeefe (foreground). Six sites around the U.S. are under consideration for location of the Center, which would centralize NASAs payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Others attending the presentation included Congressman Dave Weldon, U.S. Representative Ric Keller, Center Director Jim Kennedy and Pamella J. Dana, Ph.D., director, Office of Tourism, Trade, and Economic Development in Florida.
Knowledge diffusion within a large conservation organization and beyond.
Fisher, Jonathan R B; Montambault, Jensen; Burford, Kyle P; Gopalakrishna, Trisha; Masuda, Yuta J; Reddy, Sheila M W; Torphy, Kaitlin; Salcedo, Andrea I
2018-01-01
The spread and uptake of new ideas (diffusion of innovations) is critical for organizations to adapt over time, but there is little evidence of how this happens within organizations and to their broader community. To address this, we analyzed how individuals accessed information about a recent science innovation at a large, international, biodiversity conservation non-profit-The Nature Conservancy-and then traced the flow of how this information was shared within the organization and externally, drawing on an exceptionally data-rich environment. We used surveys and tracking of individual internet activity to understand mechanisms for early-stage diffusion (knowledge seeking and sharing) following the integration of social science and evidence principles into the institutional planning framework: Conservation by Design (CbD 2.0). Communications sent to all employees effectively catalyzed 56.4% to exhibit knowledge seeking behavior, measured by individual downloads from and visits to a restricted-access site. Individuals who self-reported through a survey that they shared information about CbD 2.0 internally were more likely to have both received and sought out information about the framework. Such individuals tended to hold positions within a higher job grade, were more likely to train others on CbD as part of their job, and to enroll in other online professional development offerings. Communication strategies targeting external audiences did not appear to influence information seeking behavior. Staff who engaged in internal knowledge sharing and adopting "evidence" practices from CbD 2.0 were more likely to have shared the document externally. We found a negative correlation with external sharing behavior and in-person trainings. Our findings suggest repeated, direct email communications aimed at wide audiences can effectively promote diffusion of new ideas. We also found a wide range of employee characteristics and circumstances to be associated with knowledge diffusion behavior (at both an organizational and individual level).
Knowledge diffusion within a large conservation organization and beyond
Montambault, Jensen; Burford, Kyle P.; Gopalakrishna, Trisha; Masuda, Yuta J.; Reddy, Sheila M. W.; Torphy, Kaitlin; Salcedo, Andrea I.
2018-01-01
The spread and uptake of new ideas (diffusion of innovations) is critical for organizations to adapt over time, but there is little evidence of how this happens within organizations and to their broader community. To address this, we analyzed how individuals accessed information about a recent science innovation at a large, international, biodiversity conservation non-profit–The Nature Conservancy–and then traced the flow of how this information was shared within the organization and externally, drawing on an exceptionally data-rich environment. We used surveys and tracking of individual internet activity to understand mechanisms for early-stage diffusion (knowledge seeking and sharing) following the integration of social science and evidence principles into the institutional planning framework: Conservation by Design (CbD 2.0). Communications sent to all employees effectively catalyzed 56.4% to exhibit knowledge seeking behavior, measured by individual downloads from and visits to a restricted-access site. Individuals who self-reported through a survey that they shared information about CbD 2.0 internally were more likely to have both received and sought out information about the framework. Such individuals tended to hold positions within a higher job grade, were more likely to train others on CbD as part of their job, and to enroll in other online professional development offerings. Communication strategies targeting external audiences did not appear to influence information seeking behavior. Staff who engaged in internal knowledge sharing and adopting “evidence” practices from CbD 2.0 were more likely to have shared the document externally. We found a negative correlation with external sharing behavior and in-person trainings. Our findings suggest repeated, direct email communications aimed at wide audiences can effectively promote diffusion of new ideas. We also found a wide range of employee characteristics and circumstances to be associated with knowledge diffusion behavior (at both an organizational and individual level). PMID:29494644
A vision for end-to-end data services to foster international partnerships through data sharing
NASA Astrophysics Data System (ADS)
Ramamurthy, M.; Yoksas, T.
2009-04-01
Increasingly, the conduct of science requires scientific partnerships and sharing of knowledge, information, and other assets. This is particularly true in our field where the highly-coupled Earth system and its many linkages have heightened the importance of collaborations across geographic, disciplinary, and organizational boundaries. The climate system, for example, is far too complex a puzzle to be unraveled by individual investigators or nations. As articulated in the NSF Strategic Plan: FY 2006-2011, "…discovery increasingly requires expertise of individuals from different disciplines, with diverse perspectives, and often from different nations, working together to accommodate the extraordinary complexity of today's science and engineering challenges." The Nobel Prize winning IPCC assessments are a prime example of such an effort. Earth science education is also uniquely suited to drawing connections between the dynamic Earth system and societal issues. Events like the 2004 Indian Ocean tsunami and Hurricane Katrina provide ample evidence of this relevance, as they underscore the importance of timely and interdisciplinary integration and synthesis of data. Our success in addressing such complex problems and advancing geosciences depends on the availability of a state-of-the-art and robust cyberinfrastructure, transparent and timely access to high-quality data from diverse sources, and requisite tools to integrate and use the data effectively, toward creating new knowledge. To that end, Unidata's vision calls for providing comprehensive, well-integrated, and end-to-end data services for the geosciences. These include an array of functions for collecting, finding, and accessing data; data management tools for generating, cataloging, and exchanging metadata; and submitting or publishing, sharing, analyzing, visualizing, and integrating data. When this vision is realized, users — no matter where they are, how they are connected to the Internet, or what computing device they use — will be able to find and access a plethora of geosciences data, experience how all of the aforementioned services work together, and use our tools and services both productively and creatively in their research, education, and other activities. Permit me to elucidate on what that vision really means for you by drawing a simple analogy. Most of you are familiar with Amazon and eBay e-commerce sites and content sharing sites like You Tube and Flickr. On the eBay marketplace, people can sell practically anything at any time and buyers can share their experience of purchasing a product or the reputation of a seller. Likewise, at Amazon, thousands of merchants sell their goods and millions of customers not only buy those goods, but provide a review or opinion of the products they buy and share their experiences with the purchase. Similarly, You Tube and Flickr are sites tailored to video- and photo-sharing, respectively, where users can upload their own content and share them with millions of other users, including family and friends. What all these sites have enabled is a sense of a virtual community in which users can search and browse products or content, comment and rate those products from anywhere, at any time, and via any Internet-enabled device like an iPhone, laptop, or a desktop computer. In essence, these enterprises have fundamentally altered people's buying modes and behavior toward purchases. I believe that similar approaches, appropriately tailored to meet the needs of the scientific community, can be adopted to provide and share geosciences data in the future. For example, future case-study data access systems, in addition to providing datasets and tools, will provide services that allow users to provide commentaries of a weather event, say a hurricane, as well as provide feedback on the quality, usefulness and interpretation of the datasets through integrated blogs, forums and Wikis, upload and share products they derive, ancillary materials that users might have gathered (such as photos and videos from the storm), and publications and curricular materials they develop, all through a single data portal. In essence, such case study collections will be "living" or dynamic, allowing users to be also contributors as they add value to and grow existing case study collections. At Unidata, our goal is to provide a portfolio of integrated data services toward realizing the vision presented here so that the geosciences community can continue to address societally relevant problems such as weather prediction, atmospheric and oceanic variability, climate change, and the water cycle, and advance scientific discovery.
Lintott, Paul R; Davison, Sophie; van Breda, John; Kubasiewicz, Laura; Dowse, David; Daisley, Jonathan; Haddy, Emily; Mathews, Fiona
2018-01-01
Acoustic surveys of bats are one of the techniques most commonly used by ecological practitioners. The results are used in Ecological Impact Assessments to assess the likely impacts of future developments on species that are widely protected in law, and to monitor developments' postconstruction. However, there is no standardized methodology for analyzing or interpreting these data, which can make the assessment of the ecological value of a site very subjective. Comparisons of sites and projects are therefore difficult for ecologists and decision-makers, for example, when trying to identify the best location for a new road based on relative bat activity levels along alternative routes. Here, we present a new web-based, data-driven tool, Ecobat, which addresses the need for a more robust way of interpreting ecological data. Ecobat offers users an easy, standardized, and objective method for analyzing bat activity data. It allows ecological practitioners to compare bat activity data at regional and national scales and to generate a numerical indicator of the relative importance of a night's worth of bat activity. The tool is free and open-source; because the underlying algorithms are already developed, it could easily be expanded to new geographical regions and species. Data donation is required to ensure the robustness of the analyses; we use a positive feedback mechanism to encourage ecological practitioners to share data by providing in return high quality, contextualized data analysis, and graphical visualizations for direct use in ecological reports.
