Collaborative Initiative on Fetal Alcohol Spectrum Disorders: Methodology of Clinical Projects

PubMed Central

Mattson, Sarah N.; Foroud, Tatiana; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Coles, Claire D.; Fagerlund, Åse; Autti-Rämö, Ilona; May, Philip A.; Adnams, Colleen M.; Konovalova, Valentina; Wetherill, Leah; Arenson, Andrew D.; Barnett, William K.; Riley, Edward P.

2009-01-01

The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) was created in 2003 to further understanding of fetal alcohol spectrum disorders. Clinical and basic science projects collect data across multiple sites using standardized methodology. This paper describes the methodology being used by the clinical projects that pertain to assessment of children and adolescents. Domains being addressed are dysmorphology, neurobehavior, 3D facial imaging, and brain imaging. PMID:20036488

Development of Alternating Current Potential Drop (ACPD) Procedures for Crack Detection in Aluminum Aircraft Panels.

DOT National Transportation Integrated Search

1993-12-01

The Alternating Current Potential Drop (ACPD) method is investigated as a means of making measurements in laboratory experiments on the initiation and growth of multiple site damage (MSD) cracks in a common aluminum alloy used for aircraft constructi...

The Road to Tomorrow's Teachers: Planning, Implementing, and Evaluating a State-Based Special Education Workforce Development Initiative. Lessons Learned from the National Pilot Sites Project for Recruitment and Retention. Developing the Special Education Workforce.

ERIC Educational Resources Information Center

National Clearinghouse for Professions in Special Education, Arlington, VA.

This document describes the National Pilot Sites Project for Recruitment and Retention, an effort to recruit, prepare, and retain highly qualified diverse educators and related services personnel for children and youth with disabilities by involving multiple stakeholder groups within selected states (Alabama, Colorado, Georgia, New Jersey, Oregon,…

An unexpected phosphate binding site in Glyceraldehyde 3-Phosphate Dehydrogenase: Crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme

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

Cook, William J; Senkovich, Olga; Chattopadhyay, Debasish

2009-06-08

The structure, function and reaction mechanism of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) have been extensively studied. Based on these studies, three anion binding sites have been identified, one 'Ps' site (for binding the C-3 phosphate of the substrate) and two sites, 'Pi' and 'new Pi', for inorganic phosphate. According to the original flip-flop model, the substrate phosphate group switches from the 'Pi' to the 'Ps' site during the multistep reaction. In light of the discovery of the 'new Pi' site, a modified flip-flop mechanism, in which the C-3 phosphate of the substrate binds to the 'new Pi' site and flips tomore » the 'Ps' site before the hydride transfer, was proposed. An alternative model based on a number of structures of B. stearothermophilus GAPDH ternary complexes (non-covalent and thioacyl intermediate) proposes that in the ternary Michaelis complex the C-3 phosphate binds to the 'Ps' site and flips from the 'Ps' to the 'new Pi' site during or after the redox step. We determined the crystal structure of Cryptosporidium parvum GAPDH in the apo and holo (enzyme + NAD) state and the structure of the ternary enzyme-cofactor-substrate complex using an active site mutant enzyme. The C. parvum GAPDH complex was prepared by pre-incubating the enzyme with substrate and cofactor, thereby allowing free movement of the protein structure and substrate molecules during their initial encounter. Sulfate and phosphate ions were excluded from purification and crystallization steps. The quality of the electron density map at 2{angstrom} resolution allowed unambiguous positioning of the substrate. In three subunits of the homotetramer the C-3 phosphate group of the non-covalently bound substrate is in the 'new Pi' site. A concomitant movement of the phosphate binding loop is observed in these three subunits. In the fourth subunit the C-3 phosphate occupies an unexpected site not seen before and the phosphate binding loop remains in the substrate-free conformation. Orientation of the substrate with respect to the active site histidine and serine (in the mutant enzyme) also varies in different subunits. The structures of the C. parvum GAPDH ternary complex and other GAPDH complexes demonstrate the plasticity of the substrate binding site. We propose that the active site of GAPDH can accommodate the substrate in multiple conformations at multiple locations during the initial encounter. However, the C-3 phosphate group clearly prefers the 'new Pi' site for initial binding in the active site.« less

A probabilistic fatigue analysis of multiple site damage

NASA Technical Reports Server (NTRS)

Rohrbaugh, S. M.; Ruff, D.; Hillberry, B. M.; Mccabe, G.; Grandt, A. F., Jr.

1994-01-01

The variability in initial crack size and fatigue crack growth is incorporated in a probabilistic model that is used to predict the fatigue lives for unstiffened aluminum alloy panels containing multiple site damage (MSD). The uncertainty of the damage in the MSD panel is represented by a distribution of fatigue crack lengths that are analytically derived from equivalent initial flaw sizes. The variability in fatigue crack growth rate is characterized by stochastic descriptions of crack growth parameters for a modified Paris crack growth law. A Monte-Carlo simulation explicitly describes the MSD panel by randomly selecting values from the stochastic variables and then grows the MSD cracks with a deterministic fatigue model until the panel fails. Different simulations investigate the influences of the fatigue variability on the distributions of remaining fatigue lives. Six cases that consider fixed and variable conditions of initial crack size and fatigue crack growth rate are examined. The crack size distribution exhibited a dominant effect on the remaining fatigue life distribution, and the variable crack growth rate exhibited a lesser effect on the distribution. In addition, the probabilistic model predicted that only a small percentage of the life remains after a lead crack develops in the MSD panel.

Eruption of a Multiple-Turn Helical Magnetic Flux Tube in a Large Flare: Evidence for External and Internal Reconnection that Fits the Breakout Model of Solar Magnetic Eruptions

NASA Technical Reports Server (NTRS)

Gary, G. Allen; Moore, R. L.

2003-01-01

We present observations and an interpretation of a unique multiple-turn spiral flux tube eruption from AR10030 on 2002 July 15. The TRACE CIV observations clearly show a flux tube that is helical and that is erupting from within a sheared magnetic field. These observations are interpreted in the context of the breakout model for magnetic field explosions. The initiation of the helix eruption starts 25 seconds after the peak of the flare s strongest impulsive spike of microwave gryosynchrotron radiation early in the flare s explosive phase, implying that the sheared core field is not the site of the initial reconnection. Within the quadrupolar configuration of the active region, the external and internal reconnection sites are identified in each of two consecutive eruptive flares that produce a double CME. The first external breakout reconnection apparently releases an underlying sheared core field and allows it to erupt, leading to internal reconnection in the wake of the erupting helix. This internal reconnection heats the two-ribbon flare and might or might not produce the helix. These events lead to the first CME and are followed by a second breakout that initiates a second and larger halo CME. The strong magnetic shear in the region is associated with rapid proper motion and evolution of the active region. The multiple-turn helix originates from above a sheared-field magnetic inversion line within a filament channel, and starts to erupt only after fast breakout reconnection has started. These observations are counter to the standard flare model and support the breakout model for eruptive flare initiation. However, the observations are compatible with internal reconnection in a sheared magnetic arcade in the formation and eruption of the helix.

Eruption of a Multiple-Turn Helical Magnetic Flux Tube in a Large Flare: Evidence for External and Internal Reconnection that Fits the Breakout Model of Solar Magnetic Eruptions

NASA Technical Reports Server (NTRS)

Gary, G. Allen; Moore, R. L.

2004-01-01

We present observations and an interpretation of a unique multiple-turn spiral flux tube eruption from active region 10030 on 2002 July 15. The TRACE C IV observations clearly show a flux tube that is helical and erupting from within a sheared magnetic field. These observations are interpreted in the context of the breakout model for magnetic field explosions. The initiation of the helix eruption. as determined by a linear backward extrapolation, starts 25 s after the peak of the flare's strongest impulsive spike of microwave gyrosynchrotron radiation early in the flare s explosive phase, implying that the sheared core field is not the site of the initial reconnection. Within the quadrupolar configuration of the active region, the external and internal reconnection sites are identified in each of two consecutive eruptive flares that produce a double coronal mass ejection (CME). The first external breakout reconnection apparently releases an underlying sheared core field and allows it to erupt, leading to internal reconnection in the wake of the erupting helix. This internal reconnection releases the helix and heats the two-ribbon flare. These events lead to the first CME and are followed by a second breakout that initiates a second and larger halo CME. The strong magnetic shear in the region is compatible with the observed rapid proper motion and evolution of the active region. The multiple-turn helix originates from above a sheared-field magnetic inversion line within a filament channel. and starts to erupt only after fast breakout reconnection has started. These observations are counter to the standard flare model and support the breakout model for eruptive flare initiation.