Shen, Chen; Chu, Joanna TW; Wan, Alice; Viswanath, Kasisomayajula; Chan, Sophia Siu Chee; Lam, Tai Hing
2017-01-01
Background The use of information and communication technologies (ICTs) for information sharing among family members is increasing dramatically. However, little is known about the associated factors and the influence on family well-being. Objective The authors investigated the pattern and social determinants of family life information sharing with family and the associations of different methods of sharing with perceived family health, happiness, and harmony (3Hs) in Hong Kong, where mobile phone ownership and Internet access are among the most prevalent, easiest, and fastest in the world. Methods A territory-wide population-based telephone survey was conducted from January to August 2016 on different methods of family life information (ie, information related to family communication, relationships with family members, emotion and stress management) sharing with family members, including face-to-face, phone, instant messaging (IM), social media sites, video calls, and email. Family well-being was assessed by three single items on perceived family health, happiness, and harmony, with higher scores indicating better family well-being. Adjusted prevalence ratios were used to assess the associations of sociodemographic factors with family life information sharing, and adjusted beta coefficients for family well-being. Results Of 2017 respondents, face-to-face was the most common method to share family life information (74.45%, 1502/2017), followed by IM (40.86%, 824/2017), phone (28.10%, 567/2017), social media sites (11.91%, 240/2017), video calls (5.89%, 119/2017), and email (5.48%, 111/2017). Younger age and higher education were associated with the use of any (at least one) method, face-to-face, IM, and social media sites for sharing family life information (all P for trend <.01). Higher education was most strongly associated with the use of video calls (adjusted prevalence ratio=5.61, 95% CI 2.29-13.74). Higher household income was significantly associated with the use of any method, face-to-face, and IM (all P for trend <.05). Sharing family life information was associated with a higher level of perceived family well-being (beta=0.56, 95% CI 0.37-0.75), especially by face-to-face (beta=0.62, 95% CI 0.45-0.80) and video calls (beta=0.34, 95% CI 0.04-0.65). The combination of face-to-face and video calls was most strongly associated with a higher level of perceived family well-being (beta=0.81, 95% CI 0.45-1.16). Conclusions The differential use of ICTs to share family life information was observed. The prevalence of video calls was low, but associated with much better family well-being. The results need to be confirmed by prospective and intervention studies to promote the use of video calls to communicate and share information with family, particularly in disadvantaged groups. PMID:29170145
Managing virtual machines with Vac and Vcycle
NASA Astrophysics Data System (ADS)
McNab, A.; Love, P.; MacMahon, E.
2015-12-01
We compare the Vac and Vcycle virtual machine lifecycle managers and our experiences in providing production job execution services for ATLAS, CMS, LHCb, and the GridPP VO at sites in the UK, France and at CERN. In both the Vac and Vcycle systems, the virtual machines are created outside of the experiment's job submission and pilot framework. In the case of Vac, a daemon runs on each physical host which manages a pool of virtual machines on that host, and a peer-to-peer UDP protocol is used to achieve the desired target shares between experiments across the site. In the case of Vcycle, a daemon manages a pool of virtual machines on an Infrastructure-as-a-Service cloud system such as OpenStack, and has within itself enough information to create the types of virtual machines to achieve the desired target shares. Both systems allow unused shares for one experiment to temporarily taken up by other experiements with work to be done. The virtual machine lifecycle is managed with a minimum of information, gathered from the virtual machine creation mechanism (such as libvirt or OpenStack) and using the proposed Machine/Job Features API from WLCG. We demonstrate that the same virtual machine designs can be used to run production jobs on Vac and Vcycle/OpenStack sites for ATLAS, CMS, LHCb, and GridPP, and that these technologies allow sites to be operated in a reliable and robust way.
Idea Swap: The Best Ideas Come from Teachers Like You!
ERIC Educational Resources Information Center
Instructor, 2006
2006-01-01
This article presents several activities and teaching ideas shared by teachers. One teacher shared how an Egyptian mummy-making activity can be a great hands-on learning through time. Another teacher shared how a bowl filled with popcorn kernels has made it easy for her to get the attention of her students.
Drawing as Social Play: Shared Meaning-Making in Young Children's Collective Drawing Activities
ERIC Educational Resources Information Center
Kukkonen, Tiina; Chang-Kredl, Sandra
2018-01-01
The ability to construct shared meaning with peers is important for young children's social and linguistic development. Previous studies have mainly focused on shared meaning-making within cooperative pretend play with little mention of other childhood activities that might promote intersubjectivity. This study investigated the group play that…
Favorite Children's Books for Vocal Exploration and Pitch-Matching Activities
ERIC Educational Resources Information Center
Cardany, Audrey Berger
2017-01-01
In this article, the author shares favorite children's books and stories for integrating language and music during shared-book experiences. The music activities described are aimed to contribute to the overall singing development for children in preschool and primary grades. Music and reading teachers will enjoy sharing these books with early…
Andrew B. Self; Andrew W. Ezell; Andrew J. Londo; John D. Hodges
2010-01-01
Oaks are an ecologically and economically important component of the southern landscape, and many landowners are opting to regenerate their lands with these species. Federal cost share programs, such as the Wetland Reserve Program (WRP), have increased public interest in afforestation of retired agricultural sites in the Lower Mississippi Alluvial Valley (LMAV). Acorns...
Bookmark this site. A guide to home care & hospice websites.
Sister Florence Maier; Hart, Amandie
2003-03-01
An information source like no other, the Internet is a place for communication, research, community building, and information sharing. As the Internet has grown in popularity, the number of sites providing useful information and networking has grown exponentially. The challenge to time strapped home care and hospice providers is finding those sites that provide the information you need to know and getting to that information quickly and easily.
Implementation for GREAT I Study.
1981-06-01
population centers where greater beneficial use is expected. ’Most of the sites selected are not owned by the Federal Government. Many factors could prevent ...have to be five to six times the dredged material volume. Berming is generally required to prevent encroachment beyond the placement site. The site...fish and wildlife and/ or recreation under its cost-sharing authorities (Public Law 89-72 and Code 710 Prgram ), including facilitating the
A Commander’s Strategy for Social Media
2011-01-01
information is passed across societies and around the world. The rapid spread of blogs, social networking sites , and media-sharing technology (such as...able to identify emerg- ing trends and patterns. Blogs and social networking sites could provide insight to any society where there is a significant...online community, particularly in societies with a relatively young population. The Department of State has effectively used social networking sites to
Zhu, Gao-Ru; Porter, John H; Xu, Xue-Gong
2011-06-01
In order to observe and understand long-term and large-scale ecological changes, the US National Science Foundation initiated a Long-Term Ecological Research (LTER) program in 1980. Over the past 30 years, the US LTER program has achieved advances in ecological and social science research, and in the development of site-based research infrastructure. This paper attributed the success of the program to five characteristics, i.e., 1) consistency of research topics and data across the network, 2) long-term time scale of both the research and the program, 3) flexibility in research content and funding procedures, 4) growth of LTER to include international partners, new disciplines such as social science, advanced research methods, and cooperation among sites, and 5) sharing of data and educational resources. The Virginia Coast Reserve LTER site was taken as an example to illustrate how the US LTER works at site level. Some suggestions were made on the China long-term ecological research, including strengthening institution construction, improving network and inter-site cooperation, emphasizing data quality, management, and sharing, reinforcing multidisciplinary cooperation, and expanding public influence.
The strategic case for establishing public-private partnerships in cancer care.
Holden, Debra J; Reiter, Kristin; O'Brien, Donna; Dalton, Kathleen
2015-10-14
In 2007, the National Cancer Institute (NCI) launched the NCI Community Cancer Centers Program (NCCCP) as a public-private partnership with community hospitals with a goal of advancing cancer care and research. In order to leverage federal dollars in a time of limited resources, matching funds from each participating hospital were required. The purpose of this paper is to examine hospitals' level of and rationale for co-investment in this partnership, and whether there is an association between hospitals' co-investment and achievement of strategic goals. Analysis using a comparative case study and micro-cost data was conducted as part of a comprehensive evaluation of the NCCCP pilot to determine the level of co-investment made in support of NCI's goals. In-person or telephone interviews with key informants were conducted at 10 participating hospital and system sites during the first and final years of implementation. Micro-cost data were collected annually from each site from 2007 to 2010. Self-reported data from each awardee are presented on patient volume and physician counts, while secondary data are used to examine the local Medicare market share. The rationale expressed by interviewees for participation in a public-private partnership with NCI included expectations of increased market share, higher patient volumes, and enhanced opportunities for cancer physician recruitment as a result of affiliation with the NCI. On average, hospitals invested resources into the NCCCP at a level exceeding $3 for every $1 of federal funds. Six sites experienced a statistically significant change in their Medicare market share. Cancer patient volume increased by as much as one-third from Year 1 to Year 3 for eight of the sites. Nine sites reported an increase in key cancer physician recruitment. Demonstrated investments in cancer care and research were associated with increases in cancer patient volume and perhaps in recruitment of key cancer physicians, but not in increased Medicare market share. Although the results reflect a small sample of hospitals, findings suggest that hospital executives believe there to be a strategic case for a public-private partnership as demonstrated through the NCCCP, which leveraged federal funds to support mutual goals for advancing cancer care and research.
2007-2008 Annual Progress Report for BPA Grant Exp Restore Walla Walla River Flow
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bower, Bob
WWBWC and its partners have been working on a wide variety of conservation and aquifer recharge related activities including: monitoring groundwater and surface water conditions, creating a geospatial database for the Walla Walla River valley (project focal area), expanding aquifer recharge testing at the HBDIC site and conducting an extensive outreach/education program by which to share the information, ideas and potential solutions to our current water management issues in this basin. This report is an outline of those activities and is accompanied by individual program-component (attached as appendices) reports for the areas that BPA is assisting to fund these on-the-groundmore » projects along with the innovative research and monitoring being done to further aquifer recharge as a water management tool for the Pacific Northwest.« less
Structure of a pectin methylesterase from Yersinia enterocolitica
Boraston, Alisdair B.; Abbott, D. Wade
2012-01-01
Pectin methylesterases (PMEs) are family 8 carbohydrate esterases (CE8s) which remove the methyl group from methylesterified galacturonic acid (GalA) residues within pectin. Although the role of pectinases such as PMEs within dedicated phytopathogens has been well established, the significance of homologous enzymes found within the genomes of human enteropathogens remains to be determined. Presented here is the low-resolution (3.5 Å) structure of the CE8 from Yersinia enterocolitica (YeCE8). The high degree of structural conservation in the topology of the active-site cleft and catalytic apparatus that is shared with a characterized PME from a bacterial phytopathogen (i) indicates that YeCE8 is active on methylated pectin and (ii) highlights a more prominent role for pectin utilization in Yersinia than in other enteropathogenic species. PMID:22297983
Miller, L A; Cochrane, D E; Feldberg, R S; Carraway, R E
1998-06-01
Neurotensin (NT), a peptide found in brain and several peripheral tissues, is a potent stimulus for mast cell secretion and its actions are blocked by the specific NT receptor antagonist, SR 48692. Subsequent to stimulation, NT is rapidly degraded by mast cell carboxypeptidase A (CPA). In the experiments described here, we tested for the involvement of CPA activity in the activation of mast cell secretion by the peptide, NT. Mast cells were isolated from the peritoneal and pleural cavities of rats, purified over metrizamide gradients and incubated at 37 degrees C in Locke solution or Locke containing the appropriate inhibitors. For some experiments, media derived from mast cells stimulated by compound 48/80 were used as a source of mast cell CPA activity. Treatment of mast cells with the highly specific peptide inhibitor of CPA derived from potato (PCI) inhibited histamine release in response to NT and NT8-13 (the biologically active region of NT). This inhibition required some 20 min to develop and was only partially reversed by a 20-min wash period. PCI (10 microM) did not inhibit histamine release in response to NT1-12, bradykinin, compound 48/80, the calcium ionophore, A23187, or anti-IgE serum. PCI also inhibited mast cell CPA activity. SR 48692, a highly selective antagonist of the brain NT receptor and of NT-stimulated mast cell secretion, also inhibited mast cell CPA activity as well as bovine pancreatic CPA activity in a concentration-dependent manner. It is suggested that the mast cell binding site for NT and the active site for CPA may share similar characteristics. The results are discussed in terms of NT mechanism of action on the mast cell.
Krall, J. R.; Hackstadt, A. J.; Peng, R. D.
2017-01-01
Exposure to particulate matter (PM) air pollution has been associated with a range of adverse health outcomes, including cardiovascular disease (CVD) hospitalizations and other clinical parameters. Determining which sources of PM, such as traffic or industry, are most associated with adverse health outcomes could help guide future recommendations aimed at reducing harmful pollution exposure for susceptible individuals. Information obtained from multisite studies, which is generally more precise than information from a single location, is critical to understanding how PM impacts health and to informing local strategies for reducing individual-level PM exposure. However, few methods exist to perform multisite studies of PM sources, which are not generally directly observed, and adverse health outcomes. We developed SHARE, a hierarchical modeling approach that facilitates reproducible, multisite epidemiologic studies of PM sources. SHARE is a two-stage approach that first summarizes information about PM sources across multiple sites. Then, this information is used to determine how community-level (i.e. county- or city-level) health effects of PM sources should be pooled to estimate regional-level health effects. SHARE is a type of population value decomposition that aims to separate out regional-level features from site-level data. Unlike previous approaches for multisite epidemiologic studies of PM sources, the SHARE approach allows the specific PM sources identified to vary by site. Using data from 2000–2010 for 63 northeastern US counties, we estimated regional-level health effects associated with short-term exposure to major types of PM sources. We found PM from secondary sulfate, traffic, and metals sources was most associated with CVD hospitalizations. PMID:28098412
Common capacity-limited neural mechanisms of selective attention and spatial working memory encoding
Fusser, Fabian; Linden, David E J; Rahm, Benjamin; Hampel, Harald; Haenschel, Corinna; Mayer, Jutta S
2011-01-01
One characteristic feature of visual working memory (WM) is its limited capacity, and selective attention has been implicated as limiting factor. A possible reason why attention constrains the number of items that can be encoded into WM is that the two processes share limited neural resources. Functional magnetic resonance imaging (fMRI) studies have indeed demonstrated commonalities between the neural substrates of WM and attention. Here we investigated whether such overlapping activations reflect interacting neural mechanisms that could result in capacity limitations. To independently manipulate the demands on attention and WM encoding within one single task, we combined visual search and delayed discrimination of spatial locations. Participants were presented with a search array and performed easy or difficult visual search in order to encode one, three or five positions of target items into WM. Our fMRI data revealed colocalised activation for attention-demanding visual search and WM encoding in distributed posterior and frontal regions. However, further analysis yielded two patterns of results. Activity in prefrontal regions increased additively with increased demands on WM and attention, indicating regional overlap without functional interaction. Conversely, the WM load-dependent activation in visual, parietal and premotor regions was severely reduced during high attentional demand. We interpret this interaction as indicating the sites of shared capacity-limited neural resources. Our findings point to differential contributions of prefrontal and posterior regions to the common neural mechanisms that support spatial WM encoding and attention, providing new imaging evidence for attention-based models of WM encoding. PMID:21781193
Adams, Samantha A
2011-04-01
In countries where the notion of "reflexive patients" dominates the health policy landscape, patients are increasingly encouraged to publicize their personal experiences with health services provision by reviewing hospitals and professionals on the web. The number of websites where patients can review one or more aspects of their care (and read reviews posted by others) is growing. These sites are an example of the practice of crowdsourcing, where applications that facilitate user-generated content solicit feedback from a given public; site administrators then use this feedback for product development, quality improvement and policy change. The research presented here examines such developments in the context of ongoing discussions about reflexive consumerism and increased transparency in healthcare. It draws on data from a three-year study of share-your-experience sites in the U.S., U.K., and The Netherlands. Data is taken primarily from a discourse analysis of four of the six sites under study, including patient reviews of institutions and professionals (n=450). Supplementary data from interviews with stakeholders related to the Dutch sites (n=15) is also used. This is the first known study of multiple share-your-experience websites in different countries. It shows that monitoring as "reflexive" behavior is not automatic, but is encouraged by website creators who, hoping to use the posts for other purposes, act as mediators between patients and other healthcare stakeholders. It further argues that patients demonstrate more reflexivity than some stakeholders realize, although not necessarily in the way that Giddens proposed. It concludes with the argument that the focus on reflexivity in healthcare means that not only institutions must be more transparent about their performance; patients are expected to be more transparent about their choices, as well. Copyright © 2011 Elsevier Ltd. All rights reserved.
AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform
Massett, Holly A.; Parreco, Linda K.; Padberg, Rose Mary; Richmond, Ellen S.; Rienzo, Marie E.; Leonard, Colleen E. Ryan; Quesenbery, Whitney; Killiam, H. William; Johnson, Lenora E.; Dilts, David M.
2011-01-01
Purpose: Present the design and initial evaluation of a unique, Web-enabled platform for the development of a community of practice around issues of oncology clinical trial accrual. Methods: The National Cancer Institute (NCI) conducted research with oncology professionals to identify unmet clinical trial accrual needs in the field. In response, a comprehensive platform for accrual resources, AccrualNet, was created by using an agile development process, storyboarding, and user testing. Literature and resource searches identified relevant content to populate the site. Descriptive statistics were tracked for resource and site usage. Use cases were defined to support implementation. Results: AccrualNet has five levels: (1) clinical trial macrostages (prestudy, active study, and poststudy); (2) substages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); (3) strategies for each substage; (4) multiple activities for each strategy; and (5) multiple resources for each activity. Since its launch, AccrualNet has had more than 45,000 page views, with the Tools & Resources, Conversations, and Training sections being the most viewed. Total resources have increased 69%, to 496 items. Analysis of articles in the site reveals that 22% are from two journals and 46% of the journals supplied a single article. To date, there are 29 conversations with 43 posts. Four use cases are discussed. Conclusion: AccrualNet represents a unique, centralized comprehensive-solution platform to systematically capture accrual knowledge for all stages of a clinical trial. It is designed to foster a community of practice by encouraging users to share additional strategies, resources, and ideas. PMID:22379429
AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform.
Massett, Holly A; Parreco, Linda K; Padberg, Rose Mary; Richmond, Ellen S; Rienzo, Marie E; Leonard, Colleen E Ryan; Quesenbery, Whitney; Killiam, H William; Johnson, Lenora E; Dilts, David M
2011-11-01
Present the design and initial evaluation of a unique, Web-enabled platform for the development of a community of practice around issues of oncology clinical trial accrual. The National Cancer Institute (NCI) conducted research with oncology professionals to identify unmet clinical trial accrual needs in the field. In response, a comprehensive platform for accrual resources, AccrualNet, was created by using an agile development process, storyboarding, and user testing. Literature and resource searches identified relevant content to populate the site. Descriptive statistics were tracked for resource and site usage. Use cases were defined to support implementation. ACCRUALNET HAS FIVE LEVELS: (1) clinical trial macrostages (prestudy, active study, and poststudy); (2) substages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); (3) strategies for each substage; (4) multiple activities for each strategy; and (5) multiple resources for each activity. Since its launch, AccrualNet has had more than 45,000 page views, with the Tools & Resources, Conversations, and Training sections being the most viewed. Total resources have increased 69%, to 496 items. Analysis of articles in the site reveals that 22% are from two journals and 46% of the journals supplied a single article. To date, there are 29 conversations with 43 posts. Four use cases are discussed. AccrualNet represents a unique, centralized comprehensive-solution platform to systematically capture accrual knowledge for all stages of a clinical trial. It is designed to foster a community of practice by encouraging users to share additional strategies, resources, and ideas.
Zúñiga, Matías A; Alderete, Joel B; Jaña, Gonzalo A; Jiménez, Verónica A
2017-07-01
Peloruside A (PLA) and Laulimalide (LAU) are novel microtubule-stabilizing agents with promising properties against different cancer types. These ligands share a non-taxoid binding site at the outer surface of β-tubulin and promote microtubule stabilization by bridging two adjacent αβ-tubulin dimers from parallel protofilaments. Recent site-directed mutagenesis experiments confirmed the existence of a unique β-tubulin site mutation (Gln293Met) that specifically increased the activity of PLA and caused resistance to LAU, without affecting the stability of microtubules in the absence of the ligands. In this work, fully atomistic molecular dynamics simulations were carried out to examine the PLA and LAU association with native and mutated αβ-tubulin in the search for structural and energetic evidence to explain the role of Gln293Met mutation on determining the activity of these ligands. Our results revealed that Gln293Met mutation induced the loss of relevant LAU-tubulin contacts but exerted negligible changes in the interaction networks responsible for PLA-tubulin association. Binding free energy calculations (MM/GBSA and MM/PBSA), and weak interaction analysis (aNCI) predicted an increased affinity for PLA, and a weakened association for LAU after mutation, thus suggesting that Gln293Met mutation exerts its action by a modulation of drug-tubulin interactions. These results are valuable to increase understanding about PLA and LAU activity and to assist the future design of novel agents targeting the PLA/LAU binding pocket.
NASA Astrophysics Data System (ADS)
Zúñiga, Matías A.; Alderete, Joel B.; Jaña, Gonzalo A.; Jiménez, Verónica A.
2017-07-01
Peloruside A (PLA) and Laulimalide (LAU) are novel microtubule-stabilizing agents with promising properties against different cancer types. These ligands share a non-taxoid binding site at the outer surface of β-tubulin and promote microtubule stabilization by bridging two adjacent αβ-tubulin dimers from parallel protofilaments. Recent site-directed mutagenesis experiments confirmed the existence of a unique β-tubulin site mutation (Gln293Met) that specifically increased the activity of PLA and caused resistance to LAU, without affecting the stability of microtubules in the absence of the ligands. In this work, fully atomistic molecular dynamics simulations were carried out to examine the PLA and LAU association with native and mutated αβ-tubulin in the search for structural and energetic evidence to explain the role of Gln293Met mutation on determining the activity of these ligands. Our results revealed that Gln293Met mutation induced the loss of relevant LAU-tubulin contacts but exerted negligible changes in the interaction networks responsible for PLA-tubulin association. Binding free energy calculations (MM/GBSA and MM/PBSA), and weak interaction analysis (aNCI) predicted an increased affinity for PLA, and a weakened association for LAU after mutation, thus suggesting that Gln293Met mutation exerts its action by a modulation of drug-tubulin interactions. These results are valuable to increase understanding about PLA and LAU activity and to assist the future design of novel agents targeting the PLA/LAU binding pocket.
Sørensen, J; Primdahl, J; Horn, H C; Hørslev-Petersen, K
2015-01-01
To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse consultations. Effectiveness measures included disease activity (Disease Activity Score based on 28 joint counts and C-reactive protein, DAS28-CRP), functional status (Health Assessment Questionnaire, HAQ), and health-related quality of life (EuroQol EQ-5D). Cost measures included activities in outpatient clinics and general practice, prescription and non-prescription medicine, dietary supplements, other health-care resources, and complementary and alternative care. Measures of effectiveness and costs were collected by self-reported questionnaires at inclusion and after 12 and 24 months. Incremental cost-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10,000 per quality-adjusted life year (QALY) threshold, shared care and nurse care were cost-effective with more than 90% probability. Nurse care was cost-effective in comparison with shared care with 75% probability. Shared care and nurse care seem to cost less but provide broadly similar health outcomes compared with rheumatologist outpatient care. However, it is still uncertain whether nurse care and shared care are cost-effective in comparison with rheumatologist outpatient care.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shaw, W.D. Jr.
1985-01-01
The Adirondack State Park has been hit especially hard by acid precipitation. Acid precipitation impacts particular species of fish at various high altitudes sites in the park. The author estimates consumer surplus measures for changes in a variable to proxy the stock size of these species at specific sites. To do this he first estimates the individual's demand for a recreation site as a function of site prices and the site's characteristics. The demand function for the individual is derived from a utility function. A travel cost approach is used to estimate an individual's share of total fishing time spentmore » at a five fishing site. The shares are estimated by maximum likelihood and the results indicate that price and the three characteristics do explain the allocation of the individual's time spent at the various sites selected for the analysis. Finally, consumer surplus measures for a reduction in the catch rates of the species most likely to be affected by Acid Precipitation are calculated. The meaning of these measures in the context of a model that assumes weak separability is examined. These reductions in catch rates can be linked to changes in the level of Acid Precipitation in the Park, and this provides us with a method for quantifying the impact of acid precipitation on recreation fishing.« less
Plasmid partition system of the P1par family from the pWR100 virulence plasmid of Shigella flexneri.