Specialized nucleoprotein structures at the origin of replication of bacteriophage lambda: localized unwinding of duplex DNA by a six-protein reaction.

PubMed Central

Dodson, M; Echols, H; Wickner, S; Alfano, C; Mensa-Wilmot, K; Gomes, B; LeBowitz, J; Roberts, J D; McMacken, R

1986-01-01

The O protein of bacteriophage lambda localizes the initiation of DNA replication to a unique site on the lambda genome, ori lambda. By means of electron microscopy, we infer that the binding of O to ori lambda initiates a series of protein addition and transfer reactions that culminate in localized unwinding of the origin DNA, generating a prepriming structure for the initiation of DNA replication. We can define three stages of this prepriming reaction, the first two of which we have characterized previously. First, dimeric O protein binds to multiple DNA binding sites and self-associates to form a nucleoprotein structure, the O-some. Second, lambda P and host DnaB proteins interact with the O-some to generate a larger complex that includes additional DNA from an A + T-rich region adjacent to the O binding sites. Third, the addition of the DnaJ, DnaK, and Ssb proteins and ATP results in an origin-specific unwinding reaction, probably catalyzed by the helicase activity of DnaB. The unwinding reaction is unidirectional, proceeding "rightward" from the origin. The minimal DNA sequence competent for unwinding consists of two O binding sites and the adjacent A + T-rich region to the right of the binding sites. We conclude that the lambda O protein localizes and initiates a six-protein sequential reaction responsible for but preceding the precise initiation of DNA replication. Specialized nucleoprotein structures similar to the O-some may be a general feature of DNA transactions requiring extraordinary precision in localization and control. Images PMID:3020552

SPIDERS Bi-Directional Charging Station Interconnection Testing

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

Simpson, M.

2013-09-01

The Smart Power Infrastructure Demonstration for Energy Reliability and Security (SPIDERS) program is a multi-year Department of Defense-Department of Energy (DOE) collaborative effort that will demonstrate integration of renewables into island-able microgrids using on-site generation control, demand response, and energy storage with robust security features at multiple installations. Fort Carson, Colorado, will be the initial development and demonstration site for use of plug-in electric vehicles as energy storage (also known as vehicle-to-grid or V2G).

Service-Learning from a Distance: Partnering Multiple Universities and Local Governments in a Large Scale Initiative

ERIC Educational Resources Information Center

Poindexter, Sandra; Arnold, Pamela; Osterhout, Christopher

2009-01-01

Service-learning can be academically effective even when the distances between students and client organizations prevent face-to-face interchanges and site visits. Working with the State of Michigan and Michigan Townships Association, Michigan students from five universities learned about local government while helping Michigan townships develop…

Teacher Research in South Korean Early Childhood Education: New Initiative as Professional Development

ERIC Educational Resources Information Center

Kim, Mina; Kang, Bokyung

2012-01-01

This study was designed to explore how Korean preschool and kindergarten teachers understand teacher research and utilize it in professional development. Two teachers, two site directors, and one district supervisor were interviewed in South Korea. Data were collected in multiple ways: (1) open-ended individual interviews; (2) participants'…

Outplanting technique, host genotype, and site affect the initial success of outplanted Acropora cervicornis

PubMed Central

Gilliam, David S.

2018-01-01

Acropora cervicornis is the most widely used coral species for reef restoration in the greater Caribbean. However, outplanting methodologies (e.g., colony density, size, host genotype, and attachment technique) vary greatly, and to date have not been evaluated for optimality across multiple sites. Two experiments were completed during this study, the first evaluated the effects of attachment technique, colony size, and genotype by outplanting 405 A. cervicornis colonies, from ten genotypes, four size classes, and three attachment techniques (epoxy, nail and cable tie, or puck) across three sites. Colony survival, health condition, tissue productivity, and growth were assessed across one year for this experiment. The second experiment assessed the effect of colony density by outplanting colonies in plots of one, four, or 25 corals per 4 m2 across four separate sites. Plot survival and condition were evaluated across two years for this experiment in order to better capture the effect of increasing cover. Colonies attached with a nail and cable tie resulted in the highest survival regardless of colony size. Small corals had the lowest survival, but the greatest productivity. The majority of colony loss was attributed to missing colonies and was highest for pucks and small epoxied colonies. Disease and predation were observed at all sites, but did not affect all genotypes, however due to the overall low prevalence of either condition there were no significant differences found in any comparison. Low density plots had significantly higher survival and significantly lower prevalence of disease, predation, and missing colonies than high density plots. These results indicate that to increase initial outplant success, colonies of many genotypes should be outplanted to multiple sites using a nail and cable tie, in low densities, and with colonies over 15 cm total linear extension. PMID:29507829

Implementation of Policy, Systems, and Environmental Community-Based Interventions for Cardiovascular Health Through a National Not-for-Profit: A Multiple Case Study.

PubMed

Garney, Whitney R; Szucs, Leigh E; Primm, Kristin; King Hahn, Laura; Garcia, Kristen M; Martin, Emily; McLeroy, Kenneth

2018-05-01

In 2014, the Centers for Disease Control and Prevention funded the American Heart Association to implement policy, systems, and environment-focused strategies targeting access to healthy food and beverages, physical activity, and smoke-free environments. To understand factors affecting implementation and variations in success across sites, evaluators conducted a multiple case study. Based on past literature, community sites were categorized as capacity-building or implementation-ready, for comparison. A sample of six communities were selected using a systematic selection tool. Through site visits, evaluators conducted interviews with program staff and community partners and assessed action plans. Evaluators identified important implications for nationally coordinated community-based prevention programming. Differences in implementation varied by the communities' readiness, with the most notable differences in how they planned activities and defined success. Existing partner relationships (or lack thereof) played a significant role, regardless of the American Heart Association's existing presence within the communities, in the progression of initiatives and the differences observed among phases. Last, goals in capacity-building sites were tied to organizational goals while goals in implementation-ready sites were more incremental with increased community influence and buy-in. Using national organizations as a mechanism to carry out large-scale community-based prevention work is a viable option that provides coordinated, wide-scale implementation without sacrificing a community's priorities or input. In funding future initiatives, the presence of relationships and the time needed to cultivate such relationships should be accounted for in the planning and implementation processes, as well as both local and national expectations.

Biodegradation of Volatile Organic Compounds and Their Effects on Biodegradability under Co-Existing Conditions.

PubMed

Yoshikawa, Miho; Zhang, Ming; Toyota, Koki

2017-09-27

Volatile organic compounds (VOCs) are major pollutants that are found in contaminated sites, particularly in developed countries such as Japan. Various microorganisms that degrade individual VOCs have been reported, and genomic information related to their phylogenetic classification and VOC-degrading enzymes is available. However, the biodegradation of multiple VOCs remains a challenging issue. Practical sites, such as chemical factories, research facilities, and illegal dumping sites, are often contaminated with multiple VOCs. In order to investigate the potential of biodegrading multiple VOCs, we initially reviewed the biodegradation of individual VOCs. VOCs include chlorinated ethenes (tetrachloroethene, trichloroethene, dichloroethene, and vinyl chloride), BTEX (benzene, toluene, ethylbenzene, and xylene), and chlorinated methanes (carbon tetrachloride, chloroform, and dichloromethane). We also summarized essential information on the biodegradation of each kind of VOC under aerobic and anaerobic conditions, together with the microorganisms that are involved in VOC-degrading pathways. Interactions among multiple VOCs were then discussed based on concrete examples. Under conditions in which multiple VOCs co-exist, the biodegradation of a VOC may be constrained, enhanced, and/or unaffected by other compounds. Co-metabolism may enhance the degradation of other VOCs. In contrast, constraints are imposed by the toxicity of co-existing VOCs and their by-products, catabolite repression, or competition between VOC-degrading enzymes. This review provides fundamental, but systematic information for designing strategies for the bioremediation of multiple VOCs, as well as information on the role of key microorganisms that degrade VOCs.