Sergueev, Kirill; Dabrazhynetskaya, Alena; Austin, Stuart
2005-05-01
P1par family members promote the active segregation of a variety of plasmids and plasmid prophages in gram-negative bacteria. Each has genes for ParA and ParB proteins, followed by a parS partition site. The large virulence plasmid pWR100 of Shigella flexneri contains a new P1par family member: pWR100par. Although typical parA and parB genes are present, the putative pWR100parS site is atypical in sequence and organization. However, pWR100parS promoted accurate plasmid partition in Escherichia coli when the pWR100 Par proteins were supplied. Unique BoxB hexamer motifs within parS define species specificities among previously described family members. Although substantially different from P1parS from the P1 plasmid prophage of E. coli, pWR100parS has the same BoxB sequence. As predicted, the species specificity of the two types proved identical. They also shared partition-mediated incompatibility, consistent with the proposed mechanistic link between incompatibility and species specificity. Among several informative sequence differences between pWR100parS and P1parS is the presence of a 21-bp insert at the center of the pWR100parS site. Deletion of this insert left much of the parS activity intact. Tolerance of central inserts with integral numbers of helical DNA turns reflects the critical topology of these sites, which are bent by binding the host IHF protein.
NASA Astrophysics Data System (ADS)
Kjeldsen, Frank; Savitski, Mikhail M.; Adams, Christopher M.; Zubarev, Roman A.
2006-06-01
Location of protonated sites in electrospray-ionized gas-phase peptides and proteins was performed with tandem mass spectrometry using ion activation by both electron capture dissociation (ECD) and collisional activation dissociation (CAD). Charge-carrying sites were assigned based on the increment in the charge state of fragment ions compared to that of the previous fragment in the same series. The property of ECD to neutralize preferentially the least basic site was confirmed by the analysis of three thousand ECD mass spectra of doubly charged tryptic peptides. Multiply charged cations of bradykinin, neurotensin and melittin were studied in detail. For n+ precursors, ECD revealed the positions of (n - 1) most basic sites, while CAD could in principle locate alln charges. However, ECD introduced minimal proton mobilization and produced more conclusive data than CAD, for which N- and C-terminal data often disagreed. Consistent with the dominance of one charge conformer and its preservation in ECD, the average charge states of complementary fragments of n+ ions almost always added up to (n - 1)+, while the similar figure in CAD often deviated from n+, indicating extensive charge isomerization under collisional excitation. For bradykinin and neurotensin, the charge assignments were largely in agreement with the intrinsic gas-phase basicity of the respective amino acid residues. For melittin ions in higher charge states, ECD revealed the charging at both intrinsically basic as well as at less basic residues, which was attributed to charge sharing with other groups due to the presence of secondary and higher order structures in this larger polypeptide.
You, Ye-Ming; Wang, Juan; Sun, Xiao-Lu; Tang, Zuo-Xin; Zhou, Zhi-Yong; Sun, Osbert Jianxin
2016-03-01
Understanding the controls on soil carbon dynamics is crucial for modeling responses of ecosystem carbon balance to global change, yet few studies provide explicit knowledge on the direct and indirect effects of forest stands on soil carbon via microbial processes. We investigated tree species, soil, and site factors in relation to soil carbon density and mineralization in a temperate forest of central China. We found that soil microbial biomass and community structure, extracellular enzyme activities, and most of the site factors studied varied significantly across contrasting forest types, and that the associations between activities of soil extracellular enzymes and microbial community structure appeared to be weak and inconsistent across forest types, implicating complex mechanisms in the microbial regulation of soil carbon metabolism in relation to tree species. Overall, variations in soil carbon density and mineralization are predominantly accounted for by shared effects of tree species, soil, microclimate, and microbial traits rather than the individual effects of the four categories of factors. Our findings point to differential controls on soil carbon density and mineralization among contrasting forest types and highlight the challenge to incorporate microbial processes for constraining soil carbon dynamics in global carbon cycle models.
You, Ye-Ming; Wang, Juan; Sun, Xiao-Lu; Tang, Zuo-Xin; Zhou, Zhi-Yong; Sun, Osbert Jianxin
2016-01-01
Understanding the controls on soil carbon dynamics is crucial for modeling responses of ecosystem carbon balance to global change, yet few studies provide explicit knowledge on the direct and indirect effects of forest stands on soil carbon via microbial processes. We investigated tree species, soil, and site factors in relation to soil carbon density and mineralization in a temperate forest of central China. We found that soil microbial biomass and community structure, extracellular enzyme activities, and most of the site factors studied varied significantly across contrasting forest types, and that the associations between activities of soil extracellular enzymes and microbial community structure appeared to be weak and inconsistent across forest types, implicating complex mechanisms in the microbial regulation of soil carbon metabolism in relation to tree species. Overall, variations in soil carbon density and mineralization are predominantly accounted for by shared effects of tree species, soil, microclimate, and microbial traits rather than the individual effects of the four categories of factors. Our findings point to differential controls on soil carbon density and mineralization among contrasting forest types and highlight the challenge to incorporate microbial processes for constraining soil carbon dynamics in global carbon cycle models. PMID:26925871
Practices in Code Discoverability: Astrophysics Source Code Library
NASA Astrophysics Data System (ADS)
Allen, A.; Teuben, P.; Nemiroff, R. J.; Shamir, L.
2012-09-01
Here we describe the Astrophysics Source Code Library (ASCL), which takes an active approach to sharing astrophysics source code. ASCL's editor seeks out both new and old peer-reviewed papers that describe methods or experiments that involve the development or use of source code, and adds entries for the found codes to the library. This approach ensures that source codes are added without requiring authors to actively submit them, resulting in a comprehensive listing that covers a significant number of the astrophysics source codes used in peer-reviewed studies. The ASCL now has over 340 codes in it and continues to grow. In 2011, the ASCL has on average added 19 codes per month. An advisory committee has been established to provide input and guide the development and expansion of the new site, and a marketing plan has been developed and is being executed. All ASCL source codes have been used to generate results published in or submitted to a refereed journal and are freely available either via a download site or from an identified source. This paper provides the history and description of the ASCL. It lists the requirements for including codes, examines the advantages of the ASCL, and outlines some of its future plans.
Developing Governance for Federated Community-based EHR Data Sharing
Lin, Ching-Ping; Stephens, Kari A.; Baldwin, Laura-Mae; Keppel, Gina A.; Whitener, Ron J.; Echo-Hawk, Abigail; Korngiebel, Diane
2014-01-01
Bi-directional translational pathways between scientific discoveries and primary care are crucial for improving individual patient care and population health. The Data QUEST pilot project is a program supporting data sharing amongst community based primary care practices and is built on a technical infrastructure to share electronic health record data. We developed a set of governance requirements from interviewing and collaborating with partner organizations. Recommendations from our partner organizations included: 1) partner organizations can physically terminate the link to the data sharing network and only approved data exits the local site; 2) partner organizations must approve or reject each query; 3) partner organizations and researchers must respect local processes, resource restrictions, and infrastructures; and 4) partner organizations can be seamlessly added and removed from any individual data sharing query or the entire network. PMID:25717404
Nakhasi, Atul; Shen, Album Xiaotian; Passarella, Ralph Joseph; Appel, Lawrence J; Anderson, Cheryl Am
2014-06-16
The US Centers for Disease Control and Prevention have identified a lack of encouragement, support, or companionship from family and friends as a major barrier to physical activity. To overcome this barrier, online social networks are now actively leveraging principles of companion social support in novel ways. The aim was to evaluate the functionality, features, and usability of existing online social networks which seek to increase physical activity and fitness among users by connecting them to physical activity partners, not just online, but also face-to-face. In September 2012, we used 3 major databases to identify the website addresses for relevant online social networks. We conducted a Google search using 8 unique keyword combinations: the common keyword "find" coupled with 1 of 4 prefix terms "health," "fitness," "workout," or "physical" coupled with 1 of 2 stem terms "activity partners" or "activity buddies." We also searched 2 prominent technology start-up news sites, TechCrunch and Y Combinator, using 2 unique keyword combinations: the common keyword "find" coupled with 1 of 2 stem terms "activity partners" and "activity buddies." Sites were defined as online social health activity networks if they had the ability to (1) actively find physical activity partners or activities for the user, (2) offer dynamic, real-time tracking or sharing of social activities, and (3) provide virtual profiles to users. We excluded from our analysis sites that were not Web-based, publicly available, in English, or free. Of the 360 initial search results, we identified 13 websites that met our complete criteria of an online social health activity network. Features such as physical activity creation (13/13, 100%) and private messaging (12/13, 92%) appeared almost universally among these websites. However, integration with Web 2.0 technologies such as Facebook and Twitter (9/13, 69%) and the option of direct event joining (8/13, 62%) were not as universally present. Largely absent were more sophisticated features that would enable greater usability, such as interactive engagement prompts (3/13, 23%) and system-created best fit activities (3/13, 23%). Several major online social networks that connect users to physical activity partners currently exist and use standardized features to achieve their goals. Future research is needed to better understand how users utilize these features and how helpful they truly are.