Biodegradation of Volatile Organic Compounds and Their Effects on Biodegradability under Co-Existing Conditions

PubMed Central

Yoshikawa, Miho; Zhang, Ming; Toyota, Koki

2017-01-01

Volatile organic compounds (VOCs) are major pollutants that are found in contaminated sites, particularly in developed countries such as Japan. Various microorganisms that degrade individual VOCs have been reported, and genomic information related to their phylogenetic classification and VOC-degrading enzymes is available. However, the biodegradation of multiple VOCs remains a challenging issue. Practical sites, such as chemical factories, research facilities, and illegal dumping sites, are often contaminated with multiple VOCs. In order to investigate the potential of biodegrading multiple VOCs, we initially reviewed the biodegradation of individual VOCs. VOCs include chlorinated ethenes (tetrachloroethene, trichloroethene, dichloroethene, and vinyl chloride), BTEX (benzene, toluene, ethylbenzene, and xylene), and chlorinated methanes (carbon tetrachloride, chloroform, and dichloromethane). We also summarized essential information on the biodegradation of each kind of VOC under aerobic and anaerobic conditions, together with the microorganisms that are involved in VOC-degrading pathways. Interactions among multiple VOCs were then discussed based on concrete examples. Under conditions in which multiple VOCs co-exist, the biodegradation of a VOC may be constrained, enhanced, and/or unaffected by other compounds. Co-metabolism may enhance the degradation of other VOCs. In contrast, constraints are imposed by the toxicity of co-existing VOCs and their by-products, catabolite repression, or competition between VOC-degrading enzymes. This review provides fundamental, but systematic information for designing strategies for the bioremediation of multiple VOCs, as well as information on the role of key microorganisms that degrade VOCs. PMID:28904262

Polymer-Based Protein Engineering: Synthesis and Characterization of Armored, High Graft Density Polymer-Protein Conjugates.

PubMed

Carmali, Sheiliza; Murata, Hironobu; Cummings, Chad; Matyjaszewski, Krzysztof; Russell, Alan J

2017-01-01

Atom transfer radical polymerization (ATRP) from the surface of a protein can generate remarkably dense polymer shells that serve as armor and rationally tune protein function. Using straightforward chemistry, it is possible to covalently couple or display multiple small molecule initiators onto a protein surface. The chemistry is fine-tuned to be sequence specific (if one desires a single targeted site) at controlled density. Once the initiator is anchored on the protein surface, ATRP is used to grow polymers on protein surface, in situ. The technique is so powerful that a single-protein polymer conjugate molecule can contain more than 90% polymer coating by weight. If desired, stimuli-responsive polymers can be "grown" from the initiated sites to prepare enzyme conjugates that respond to external triggers such as temperature or pH, while still maintaining enzyme activity and stability. Herein, we focus mainly on the synthesis of chymotrypsin-polymer conjugates. Control of the number of covalently coupled initiator sites by changing the stoichiometric ratio between enzyme and the initiator during the synthesis of protein-initiator complexes allowed fine-tuning of the grafting density. For example, very high grafting density chymotrypsin conjugates were prepared from protein-initiator complexes to grow the temperature-responsive polymers, poly(N-isopropylacrylamide), and poly[N,N'-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate]. Controlled growth of polymers from protein surfaces enables one to predictably manipulate enzyme kinetics and stability without the need for molecular biology-dependent mutagenesis. © 2017 Elsevier Inc. All rights reserved.

Modeling Classical Swine Fever Outbreak-Related Outcomes

PubMed Central

Yadav, Shankar; Olynk Widmar, Nicole J.; Weng, Hsin-Yi

2016-01-01

The study was carried out to estimate classical swine fever (CSF) outbreak-related outcomes, such as epidemic duration and number of infected, vaccinated, and depopulated premises, using defined most likely CSF outbreak scenarios. Risk metrics were established using empirical data to select the most likely CSF outbreak scenarios in Indiana. These scenarios were simulated using a stochastic between-premises disease spread model to estimate outbreak-related outcomes. A total of 19 single-site (i.e., with one index premises at the onset of an outbreak) and 15 multiple-site (i.e., with more than one index premises at the onset of an outbreak) outbreak scenarios of CSF were selected using the risk metrics. The number of index premises in the multiple-site outbreak scenarios ranged from 4 to 32. The multiple-site outbreak scenarios were further classified into clustered (N = 6) and non-clustered (N = 9) groups. The estimated median (5th, 95th percentiles) epidemic duration (days) was 224 (24, 343) in the single-site and was 190 (157, 251) and 210 (167, 302) in the clustered and non-clustered multiple-site outbreak scenarios, respectively. The median (5th, 95th percentiles) number of infected premises was 323 (0, 488) in the single-site outbreak scenarios and was 529 (395, 662) and 465 (295, 640) in the clustered and non-clustered multiple-site outbreak scenarios, respectively. Both the number and spatial distributions of the index premises affected the outcome estimates. The results also showed the importance of implementing vaccinations to accommodate depopulation in the CSF outbreak controls. The use of routinely collected surveillance data in the risk metrics and disease spread model allows end users to generate timely outbreak-related information based on the initial outbreak’s characteristics. Swine producers can use this information to make an informed decision on the management of swine operations and continuity of business, so that potential losses could be minimized during a CSF outbreak. Government authorities might use the information to make emergency preparedness plans for CSF outbreak control. PMID:26870741

Decomposition and nitrogen dynamics of 15N-labeled leaf, root, and twig litter in temperate coniferous forests

USGS Publications Warehouse

van Huysen, Tiff L.; Harmon, Mark E.; Perakis, Steven S.; Chen, Hua

2013-01-01

Litter nutrient dynamics contribute significantly to biogeochemical cycling in forest ecosystems. We examined how site environment and initial substrate quality influence decomposition and nitrogen (N) dynamics of multiple litter types. A 2.5-year decomposition study was installed in the Oregon Coast Range and West Cascades using 15N-labeled litter from Acer macrophyllum, Picea sitchensis, and Pseudotsuga menziesii. Mass loss for leaf litter was similar between the two sites, while root and twig litter exhibited greater mass loss in the Coast Range. Mass loss was greatest from leaves and roots, and species differences in mass loss were more prominent in the Coast Range. All litter types and species mineralized N early in the decomposition process; only A. macrophyllum leaves exhibited a net N immobilization phase. There were no site differences with respect to litter N dynamics despite differences in site N availability, and litter N mineralization patterns were species-specific. For multiple litter × species combinations, the difference between gross and net N mineralization was significant, and gross mineralization was 7–20 % greater than net mineralization. The mineralization results suggest that initial litter chemistry may be an important driver of litter N dynamics. Our study demonstrates that greater amounts of N are cycling through these systems than may be quantified by only measuring net mineralization and challenges current leaf-based biogeochemical theory regarding patterns of N immobilization and mineralization.

DC-Analyzer-facilitated combinatorial strategy for rapid directed evolution of functional enzymes with multiple mutagenesis sites.

PubMed

Wang, Xiong; Zheng, Kai; Zheng, Huayu; Nie, Hongli; Yang, Zujun; Tang, Lixia

2014-12-20

Iterative saturation mutagenesis (ISM) has been shown to be a powerful method for directed evolution. In this study, the approach was modified (termed M-ISM) by combining the single-site saturation mutagenesis method with a DC-Analyzer-facilitated combinatorial strategy, aiming to evolve novel biocatalysts efficiently in the case where multiple sites are targeted simultaneously. Initially, all target sites were explored individually by constructing single-site saturation mutagenesis libraries. Next, the top two to four variants in each library were selected and combined using the DC-Analyzer-facilitated combinatorial strategy. In addition to site-saturation mutagenesis, iterative saturation mutagenesis also needed to be performed. The advantages of M-ISM over ISM were that the screening effort is greatly reduced, and the entire M-ISM procedure was less time-consuming. The M-ISM strategy was successfully applied to the randomization of halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) when five interesting sites were targeted simultaneously. After screening 900 clones in total, six positive mutants were obtained. These mutants exhibited 4.0- to 9.3-fold higher k(cat) values than did the wild-type HheC toward 1,3-dichloro-2-propanol. However, with the ISM strategy, the best hit showed a 5.9-fold higher k(cat) value toward 1,3-DCP than the wild-type HheC, which was obtained after screening 4000 clones from four rounds of mutagenesis. Therefore, M-ISM could serve as a simple and efficient version of ISM for the randomization of target genes with multiple positions of interest.

BOREAS RSS-8 BIOME-BGC Model Simulations at Tower Flux Sites in 1994

NASA Technical Reports Server (NTRS)

Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Kimball, John

2000-01-01

BIOME-BGC is a general ecosystem process model designed to simulate biogeochemical and hydrologic processes across multiple scales (Running and Hunt, 1993). In this investigation, BIOME-BGC was used to estimate daily water and carbon budgets for the BOREAS tower flux sites for 1994. Carbon variables estimated by the model include gross primary production (i.e., net photosynthesis), maintenance and heterotrophic respiration, net primary production, and net ecosystem carbon exchange. Hydrologic variables estimated by the model include snowcover, evaporation, transpiration, evapotranspiration, soil moisture, and outflow. The information provided by the investigation includes input initialization and model output files for various sites in tabular ASCII format.

Tetramerization and interdomain flexibility of the replication initiation controller YabA enables simultaneous binding to multiple partners

PubMed Central

Felicori, Liza; Jameson, Katie H.; Roblin, Pierre; Fogg, Mark J.; Garcia-Garcia, Transito; Ventroux, Magali; Cherrier, Mickaël V.; Bazin, Alexandre; Noirot, Philippe; Wilkinson, Anthony J.; Molina, Franck; Terradot, Laurent; Noirot-Gros, Marie-Françoise

2016-01-01

YabA negatively regulates initiation of DNA replication in low-GC Gram-positive bacteria. The protein exerts its control through interactions with the initiator protein DnaA and the sliding clamp DnaN. Here, we combined X-ray crystallography, X-ray scattering (SAXS), modeling and biophysical approaches, with in vivo experimental data to gain insight into YabA function. The crystal structure of the N-terminal domain (NTD) of YabA solved at 2.7 Å resolution reveals an extended α-helix that contributes to an intermolecular four-helix bundle. Homology modeling and biochemical analysis indicates that the C-terminal domain (CTD) of YabA is a small Zn-binding domain. Multi-angle light scattering and SAXS demonstrate that YabA is a tetramer in which the CTDs are independent and connected to the N-terminal four-helix bundle via flexible linkers. While YabA can simultaneously interact with both DnaA and DnaN, we found that an isolated CTD can bind to either DnaA or DnaN, individually. Site-directed mutagenesis and yeast-two hybrid assays identified DnaA and DnaN binding sites on the YabA CTD that partially overlap and point to a mutually exclusive mode of interaction. Our study defines YabA as a novel structural hub and explains how the protein tetramer uses independent CTDs to bind multiple partners to orchestrate replication initiation in the bacterial cell. PMID:26615189

Size of Ovulatory Follicles in Cattle Expressing Multiple Ovulations Naturally and Its Influence on Corpus Luteum Development and Fertility

USDA-ARS?s Scientific Manuscript database

Long-term genetic selection of cattle for fraternal twins has increased the frequency of twin and triplet ovulations. Although twin and triplet ovulations increased pregnancy rates initially, ratio of fetal number:ovulation site in pregnant females with twin (0.83) or triplet (0.73) ovulations was <...

Decomposition and nitrogen dynamics of 15N-labeled leaf, root, and twig litter in temperate coniferous forests

Treesearch

T.L. van Huysen; M.E. Harmon; S.S. Perakis; H. Chen

2013-01-01

Litter nutrient dynamics contribute significantly to biogeochemical cycling in forest ecosystems. We examined how site environment and initial substrate quality influence decomposition and nitrogen (N) dynamics of multiple litter types. A 2.5-year decomposition study was installed in the Oregon Coast Range and West Cascades using 15N-labeled...

Identification and characterization of ARS-like sequences as putative origin(s) of replication in human malaria parasite Plasmodium falciparum.

PubMed

Agarwal, Meetu; Bhowmick, Krishanu; Shah, Kushal; Krishnamachari, Annangarachari; Dhar, Suman Kumar

2017-08-01

DNA replication is a fundamental process in genome maintenance, and initiates from several genomic sites (origins) in eukaryotes. In Saccharomyces cerevisiae, conserved sequences known as autonomously replicating sequences (ARSs) provide a landing pad for the origin recognition complex (ORC), leading to replication initiation. Although origins from higher eukaryotes share some common sequence features, the definitive genomic organization of these sites remains elusive. The human malaria parasite Plasmodium falciparum undergoes multiple rounds of DNA replication; therefore, control of initiation events is crucial to ensure proper replication. However, the sites of DNA replication initiation and the mechanism by which replication is initiated are poorly understood. Here, we have identified and characterized putative origins in P. falciparum by bioinformatics analyses and experimental approaches. An autocorrelation measure method was initially used to search for regions with marked fluctuation (dips) in the chromosome, which we hypothesized might contain potential origins. Indeed, S. cerevisiae ARS consensus sequences were found in dip regions. Several of these P. falciparum sequences were validated with chromatin immunoprecipitation-quantitative PCR, nascent strand abundance and a plasmid stability assay. Subsequently, the same sequences were used in yeast to confirm their potential as origins in vivo. Our results identify the presence of functional ARSs in P. falciparum and provide meaningful insights into replication origins in these deadly parasites. These data could be useful in designing transgenic vectors with improved stability for transfection in P. falciparum. © 2017 Federation of European Biochemical Societies.

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

PubMed

Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

2015-01-01

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Practical management of anticoagulation in patients with atrial fibrillation.

PubMed

Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

2015-04-07

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Rates and determinants of early initiation of breastfeeding and exclusive breast feeding at 42 days postnatal in six low and middle-income countries: A prospective cohort study

PubMed Central

2015-01-01

Background Early initiation of breastfeeding after birth and exclusive breastfeeding through six months of age confers many health benefits for infants; both are crucial high impact, low-cost interventions. However, determining accurate global rates of these crucial activities has been challenging. We use population-based data to describe: (1) rates of early initiation of breastfeeding (defined as within 1 hour of birth) and of exclusive breastfeeding at 42 days post-partum; and (2) factors associated with failure to initiate early breastfeeding and exclusive breastfeeding at 42 days post-partum. Methods Prospectively collected data from women and their live-born infants enrolled in the Global Network’s Maternal and Newborn Health Registry between January 1, 2010-December 31, 2013 included women-infant dyads in 106 geographic areas (clusters) at 7 research sites in 6 countries (Kenya, Zambia, India [2 sites], Pakistan, Argentina and Guatemala). Rates and risk factors for failure to initiate early breastfeeding were investigated for the entire cohort and rates and risk factors for failure to maintain exclusive breastfeeding was assessed in a sub-sample studied at 42 days post-partum. Result A total of 255,495 live-born women-infant dyads were included in the study. Rates and determinants for the exclusive breastfeeding sub-study at 42 days post-partum were assessed from among a sub-sample of 105,563 subjects. Although there was heterogeneity by site, and early initiation of breastfeeding after delivery was high, the Pakistan site had the lowest rates of early initiation of breastfeeding. The Pakistan site also had the highest rate of lack of exclusive breastfeeding at 42 days post-partum. Across all regions, factors associated with failure to initiate early breastfeeding included nulliparity, caesarean section, low birth weight, resuscitation with bag and mask, and failure to place baby on the mother’s chest after delivery. Factors associated with failure to achieve exclusive breastfeeding at 42 days varied across the sites. The only factor significant in all sites was multiple gestation. Conclusions In this large, prospective, population-based, observational study, rates of both early initiation of breastfeeding and exclusive breastfeeding at 42 days post-partum were high, except in Pakistan. Factors associated with these key breastfeeding indicators should assist with more effective strategies to scale-up these crucial public health interventions. Trial registration Registration at the Clinicaltrials.gov website (ID# NCT01073475). PMID:26063291

Rates and determinants of early initiation of breastfeeding and exclusive breast feeding at 42 days postnatal in six low and middle-income countries: A prospective cohort study.