Recreational use in dispersed public lands measured using social media data and on-site counts.
Fisher, David M; Wood, Spencer A; White, Eric M; Blahna, Dale J; Lange, Sarah; Weinberg, Alex; Tomco, Michael; Lia, Emilia
2018-09-15
Outdoor recreation is one of many important benefits provided by public lands. Data on recreational use are critical for informing management of recreation resources, however, managers often lack actionable information on visitor use for large protected areas that lack controlled access points. The purpose of this study is to explore the potential for social media data (e.g., geotagged images shared on Flickr and trip reports shared on a hiking forum) to provide land managers with useful measures of recreational use to dispersed areas, and to provide lessons learned from comparing several more traditional counting methods. First, we measure daily and monthly visitation rates to individual trails within the Mount Baker-Snoqualmie National Forest (MBSNF) in western Washington. At 15 trailheads, we compare counts of hikers from infrared sensors, timelapse cameras, and manual on-site counts, to counts based on the number of shared geotagged images and trip reports from those locations. Second, we measure visitation rates to each National Forest System (NFS) unit across the US and compare annual measurements derived from the number of geotagged images to estimates from the US Forest Service National Visitor Use Monitoring Program. At both the NFS unit and the individual-trail scales, we found strong correlations between traditional measures of recreational use and measures based on user-generated content shared on the internet. For national forests in every region of the country, correlations between official Forest Service statistics and geotagged images ranged between 55% and 95%. For individual trails within the MBSNF, monthly visitor counts from on-site measurements were strongly correlated with counts from geotagged images (79%) and trip reports (91%). The convenient, cost-efficient and timely nature of collecting and analyzing user-generated data could allow land managers to monitor use over different seasons of the year and at sites and scales never previously monitored, contributing to a more comprehensive understanding of recreational use patterns and values. Copyright © 2018 Elsevier Ltd. All rights reserved.
A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR).
Leyendecker, Gerhard; Wildt, Ludwig
2011-03-01
Pelvic endometriosis, deeply infiltrating endometriosis and uterine adenomyosis share a common pathophysiology and may be integrated into the physiological mechanism and new nosological concept of 'tissue injury and repair' (TIAR) and may, in this context, just represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive reproductive organ. The acronym TIAR describes a fundamental and apparently ubiquitous biological system that becomes operative in mesenchymal tissues following tissue injury and, upon activation, results in the local production of estradiol. Endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatisations, with activation of the TIAR mechanism. With ongoing traumatisations, such sites of inflammation might accumulate and the increasingly produced estrogens interfere in a paracrine fashion with ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt autotraumatisation of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis a causal event early in the reproductive period of life must be postulated, rapidly leading to archimetral hyperestrogenism and uterine hyperperistalsis. In late premenopausal adenomyosis such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life accumulates to the same extent of microtraumatisation. With activation of the TIAR mechanism followed by chronic inflammation and infiltrative growth, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principal the same pathophysiology.
Wang, Qingqing; Imam, Mustapha Umar; Yida, Zhang; Wang, Fudi
2017-01-01
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the nuclear receptor superfamily of ligand-inducible transcription factors that regulate adipogenesis, lipid metabolism, cell proliferation, inflammation and insulin sensitization. Abnormalities in PPARγ signaling have been associated with obesity, diabetes and cancer. The use of agonists to manage these diseases has been limited by their side effects. Accordingly, dual or pan agonists targeting the PPARα or PPARα and PPARδ, respectively, in addition to the PPARγ have been developed to overcome these side effects. This review details the shared PPARγ-dependent mechanisms between obesity-related cancers and diabetes and their potential therapeutic values. We performed a systematic literature search through pubmed, Scopus and google scholar for articles on PPARγ-dependent signaling in diabetes or cancer. There is growing co-occurrence of obesity-related cancers and diabetes, necessitating the use of effective therapies with the least amount of side effects for concurrent management of these diseases, by targeting potentially shared PPARγ-dependent mechanisms including abnormalities of the wnt/β-catenin, lysosomal acid lipase, inflammatory and cell cycle pathways, and the plasminogen activator system. Taking advantage of the multiple docking sites of the PPARγ and the pleiotropic nature of its signaling, structure-activity relationship and molecular docking studies have provided insights into designer PPARγ agonists or dual PPARα/γ agonists that modulate PPARγ signaling and negate side effects of full PPARγ agonists. Effective therapies, possibly devoid of side effects, for concurrent management of obesity-related cancers and diabetes can be developed through diligent structure-activity and molecular docking studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Engaging Alaskan Students in Cryospheric Research
NASA Astrophysics Data System (ADS)
Yoshikawa, K.; Sparrow, E. B.; Kopplin, M.
2011-12-01
The Permafrost/Active Layer Monitoring Program is an ongoing project, which builds on work begun in 2005 to establish long-term permafrost and active layer monitoring sites adjacent to schools in Alaskan communities and in the circumpolar permafrost region. Currently, there are about 200 schools in Alaska involved in the project including also Denali National Park and Preserve. The project has both scientific and outreach components. The monitoring sites collect temperature data on permafrost, and the length and depth of the active layer (the layer above the permafrost that thaws during summer and freezes again during winter). To ensure scientific integrity, the scientist installed all of the monitoring instruments and selected the sites representative of the surrounding biome and thermal conditions. This is a unique collaboration opportunity in that 1) uses scientifically accurate instruments, 2) is scientist led and supervised including instrumentation set-up and data quality check, 3)has teacher/student organized observation network, 4) increased spatial scale of monitoring sites that covers all of the Alaskan communities. Most of the monitoring sites are located in remote communities, where the majority of residents depend on a subsistence lifestyle. Changes in climate, length of seasons, and permafrost conditions directly impact natural resources and subsistence activities. Changes in permafrost conditions also affect local ecosystems and hydrological regimes, and can influence the severity of natural disasters. In addition to extending our knowledge of the arctic environment, the program involves school-age students. Several students have been using the data for their projects and have been inspired to continue their studies. The data gathered from these stations are shared with other schools and made available to the public through our web site (http://www.uaf.edu/permafrost). Also communities have increasingly become interested in this project not only as an educational program, but also for its implications for disasters such as mud slides, loss of food storage in the ground capability, water pipes bursting from ground freezing at lower depths. Challenges in education outreach include the high cost (dollars and time) of reaching the remote study sites scattered all over the vast Alaskan landscape and how to increase understanding of the science concepts in the long-term study of permafrost and active layer, by students. In addition to the scientific measurement protocols and learning activities developed, videos of the adventures of a superhero Tunnel Man, were developed, produced and are made available on the project website as well as on YouTube. Through this project, students in remote Alaskan communities learn science in a way that is meaningful to their daily lives. In addition, they experience research participation within a larger scientific community, expanding their worldview.
12 CFR 708a.305 - Disclosures and communications to members.
Code of Federal Regulations, 2011 CFR
2011-01-01
... to any matter, including a general economic, political, racial, religious, social, or similar cause...) If a credit union posts merger-related information or material on its Web site, then it must simultaneously make a portion of its Web site available free of charge to its members to post and share their...
12 CFR 708a.4 - Disclosures and communications to members.
Code of Federal Regulations, 2011 CFR
2011-01-01
... to any matter, including a general economic, political, racial, religious, social, or similar cause...) If a credit union posts conversion-related information or material on its Web site, then it must simultaneously make a portion of its Web site available free of charge to its members to post and share their...
Understanding and Designing for Interactional Privacy Needs within Social Networking Sites
ERIC Educational Resources Information Center
Wisniewski, Pamela J.