PubMed

Patel, Archana; Bucher, Sherri; Pusdekar, Yamini; Esamai, Fabian; Krebs, Nancy F; Goudar, Shivaprasad S; Chomba, Elwyn; Garces, Ana; Pasha, Omrana; Saleem, Sarah; Kodkany, Bhalachandra S; Liechty, Edward A; Kodkany, Bhala; Derman, Richard J; Carlo, Waldemar A; Hambidge, K; Goldenberg, Robert L; Althabe, Fernando; Berrueta, Mabel; Moore, Janet L; McClure, Elizabeth M; Koso-Thomas, Marion; Hibberd, Patricia L

2015-01-01

Early initiation of breastfeeding after birth and exclusive breastfeeding through six months of age confers many health benefits for infants; both are crucial high impact, low-cost interventions. However, determining accurate global rates of these crucial activities has been challenging. We use population-based data to describe: (1) rates of early initiation of breastfeeding (defined as within 1 hour of birth) and of exclusive breastfeeding at 42 days post-partum; and (2) factors associated with failure to initiate early breastfeeding and exclusive breastfeeding at 42 days post-partum. Prospectively collected data from women and their live-born infants enrolled in the Global Network's Maternal and Newborn Health Registry between January 1, 2010-December 31, 2013 included women-infant dyads in 106 geographic areas (clusters) at 7 research sites in 6 countries (Kenya, Zambia, India [2 sites], Pakistan, Argentina and Guatemala). Rates and risk factors for failure to initiate early breastfeeding were investigated for the entire cohort and rates and risk factors for failure to maintain exclusive breastfeeding was assessed in a sub-sample studied at 42 days post-partum. A total of 255,495 live-born women-infant dyads were included in the study. Rates and determinants for the exclusive breastfeeding sub-study at 42 days post-partum were assessed from among a sub-sample of 105,563 subjects. Although there was heterogeneity by site, and early initiation of breastfeeding after delivery was high, the Pakistan site had the lowest rates of early initiation of breastfeeding. The Pakistan site also had the highest rate of lack of exclusive breastfeeding at 42 days post-partum. Across all regions, factors associated with failure to initiate early breastfeeding included nulliparity, caesarean section, low birth weight, resuscitation with bag and mask, and failure to place baby on the mother's chest after delivery. Factors associated with failure to achieve exclusive breastfeeding at 42 days varied across the sites. The only factor significant in all sites was multiple gestation. In this large, prospective, population-based, observational study, rates of both early initiation of breastfeeding and exclusive breastfeeding at 42 days post-partum were high, except in Pakistan. Factors associated with these key breastfeeding indicators should assist with more effective strategies to scale-up these crucial public health interventions. Registration at the Clinicaltrials.gov website (ID# NCT01073475).

Computational investigation of cholesterol binding sites on mitochondrial VDAC.

PubMed

Weiser, Brian P; Salari, Reza; Eckenhoff, Roderic G; Brannigan, Grace

2014-08-21

The mitochondrial voltage-dependent anion channel (VDAC) allows passage of ions and metabolites across the mitochondrial outer membrane. Cholesterol binds mammalian VDAC, and we investigated the effects of binding to human VDAC1 with atomistic molecular dynamics simulations that totaled 1.4 μs. We docked cholesterol to specific sites on VDAC that were previously identified with NMR, and we tested the reliability of multiple docking results in each site with simulations. The most favorable binding modes were used to build a VDAC model with cholesterol occupying five unique sites, and during multiple 100 ns simulations, cholesterol stably and reproducibly remained bound to the protein. For comparison, VDAC was simulated in systems with identical components but with cholesterol initially unbound. The dynamics of loops that connect adjacent β-strands were most affected by bound cholesterol, with the averaged root-mean-square fluctuation (RMSF) of multiple residues altered by 20-30%. Cholesterol binding also stabilized charged residues inside the channel and localized the surrounding electrostatic potentials. Despite this, ion diffusion through the channel was not significantly affected by bound cholesterol, as evidenced by multi-ion potential of mean force measurements. Although we observed modest effects of cholesterol on the open channel, our model will be particularly useful in experiments that investigate how cholesterol affects VDAC function under applied electrochemical forces and also how other ligands and proteins interact with the channel.

Computational Investigation of Cholesterol Binding Sites on Mitochondrial VDAC

PubMed Central

2015-01-01

The mitochondrial voltage-dependent anion channel (VDAC) allows passage of ions and metabolites across the mitochondrial outer membrane. Cholesterol binds mammalian VDAC, and we investigated the effects of binding to human VDAC1 with atomistic molecular dynamics simulations that totaled 1.4 μs. We docked cholesterol to specific sites on VDAC that were previously identified with NMR, and we tested the reliability of multiple docking results in each site with simulations. The most favorable binding modes were used to build a VDAC model with cholesterol occupying five unique sites, and during multiple 100 ns simulations, cholesterol stably and reproducibly remained bound to the protein. For comparison, VDAC was simulated in systems with identical components but with cholesterol initially unbound. The dynamics of loops that connect adjacent β-strands were most affected by bound cholesterol, with the averaged root-mean-square fluctuation (RMSF) of multiple residues altered by 20–30%. Cholesterol binding also stabilized charged residues inside the channel and localized the surrounding electrostatic potentials. Despite this, ion diffusion through the channel was not significantly affected by bound cholesterol, as evidenced by multi-ion potential of mean force measurements. Although we observed modest effects of cholesterol on the open channel, our model will be particularly useful in experiments that investigate how cholesterol affects VDAC function under applied electrochemical forces and also how other ligands and proteins interact with the channel. PMID:25080204

End of FY10 report - used fuel disposition technical bases and lessons learned : legal and regulatory framework for high-level waste disposition in the United States.

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

Weiner, Ruth F.; Blink, James A.; Rechard, Robert Paul

This report examines the current policy, legal, and regulatory framework pertaining to used nuclear fuel and high level waste management in the United States. The goal is to identify potential changes that if made could add flexibility and possibly improve the chances of successfully implementing technical aspects of a nuclear waste policy. Experience suggests that the regulatory framework should be established prior to initiating future repository development. Concerning specifics of the regulatory framework, reasonable expectation as the standard of proof was successfully implemented and could be retained in the future; yet, the current classification system for radioactive waste, including hazardousmore » constituents, warrants reexamination. Whether or not consideration of multiple sites are considered simultaneously in the future, inclusion of mechanisms such as deliberate use of performance assessment to manage site characterization would be wise. Because of experience gained here and abroad, diversity of geologic media is not particularly necessary as a criterion in site selection guidelines for multiple sites. Stepwise development of the repository program that includes flexibility also warrants serious consideration. Furthermore, integration of the waste management system from storage, transportation, and disposition, should be examined and would be facilitated by integration of the legal and regulatory framework. Finally, in order to enhance acceptability of future repository development, the national policy should be cognizant of those policy and technical attributes that enhance initial acceptance, and those policy and technical attributes that maintain and broaden credibility.« less

Intracranial meningeal hemangiopericytoma: Recurrences at the initial and distant intracranial sites and extraneural metastases to multiple organs

PubMed Central

WEI, GUANGQUAN; KANG, XIAOWEI; LIU, XIANPING; TANG, XING; LI, QINLONG; HAN, JUNTAO; YIN, HONG

2015-01-01

Regardless of the controversial pathogenesis, intracranial meningeal hemangiopericytoma (M-HPC) is a rare, highly cellular and vascularized mesenchymal tumor that is characterized by a high tendency for recurrence and extraneural metastasis, despite radical excision and postoperative radiotherapy. M-HPC shares similar clinical manifestations and radiological findings with meningioma, which causes difficulty in differentiation of this entity from those prognostically favorable mimics prior to surgery. Treatment of M-HPC, particularly in metastatic settings, remains a challenge. A case is described of primary M-HPC with recurrence at the initial and distant intracranial sites and extraneural multiple-organ metastases in a 36-year-old female. The metastasis of M-HPC was extremely extensive, and to the best of our knowledge this is the first case of M-HPC with delayed metastasis to the bilateral kidneys. The data suggests that preoperative computed tomography and magnetic resonance imaging could provide certain diagnostic clues and useful information for more optimal treatment planning. The results may imply that novel drugs, such as temozolomide and bevacizumab, as a component of multimodality therapy of M-HPC may deserve further investigation. PMID:26171177

The nature of the mineral component of bone and the mechanism of calcification.

PubMed

Glimcher, M J

1987-01-01

From the physical chemical standpoint, the formation of a solid phase of Ca-P in bone represents a phase transformation, a process exemplified by the formation of ice from water. Considering the structural complexity and abundance of highly organized macromolecules in the cells and extracellular tissue spaces of mineralized tissues generally and in bone particularly, it is inconceivable that this phase transformation occurs by homogeneous nucleation, i.e., without the active participation of an organic component acting as a nucleator. This is almost surely true in biologic mineralization in general. Electron micrographs and low-angle neutron and X-ray diffraction studies clearly show that calcification of collagen fibrils occurs in an extremely intimate and highly organized fashion: initiation of crystal formation within the collagen fibrils in the hole zone region, with the long axes (c-axis) of the crystals aligned roughly parallel to the long axis of the fibril within which they are located. Crystals are initially formed in hole zone regions within individual fibrils separated by unmineralized regions. Calcification is initiated in spatially distinct nucleation sites. This indicates that such regions within a single, undirectional fibril represents independent sites for heterogeneous nucleation. Clearly, sites where mineralization is initiated in adjacent collagen fibrils are even further separated, emphasizing even more clearly that the process of progressive calcification of the collagen fibrils and therefore of the tissue is characterized principally by the presence of increasing numbers of independent nucleation sites within additional hole zone regions of the collagen fibrils. The increase in the mass of Ca-P apatite accrues principally by multiplication of more crystals, mostly by secondary nucleation from the crystals initially deposited in the hole zone region. Very little additional growth of the crystals occurs with time, the additional increase in mineral mass being principally the result of increase in the number of crystals (multiplication), not size of the crystals (crystal growth). The crystals within the collagen fibers grow in number and possibly in size to extend into the overlap zone of the collagen fibrils ("pores") so that all of the available space within the fibrils, which has possibly expanded in volume from its uncalcified level, is eventually occupied by the mineral crystals. It must be recognized that the calcification of separate tissue components and compartments (collagen, mitochondria, matrix vesicles) must be an independent physical chemical event.(ABSTRACT TRUNCATED AT 400 WORDS)

Intrinsically bent DNA in replication origins and gene promoters.

PubMed

Gimenes, F; Takeda, K I; Fiorini, A; Gouveia, F S; Fernandez, M A

2008-06-24

Intrinsically bent DNA is an alternative conformation of the DNA molecule caused by the presence of dA/dT tracts, 2 to 6 bp long, in a helical turn phase DNA or with multiple intervals of 10 to 11 bp. Other than flexibility, intrinsic bending sites induce DNA curvature in particular chromosome regions such as replication origins and promoters. Intrinsically bent DNA sites are important in initiating DNA replication, and are sometimes found near to regions associated with the nuclear matrix. Many methods have been developed to localize bent sites, for example, circular permutation, computational analysis, and atomic force microscopy. This review discusses intrinsically bent DNA sites associated with replication origins and gene promoter regions in prokaryote and eukaryote cells. We also describe methods for identifying bent DNA sites for circular permutation and computational analysis.

U-PLANT GEOGRAPHIC ZONE CLEANUP PROTOTYPE

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

ROMINE, L.D.

2006-02-01

The U Plant geographic zone (UPZ) occupies 0.83 square kilometers on the Hanford Site Central Plateau (200 Area). It encompasses the U Plant canyon (221-U Facility), ancillary facilities that supported the canyon, soil waste sites, and underground pipelines. The UPZ cleanup initiative coordinates the cleanup of the major facilities, ancillary facilities, waste sites, and contaminated pipelines (collectively identified as ''cleanup items'') within the geographic zone. The UPZ was selected as a geographic cleanup zone prototype for resolving regulatory, technical, and stakeholder issues and demonstrating cleanup methods for several reasons: most of the area is inactive, sufficient characterization information is availablemore » to support decisions, cleanup of the high-risk waste sites will help protect the groundwater, and the zone contains a representative cross-section of the types of cleanup actions that will be required in other geographic zones. The UPZ cleanup demonstrates the first of 22 integrated zone cleanup actions on the Hanford Site Central Plateau to address threats to groundwater, the environment, and human health. The UPZ contains more than 100 individual cleanup items. Cleanup actions in the zone will be undertaken using multiple regulatory processes and decision documents. Cleanup actions will include building demolition, waste site and pipeline excavation, and the construction of multiple, large engineered barriers. In some cases, different cleanup actions may be taken at item locations that are immediately adjacent to each other. The cleanup planning and field activities for each cleanup item must be undertaken in a coordinated and cohesive manner to ensure effective execution of the UPZ cleanup initiative. The UPZ zone cleanup implementation plan (ZCIP) was developed to address the need for a fundamental integration tool for UPZ cleanup. As UPZ cleanup planning and implementation moves forward, the ZCIP is intended to be a living document that will provide a focal point for integrating UPZ actions, including field cleanup activities, waste staging and handling, and post-cleanup monitoring and institutional controls.« less

Structures of minute virus of mice replication initiator protein N-terminal domain: Insights into DNA nicking and origin binding

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

Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan

Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase activemore » site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication.« less

Protocol: Adaptive Implementation of Effective Programs Trial (ADEPT): cluster randomized SMART trial comparing a standard versus enhanced implementation strategy to improve outcomes of a mood disorders program.

PubMed

Kilbourne, Amy M; Almirall, Daniel; Eisenberg, Daniel; Waxmonsky, Jeanette; Goodrich, David E; Fortney, John C; Kirchner, JoAnn E; Solberg, Leif I; Main, Deborah; Bauer, Mark S; Kyle, Julia; Murphy, Susan A; Nord, Kristina M; Thomas, Marshall R

2014-09-30

Despite the availability of psychosocial evidence-based practices (EBPs), treatment and outcomes for persons with mental disorders remain suboptimal. Replicating Effective Programs (REP), an effective implementation strategy, still resulted in less than half of sites using an EBP. The primary aim of this cluster randomized trial is to determine, among sites not initially responding to REP, the effect of adaptive implementation strategies that begin with an External Facilitator (EF) or with an External Facilitator plus an Internal Facilitator (IF) on improved EBP use and patient outcomes in 12 months. This study employs a sequential multiple assignment randomized trial (SMART) design to build an adaptive implementation strategy. The EBP to be implemented is life goals (LG) for patients with mood disorders across 80 community-based outpatient clinics (N = 1,600 patients) from different U.S. regions. Sites not initially responding to REP (defined as < 50% patients receiving ≥ 3 EBP sessions) will be randomized to receive additional support from an EF or both EF/IF. Additionally, sites randomized to EF and still not responsive will be randomized to continue with EF alone or to receive EF/IF. The EF provides technical expertise in adapting LG in routine practice, whereas the on-site IF has direct reporting relationships to site leadership to support LG use in routine practice. The primary outcome is mental health-related quality of life; secondary outcomes include receipt of LG sessions, mood symptoms, implementation costs, and organizational change. This study design will determine whether an off-site EF alone versus the addition of an on-site IF improves EBP uptake and patient outcomes among sites that do not respond initially to REP. It will also examine the value of delaying the provision of EF/IF for sites that continue to not respond despite EF. ClinicalTrials.gov identifier: NCT02151331.

Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe.

PubMed

Marques, Catarina A; Dickens, Nicholas J; Paape, Daniel; Campbell, Samantha J; McCulloch, Richard

2015-10-19

DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania. Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins. The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture.

Molecular Characterization of Transgene Integration by Next-Generation Sequencing in Transgenic Cattle

PubMed Central

Zhang, Ran; Yin, Yinliang; Zhang, Yujun; Li, Kexin; Zhu, Hongxia; Gong, Qin; Wang, Jianwu; Hu, Xiaoxiang; Li, Ning

2012-01-01

As the number of transgenic livestock increases, reliable detection and molecular characterization of transgene integration sites and copy number are crucial not only for interpreting the relationship between the integration site and the specific phenotype but also for commercial and economic demands. However, the ability of conventional PCR techniques to detect incomplete and multiple integration events is limited, making it technically challenging to characterize transgenes. Next-generation sequencing has enabled cost-effective, routine and widespread high-throughput genomic analysis. Here, we demonstrate the use of next-generation sequencing to extensively characterize cattle harboring a 150-kb human lactoferrin transgene that was initially analyzed by chromosome walking without success. Using this approach, the sites upstream and downstream of the target gene integration site in the host genome were identified at the single nucleotide level. The sequencing result was verified by event-specific PCR for the integration sites and FISH for the chromosomal location. Sequencing depth analysis revealed that multiple copies of the incomplete target gene and the vector backbone were present in the host genome. Upon integration, complex recombination was also observed between the target gene and the vector backbone. These findings indicate that next-generation sequencing is a reliable and accurate approach for the molecular characterization of the transgene sequence, integration sites and copy number in transgenic species. PMID:23185606

Kirschenmann Road multi-well monitoring site, Cuyama Valley, Santa Barbara County, California

USGS Publications Warehouse

Everett, R.R.; Hanson, R.T.; Sweetkind, D.S.

2011-01-01

The U.S. Geological Survey (USGS), in cooperation with the Water Agency Division of the Santa Barbara County Department of Public Works, is evaluating the geohydrology and water availability of the Cuyama Valley, California (fig. 1). As part of this evaluation, the USGS installed the Cuyama Valley Kirschenmann Road multiple-well monitoring site (CVKR) in the South-Main subregion of the Cuyama Valley (fig. 1). The CVKR well site is designed to allow for the collection of depth-specific water-level and water-quality data. Data collected at this site provides information about the geology, hydrology, geophysics, and geochemistry of the local aquifer system, thus, enhancing the understanding of the geohydrologic framework of the Cuyama Valley. This report presents the construction information and initial geohydrologic data collected from the CVKR monitoring site, along with a brief comparison to selected supply and irrigation wells from the major subregions of the Cuyama Valley (fig. 1).