2012-01-01
"Interpersonal boundary regulation" is a way to optimize social interactions when sharing and connecting through Social Networking Sites (SNSs). The theoretical foundation of much of my research comes from Altman's work on privacy management in the physical world. Altman believed that "we should attempt to design responsive…
A Comparison of Regional and SiteSpecific Volume Estimation Equations
Joe P. McClure; Jana Anderson; Hans T. Schreuder
1987-01-01
Regression equations for volume by region and site class were examined for lobiolly pine. The regressions for the Coastal Plain and Piedmont regions had significantly different slopes. The results shared important practical differences in percentage of confidence intervals containing the true total volume and in percentage of estimates within a specific proportion of...
George Mason University's Elementary PDS Program: Embracing Innovation
ERIC Educational Resources Information Center
Groth, Lois A.; Parker, Audra; Parsons, Seth A.; Sprague, Deborah; Levine Brown, Elizabeth; Baker, Courtney; Suh, Jennifer
2017-01-01
This article describes the Mason Elementary PDS Network (PDS Network), a multi-district network of clinical field sites, embracing collaboration with key stakeholders as a means to broaden its impact on the education profession and the larger community. The Mason Elementary PDS Network includes 30 elementary school sites with a shared commitment…
Third Grade Written Narratives: A Cross-Linguistic Study.
ERIC Educational Resources Information Center
Gregory, George Ann
A study examined what a third grader might understand about composing a common genre like the narrative, given the degree of variance among approaches and experience. Data were collected from different school sites over a period of several years. These sites shared common geographical areas: three schools were located in the Sonoran desert shared…
Fangirls as Teachers: Examining Pedagogic Discourse in an Online Fan Site
ERIC Educational Resources Information Center
Lammers, Jayne C.
2013-01-01
Videogames, such as "The Sims," are a digital media passion drawing adolescents to online spaces where they create and share content. This article explores how discourses and expectations are taught in one online, videogame-related fan site of adolescents who read and write "Sims" fan fiction. Using Bernstein's pedagogic…
Fialkowski, Marie K.; Yamanaka, Ashley; Wilkens, Lynne R.; Braun, Kathryn L.; Butel, Jean; Ettienne, Reynolette; McGlone, Katalina; Remengesau, Shelley; Power, Julianne M.; Johnson, Emihner; Gilmatam, Daisy; Fleming, Travis; Acosta, Mark; Belyeu-Camacho, Tayna; Shomour, Moria; Sigrah, Cecilia; Nigg, Claudio; Novotny, Rachel
2016-01-01
The US Affiliated Pacific region's childhood obesity prevalence has reached epidemic proportions. To guide program and policy development, a multi-site study was initiated, in collaboration with partners from across the region, to gather comprehensive information on the regional childhood obesity prevalence. The environmental and cultural diversity of the region presented challenges to recruiting for and implementing a shared community-based, public health research program. This paper presents the strategies used to recruit families with young children (n = 5775 for children 2 – 8 years old) for obesity-related measurement across eleven jurisdictions in the US Affiliated Pacific Region. Data were generated by site teams that provided summaries of their recruitment strategies and lessons learned. Conducting this large multi-site prevalence study required considerable coordination, time and flexibility. In every location, local staff knowledgeable of the community was hired to lead recruitment, and participant compensation reflected jurisdictional appropriateness (e.g., gift cards, vouchers, or cash). Although recruitment approaches were site-specific, they were predominantly school-based or a combination of school- and community-based. Lessons learned included the importance of organization buy-in; communication, and advance planning; local travel and site peculiarities; and flexibility. Future monitoring of childhood obesity prevalence in the region should consider ways to integrate measurement activities into existing organizational infrastructures for sustainability and cost-effectiveness, while meeting programmatic (e.g. study) goals. PMID:29546153
Nakajima, Keiji; Yamashita, Atsuko; Akama, Hiroyuki; Nakatsu, Toru; Kato, Hiroaki; Hashimoto, Takashi; Oda, Jun’ichi; Yamada, Yasuyuki
1998-01-01
A pair of tropinone reductases (TRs) share 64% of the same amino acid residues and belong to the short-chain dehydrogenase/reductase family. In the synthesis of tropane alkaloids in several medicinal plants, the TRs reduce a carbonyl group of an alkaloid intermediate, tropinone, to hydroxy groups with different diastereomeric configurations. To clarify the structural basis for their different reaction stereospecificities, we determined the crystal structures of the two enzymes at 2.4- and 2.3-Å resolutions. The overall folding of the two enzymes was almost identical. The conservation was not confined within the core domains that are conserved within the protein family but extended outside the core domain where each family member has its characteristic structure. The binding sites for the cofactor and the positions of the active site residues were well conserved between the two TRs. The substrate binding site was composed mostly of hydrophobic amino acids in both TRs, but the presence of different charged residues conferred different electrostatic environments on the two enzymes. A modeling study indicated that these charged residues play a major role in controlling the binding orientation of tropinone within the substrate binding site, thereby determining the stereospecificity of the reaction product. The results obtained herein raise the possibility that in certain cases different stereospecificities can be acquired in enzymes by changing a few amino acid residues within substrate binding sites. PMID:9560196
Fialkowski, Marie K; Yamanaka, Ashley; Wilkens, Lynne R; Braun, Kathryn L; Butel, Jean; Ettienne, Reynolette; McGlone, Katalina; Remengesau, Shelley; Power, Julianne M; Johnson, Emihner; Gilmatam, Daisy; Fleming, Travis; Acosta, Mark; Belyeu-Camacho, Tayna; Shomour, Moria; Sigrah, Cecilia; Nigg, Claudio; Novotny, Rachel
2016-01-01
The US Affiliated Pacific region's childhood obesity prevalence has reached epidemic proportions. To guide program and policy development, a multi-site study was initiated, in collaboration with partners from across the region, to gather comprehensive information on the regional childhood obesity prevalence. The environmental and cultural diversity of the region presented challenges to recruiting for and implementing a shared community-based, public health research program. This paper presents the strategies used to recruit families with young children (n = 5775 for children 2 - 8 years old) for obesity-related measurement across eleven jurisdictions in the US Affiliated Pacific Region. Data were generated by site teams that provided summaries of their recruitment strategies and lessons learned. Conducting this large multi-site prevalence study required considerable coordination, time and flexibility. In every location, local staff knowledgeable of the community was hired to lead recruitment, and participant compensation reflected jurisdictional appropriateness (e.g., gift cards, vouchers, or cash). Although recruitment approaches were site-specific, they were predominantly school-based or a combination of school- and community-based. Lessons learned included the importance of organization buy-in; communication, and advance planning; local travel and site peculiarities; and flexibility. Future monitoring of childhood obesity prevalence in the region should consider ways to integrate measurement activities into existing organizational infrastructures for sustainability and cost-effectiveness, while meeting programmatic (e.g. study) goals.
Launch Vehicle Control Center Architectures
NASA Technical Reports Server (NTRS)
Watson, Michael D.; Epps, Amy; Woodruff, Van; Vachon, Michael Jacob; Monreal, Julio; Levesque, Marl; Williams, Randall; Mclaughlin, Tom
2014-01-01
Launch vehicles within the international community vary greatly in their configuration and processing. Each launch site has a unique processing flow based on the specific launch vehicle configuration. Launch and flight operations are managed through a set of control centers associated with each launch site. Each launch site has a control center for launch operations; however flight operations support varies from being co-located with the launch site to being shared with the space vehicle control center. There is also a nuance of some having an engineering support center which may be co-located with either the launch or flight control center, or in a separate geographical location altogether. A survey of control center architectures is presented for various launch vehicles including the NASA Space Launch System (SLS), United Launch Alliance (ULA) Atlas V and Delta IV, and the European Space Agency (ESA) Ariane 5. Each of these control center architectures shares some similarities in basic structure while differences in functional distribution also exist. The driving functions which lead to these factors are considered and a model of control center architectures is proposed which supports these commonalities and variations.