Chromatin-Specific Regulation of Mammalian rDNA Transcription by Clustered TTF-I Binding Sites

PubMed Central

Diermeier, Sarah D.; Németh, Attila; Rehli, Michael; Grummt, Ingrid; Längst, Gernot

2013-01-01

Enhancers and promoters often contain multiple binding sites for the same transcription factor, suggesting that homotypic clustering of binding sites may serve a role in transcription regulation. Here we show that clustering of binding sites for the transcription termination factor TTF-I downstream of the pre-rRNA coding region specifies transcription termination, increases the efficiency of transcription initiation and affects the three-dimensional structure of rRNA genes. On chromatin templates, but not on free rDNA, clustered binding sites promote cooperative binding of TTF-I, loading TTF-I to the downstream terminators before it binds to the rDNA promoter. Interaction of TTF-I with target sites upstream and downstream of the rDNA transcription unit connects these distal DNA elements by forming a chromatin loop between the rDNA promoter and the terminators. The results imply that clustered binding sites increase the binding affinity of transcription factors in chromatin, thus influencing the timing and strength of DNA-dependent processes. PMID:24068958

Nucleation of shear bands in amorphous alloys

PubMed Central

Perepezko, John H.; Imhoff, Seth D.; Chen, Ming-Wei; Wang, Jun-Qiang; Gonzalez, Sergio

2014-01-01

The initiation and propagation of shear bands is an important mode of localized inhomogeneous deformation that occurs in a wide range of materials. In metallic glasses, shear band development is considered to center on a structural heterogeneity, a shear transformation zone that evolves into a rapidly propagating shear band under a shear stress above a threshold. Deformation by shear bands is a nucleation-controlled process, but the initiation process is unclear. Here we use nanoindentation to probe shear band nucleation during loading by measuring the first pop-in event in the load–depth curve which is demonstrated to be associated with shear band formation. We analyze a large number of independent measurements on four different bulk metallic glasses (BMGs) alloys and reveal the operation of a bimodal distribution of the first pop-in loads that are associated with different shear band nucleation sites that operate at different stress levels below the glass transition temperature, Tg. The nucleation kinetics, the nucleation barriers, and the density for each site type have been determined. The discovery of multiple shear band nucleation sites challenges the current view of nucleation at a single type of site and offers opportunities for controlling the ductility of BMG alloys. PMID:24594599

A sensitive mass spectrometric method for hypothesis-driven detection of peptide post-translational modifications: multiple reaction monitoring-initiated detection and sequencing (MIDAS).

PubMed

Unwin, Richard D; Griffiths, John R; Whetton, Anthony D

2009-01-01

The application of a targeted mass spectrometric workflow to the sensitive identification of post-translational modifications is described. This protocol employs multiple reaction monitoring (MRM) to search for all putative peptides specifically modified in a target protein. Positive MRMs trigger an MS/MS experiment to confirm the nature and site of the modification. This approach, termed MIDAS (MRM-initiated detection and sequencing), is more sensitive than approaches using neutral loss scanning or precursor ion scanning methodologies, due to a more efficient use of duty cycle along with a decreased background signal associated with MRM. We describe the use of MIDAS for the identification of phosphorylation, with a typical experiment taking just a couple of hours from obtaining a peptide sample. With minor modifications, the MIDAS method can be applied to other protein modifications or unmodified peptides can be used as a MIDAS target.

Evaluation of Three Sites for the Global Nuclear Energy Partnership

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

Magette, T.E.; Turner, S.; Smalley, R.

The Global Nuclear Energy Partnership (GNEP) is an initiative managed by the United States Department of Energy (DOE) to work with other nations to develop and deploy advanced nuclear recycling and reactor technologies. The purpose of this initiative is to help provide reliable, emission-free energy with less waste burden of older technologies and without making available separated plutonium that could be used by rogue states or terrorists for nuclear weapons. In November 2006, DOE awarded multiple contracts to EnergySolutions to prepare separate siting studies to determine the possibility of hosting a Consolidated Fuel Treatment Center (CFTC) and/or an Advanced Burnermore » Reactor (ABR) at three proposed sites: The Atomic City Site in Bingham County, Idaho; the Roswell Site in Chaves County, New Mexico, and the Barnwell Site in Barnwell County, South Carolina. EnergySolutions prepared Detailed Siting Reports (DSRs) that describe the overall character of each site and its local environment in sufficient detail to understand how it could be affected by the proposed GNEP facilities. A comprehensive review of the potentially affected environment showed that there were no foreseeable environmental impacts or regulatory prohibitions that would prevent each of the sites from serving as an effective host for GNEP. Each site was found to be of sufficient size to locate either or both of the planned GNEP Demonstration Facilities and to have sufficient room to provide suitably sized feed buffer and interim waste product storage capability. All three sites had water rights and access to a reliable source of water to support site operations. In each case, there is strong local and state interest in and support for siting the proposed GNEP facilities. (authors)« less

Collaborative efforts to improve system response to families who are experiencing child maltreatment and domestic violence.

PubMed

Banks, Duren; Dutch, Nicole; Wang, Kathleen

2008-07-01

The Greenbook demonstration initiative provided federal funding and other support to six communities to establish collaborations to plan and implement policy and practice changes in systems that serve families who are experiencing domestic violence and child maltreatment or child exposure to domestic violence. The demonstration sites established and organized collaborative groups in accordance with the Greenbook foundational principles and recommendations, including representation from multiple levels within the primary partner systems and other organizations, as well as the community. The sites struggled with how to engage consumers of the primary systems, however, and devoted a great deal of time to understanding and addressing organizational differences among the partners. Other salient collaborative influences included leadership, resources, trust, and commitment. The stakeholders noted that the collaborative relationships required a great deal of work but were ultimately one of the main successes of the initiative.

Wind Resource Assessment Report: Mille Lacs Indian Reservation, Minnesota

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

Jimenez, Antonio C.; Robichaud, Robi

The U.S. Environmental Protection Agency (EPA) launched the RE-Powering America's Land initiative to encourage development of renewable energy on potentially contaminated land and mine sites. EPA collaborated with the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) and the Mille Lacs Band of Chippewa Indians to evaluate the wind resource and examine the feasibility of a wind project at a contaminated site located on the Mille Lacs Indian Reservation in Minnesota. The wind monitoring effort involved the installation of a 60-m met tower and the collection of 18 months of wind data at multiple heights above the ground.more » This report focuses on the wind resource assessment, the estimated energy production of wind turbines, and an assessment of the economic feasibility of a potential wind project sited this site.« less

Origin recognition is the predominant role for DnaA-ATP in initiation of chromosome replication.

PubMed

Grimwade, Julia E; Rozgaja, Tania A; Gupta, Rajat; Dyson, Kyle; Rao, Prassanna; Leonard, Alan C

2018-05-25

In all cells, initiation of chromosome replication depends on the activity of AAA+ initiator proteins that form complexes with replication origin DNA. In bacteria, the conserved, adenosine triphosphate (ATP)-regulated initiator protein, DnaA, forms a complex with the origin, oriC, that mediates DNA strand separation and recruitment of replication machinery. Complex assembly and origin activation requires DnaA-ATP, which differs from DnaA-ADP in its ability to cooperatively bind specific low affinity sites and also to oligomerize into helical filaments. The degree to which each of these activities contributes to the DnaA-ATP requirement for initiation is not known. In this study, we compared the DnaA-ATP dependence of initiation from wild-type Escherichia coli oriC and a synthetic origin (oriCallADP), whose multiple low affinity DnaA sites bind DnaA-ATP and DnaA-ADP similarly. OriCallADP was fully occupied and unwound by DnaA-ADP in vitro, and, in vivo, oriCallADP suppressed lethality of DnaA mutants defective in ATP binding and ATP-specific oligomerization. However, loss of preferential DnaA-ATP binding caused over-initiation and increased sensitivity to replicative stress. The findings indicate both DnaA-ATP and DnaA-ADP can perform most of the mechanical functions needed for origin activation, and suggest that a key reason for ATP-regulation of DnaA is to control replication initiation frequency.