Berntsson, Ronnie Per-Arne; Peng, Lisheng; Svensson, Linda Marie; Dong, Min; Stenmark, Pål
2013-09-03
Botulinum neurotoxins (BoNTs) can cause paralysis at exceptionally low concentrations and include seven serotypes (BoNT/A-G). The chimeric BoNT/DC toxin has a receptor binding domain similar to the same region in BoNT/C. However, BoNT/DC does not share protein receptor with BoNT/C. Instead, it shares synaptotagmin (Syt) I and II as receptors with BoNT/B, despite their low sequence similarity. Here, we present the crystal structures of the binding domain of BoNT/DC in complex with the recognition domains of its protein receptors, Syt-I and Syt-II. The structures reveal that BoNT/DC possesses a Syt binding site, distinct from the established Syt-II binding site in BoNT/B. Structure-based mutagenesis further shows that hydrophobic interactions play a key role in Syt binding. The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs. Copyright © 2013 Elsevier Ltd. All rights reserved.
2004-02-19
KENNEDY SPACE CENTER, FLA. - NASA Administrator Sean O’Keefe (center) listens to Congressman Tom Feeney (second from left) during a tour of the Central Florida Research Park, near Orlando. At right is U.S. Congressman Dave Weldon. Central Florida leaders are proposing the research park as the site for the new NASA Shared Services Center. The center would centralize NASA’s payroll, accounting, human resources, facilities and procurement offices that are now handled at each field center. The consolidation is part of the One NASA focus. Six sites around the U.S. are under consideration by NASA.
ERIC Educational Resources Information Center
Kanters, Michael A.; Bocarro, Jason N.; Filardo, Mary; Edwards, Michael B.; McKenzie, Thomas L.; Floyd, Myron F.
2014-01-01
Background: Partnerships between school districts and community-based organizations to share school facilities during afterschool hours can be an effective strategy for increasing physical activity. However, the perceived cost of shared use has been noted as an important reason for restricting community access to schools. This study examined…
Getting It Together: Notes toward a Shared Future for NCTE and CCCC
ERIC Educational Resources Information Center
Gilyard, Keith
2011-01-01
In this article, the author shares his notes toward a shared future for National Council of Teachers of English (NCTE) and Conference on College Composition and Communication (CCCC). He discusses how activism has been at the heart of both organizations, how language activism in particular has separated NCTE and CCCC--and brought them together, and…
Identification of a putative binding site critical for general anesthetic activation of TRPA1.
Ton, Hoai T; Phan, Thieu X; Abramyan, Ara M; Shi, Lei; Ahern, Gerard P
2017-04-04
General anesthetics suppress CNS activity by modulating the function of membrane ion channels, in particular, by enhancing activity of GABA A receptors. In contrast, several volatile (isoflurane, desflurane) and i.v. (propofol) general anesthetics excite peripheral sensory nerves to cause pain and irritation upon administration. These noxious anesthetics activate transient receptor potential ankyrin repeat 1 (TRPA1), a major nociceptive ion channel, but the underlying mechanisms and site of action are unknown. Here we exploit the observation that pungent anesthetics activate mammalian but not Drosophila TRPA1. Analysis of chimeric Drosophila and mouse TRPA1 channels reveal a critical role for the fifth transmembrane domain (S5) in sensing anesthetics. Interestingly, we show that anesthetics share with the antagonist A-967079 a potential binding pocket lined by residues in the S5, S6, and the first pore helix; isoflurane competitively disrupts A-967079 antagonism, and introducing these mammalian TRPA1 residues into dTRPA1 recapitulates anesthetic agonism. Furthermore, molecular modeling predicts that isoflurane and propofol bind to this pocket by forming H-bond and halogen-bond interactions with Ser-876, Met-915, and Met-956. Mutagenizing Met-915 or Met-956 selectively abolishes activation by isoflurane and propofol without affecting actions of A-967079 or the agonist, menthol. Thus, our combined experimental and computational results reveal the potential binding mode of noxious general anesthetics at TRPA1. These data may provide a structural basis for designing drugs to counter the noxious and vasorelaxant properties of general anesthetics and may prove useful in understanding effects of anesthetics on related ion channels.
Alquezar-Planas, David E.; Ishida, Yasuko; Courtiol, Alexandre; Timms, Peter; Johnson, Rebecca N.; Lenz, Dorina; Helgen, Kristofer M.; Roca, Alfred L.; Hartman, Stefanie
2016-01-01
Background. Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV) is currently invading the germline of the koala (Phascolarctos cinereus) and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized. Results. To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS) and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW) koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized. Conclusions. Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small. PMID:27069793
User-driven conversations about dialysis through Facebook: A qualitative thematic analysis.
Ahmed, Salim; Haines-Saah, Rebecca J; Afzal, Arfan R; Tam-Tham, Helen; Al Mamun, Mohammad; Hemmelgarn, Brenda R; Turin, Tanvir C
2017-04-01
As one of the most popular social networking sites in the world, Facebook has strong potential to enable peer support and the user-driven sharing of health information. We carried out a qualitative thematic analysis of the wall posts of a public Facebook group focused on dialysis to identify some of the major themes discussed. We searched Facebook using the word 'dialysis'. A Facebook group (Dialysis Discussion Uncensored) with the highest number of members was selected amongst publicly available forums related to dialysis and operated in English (http://www.facebook.com/groups/DialysisUncensored). Two researchers independently extracted information on features of the group including purpose, group members and the user-generated posts on the group wall. Posts were further analysed to develop major themes. Characteristics of a Facebook group based on its participants and activities are presented. Three themes are described with representative quotations. In a period of 2 weeks, we found 1257 wall posts with total of 31 636 likes and 15 972 comments. All messages were in English, and the majority of the participants were dialysis patients. However, we observed the participation of family members and care providers as well. Posts were categorized into three major themes: sharing information, seeking and providing emotional and social support and sharing experience. Findings of this study provide an example of how a social networking platform can enable patients and their families to share information and to encourage peer-based support for managing dialysis-related experiences. © 2016 Asian Pacific Society of Nephrology.
Martin, Kate; Webber, Helen; Craven, Michael P; Hollis, Chris; Deighton, Jessica; Law, Roslyn; Fonagy, Peter; Wolpert, Miranda
2017-01-01
Background Evidence suggests that young people want to be active participants in their care and involved in decisions about their treatment. However, there is a lack of digital shared decision-making tools available to support young people in child and adolescent mental health services (CAMHS). Objective The primary aim of this paper is to present the protocol of a feasibility trial for Power Up, a mobile phone app to empower young people in CAMHS to make their voices heard and participate in decisions around their care. Methods In the development phase, 30 young people, parents, and clinicians will take part in interviews and focus groups to elicit opinions on an early version of the app. In the feasibility testing phase, 60 young people from across 7 to 10 London CAMHS sites will take part in a trial looking at the feasibility and acceptability of measuring the impact of Power Up on shared decision making. Results Data collection for the development phase ended in December 2016. Data collection for the feasibility testing phase will end in December 2017. Conclusions Findings will inform the planning of a cluster controlled trial and contribute to the development and implementation of a shared decision-making app to be integrated into CAMHS. Trial Registration ISRCTN77194423; http://www.isrctn.com/ISRCTN77194423 (Archived by WebCite at http://www.webcitation.org/6td6MINP0). ClinicalTrials.gov NCT02987608; https://clinicaltrials.gov/ct2/show/NCT02987608 (Archived by WebCite at http://www.webcitation.org/6td6PNBZM) PMID:29084708
A workflow for reproducing mean benthic gas fluxes
NASA Astrophysics Data System (ADS)
Fulweiler, Robinson W.; Emery, Hollie E.; Maguire, Timothy J.
2016-08-01
Long-term data sets provide unique opportunities to examine temporal variability of key ecosystem processes. The need for such data sets is becoming increasingly important as we try to quantify the impact of human activities across various scales and in some cases, as we try to determine the success of management interventions. Unfortunately, long-term benthic flux data sets for coastal ecosystems are rare and curating them is a challenge. If we wish to make our data available to others now and into the future, however, then we need to provide mechanisms that allow others to understand our methods, access the data, reproduce the results, and see updates as they become available. Here we use techniques, learned through the EarthCube Ontosoft Geoscience Paper of the Future project, to develop best practices to allow us to share a long-term data set of directly measured net sediment N2 fluxes and sediment oxygen demand at two sites in Narragansett Bay, Rhode Island (USA). This technical report describes the process we used, the challenges we faced, and the steps we will take in the future to ensure transparency and reproducibility. By developing these data and software sharing tools we hope to help disseminate well-curated data with provenance as well as products from these data, so that the community can better assess how this temperate estuary has changed over time. We also hope to provide a data sharing model for others to follow so that long-term estuarine data are more easily shared and not lost over time.