A new MCM modification cycle regulates DNA replication initiation

PubMed Central

Wei, Lei; Zhao, Xiaolan

2016-01-01

The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1 and activated in S phase to initiate replication. During this transition, the only known chemical change on MCM is the gain of multi-site phosphorylation that promotes cofactor recruitment. As replication initiation is intimately linked to multiple biological cues, additional changes on MCM can provide further regulatory points. Here, we describe a yeast MCM sumoylation cycle that negatively regulates replication. MCM subunits undergo sumoylation upon loading at origins in G1 prior to MCM phosphorylation. MCM sumoylation levels then decline as MCM phosphorylation levels rise, suggesting an inhibitory role in replication. Indeed, increasing MCM sumoylation impairs replication initiation through promoting the recruitment of a phosphatase that reduces MCM phosphorylation and activation. MCM sumoylation thus counterbalances kinase-based regulation to ensure accurate control of replication initiation. PMID:26854664

Integrating fine-scale soil data into species distribution models: preparing Soil Survey Geographic (SSURGO) data from multiple counties

Treesearch

Matthew P. Peters; Louis R. Iverson; Anantha M. Prasad; Steve N. Matthews

2013-01-01

Fine-scale soil (SSURGO) data were processed at the county level for 37 states within the eastern United States, initially for use as predictor variables in a species distribution model called DISTRIB II. Values from county polygon files converted into a continuous 30-m raster grid were aggregated to 4-km cells and integrated with other environmental and site condition...

Severe Unresponsive Hypoglycemia Associated with Neuroendocrine Tumor of Unknown Primary Site - 18 Years after Rectal Cancer Surgery. Case Report.

PubMed

Rusu, Octavia Cristina; Costea, Radu Virgil; Popa, Cristian Constantin; Iliesiu, Andreea; Dumitru, Adrian; Becheanu, Gabriel; Neagu, Stefan Ilie

2015-09-01

Neuroendocrine tumors are derived from cells that have the unique ability to synthesize, store and secrete a variety of metabolically active substances, peptides and amines, characteristic of the tissue of origin, which can cause distinct clinical syndromes. We present the case of a 58-year-old patient diagnosed and surgically treated in January 1996 for stage III inferior rectal cancer, who was readmitted after 18 years presenting persistent diarrheic syndrome and asthenia. Investigations performed (abdominal CT) showed multiple liver metastases, initially suspected as being related to the rectal cancer. Biopsy of liver metastases and pathological and immunohistochemical analysis demonstrated the neuroendocrine origin (moderately differentiated neuroendocrine tumor). Seven months after the identification of liver metastases and after initiation of oncological therapy with Interferon and Somatostatin, the patient presented severe hypoglycemia (serum glucose 13-70 mg/dl) proved to be due to insulin-like factors (serum insulin level 64.9 ìU/ml) secreted by metastases. Due to the aggressive evolution of neuroendocrine tumor, with multiple episodes of severe hypoglycemia, resistant to treatment, the patient died approximately one month after the occurrence of hypoglycemic episodes. Despite comprehensive tests (abdominal CT scan, colonoscopy, bone scintigraphy and PET/CT), the primary site of the neuroendocrine tumors remained unknown.

Multiple limbal haemangiosarcomas in a border collie dog: management by lamellar keratectomy/sclerectomy and strontium-90 beta plesiotherapy.

PubMed

Donaldson, D; Sansom, J; Murphy, S; Scase, T

2006-09-01

An eight-year-old, neutered, male border collie dog was presented with a six-week history of left ocular discomfort and a raised, red mass at the lateral limbus. The right eye had been enucleated approximately 12 months previously following suspected trauma when the eye had become red and painful. The mass was excised using superficial keratectomy/sclerectomy and the surgery site was treated with strontium-90 beta radiation. Histopathological findings were consistent with a diagnosis of haemangiosarcoma. Immunohistochemical staining showed uniform expression of CD31 in neoplastic cells, confirming their endothelial origin. Two further treatments with strontium-90 beta radiation were applied to the surgical site at weekly intervals. Twenty-six weeks after surgery, a second, raised, red limbal mass became apparent at the medial limbus of the left eye. Surgical excision and adjuvant strontium-90 beta plesiotherapy were performed as described for the initial tumour. Routine histopathological analysis confirmed haemangiosarcoma at this site. Eighty-six weeks following the initial presentation, no recurrence of ocular haemangiosarcoma was evident.

Characterization of Transcription from TATA-Less Promoters: Identification of a New Core Promoter Element XCPE2 and Analysis of Factor Requirements

PubMed Central

Anish, Ramakrishnan; Hossain, Mohammad B.; Jacobson, Raymond H.; Takada, Shinako

2009-01-01

Background More than 80% of mammalian protein-coding genes are driven by TATA-less promoters which often show multiple transcriptional start sites (TSSs). However, little is known about the core promoter DNA sequences or mechanisms of transcriptional initiation for this class of promoters. Methodology/Principal Findings Here we identify a new core promoter element XCPE2 (X core promoter element 2) (consensus sequence: A/C/G-C-C/T-C-G/A-T-T-G/A-C-C/A+1-C/T) that can direct specific transcription from the second TSS of hepatitis B virus X gene mRNA. XCPE2 sequences can also be found in human promoter regions and typically appear to drive one of the start sites within multiple TSS-containing TATA-less promoters. To gain insight into mechanisms of transcriptional initiation from this class of promoters, we examined requirements of several general transcription factors by in vitro transcription experiments using immunodepleted nuclear extracts and purified factors. Our results show that XCPE2-driven transcription uses at least TFIIB, either TFIID or free TBP, RNA polymerase II (RNA pol II) and the MED26-containing mediator complex but not Gcn5. Therefore, XCPE2-driven transcription can be carried out by a mechanism which differs from previously described TAF-dependent mechanisms for initiator (Inr)- or downstream promoter element (DPE)-containing promoters, the TBP- and SAGA (Spt-Ada-Gcn5-acetyltransferase)-dependent mechanism for yeast TATA-containing promoters, or the TFTC (TBP-free-TAF-containing complex)-dependent mechanism for certain Inr-containing TATA-less promoters. EMSA assays using XCPE2 promoter and purified factors further suggest that XCPE2 promoter recognition requires a set of factors different from those for TATA box, Inr, or DPE promoter recognition. Conclusions/Significance We identified a new core promoter element XCPE2 that are found in multiple TSS-containing TATA-less promoters. Mechanisms of promoter recognition and transcriptional initiation for XCPE2-driven promoters appear different from previously shown mechanisms for classical promoters that show single “focused” TSSs. Our studies provide insight into novel mechanisms of RNA Pol II transcription from multiple TSS-containing TATA-less promoters. PMID:19337366

Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site.

PubMed

Fuchs, Gabriele; Petrov, Alexey N; Marceau, Caleb D; Popov, Lauren M; Chen, Jin; O'Leary, Seán E; Wang, Richard; Carette, Jan E; Sarnow, Peter; Puglisi, Joseph D

2015-01-13

Translation initiation can occur by multiple pathways. To delineate these pathways by single-molecule methods, fluorescently labeled ribosomal subunits are required. Here, we labeled human 40S ribosomal subunits with a fluorescent SNAP-tag at ribosomal protein eS25 (RPS25). The resulting ribosomal subunits could be specifically labeled in living cells and in vitro. Using single-molecule Förster resonance energy transfer (FRET) between RPS25 and domain II of the hepatitis C virus (HCV) internal ribosome entry site (IRES), we measured the rates of 40S subunit arrival to the HCV IRES. Our data support a single-step model of HCV IRES recruitment to 40S subunits, irreversible on the initiation time scale. We furthermore demonstrated that after binding, the 40S:HCV IRES complex is conformationally dynamic, undergoing slow large-scale rearrangements. Addition of translation extracts suppresses these fluctuations, funneling the complex into a single conformation on the 80S assembly pathway. These findings show that 40S:HCV IRES complex formation is accompanied by dynamic conformational rearrangements that may be modulated by initiation factors.

MDC-Analyzer: a novel degenerate primer design tool for the construction of intelligent mutagenesis libraries with contiguous sites.

PubMed

Tang, Lixia; Wang, Xiong; Ru, Beibei; Sun, Hengfei; Huang, Jian; Gao, Hui

2014-06-01

Recent computational and bioinformatics advances have enabled the efficient creation of novel biocatalysts by reducing amino acid variability at hot spot regions. To further expand the utility of this strategy, we present here a tool called Multi-site Degenerate Codon Analyzer (MDC-Analyzer) for the automated design of intelligent mutagenesis libraries that can completely cover user-defined randomized sequences, especially when multiple contiguous and/or adjacent sites are targeted. By initially defining an objective function, the possible optimal degenerate PCR primer profiles could be automatically explored using the heuristic approach of Greedy Best-First-Search. Compared to the previously developed DC-Analyzer, MDC-Analyzer allows for the existence of a small amount of undesired sequences as a tradeoff between the number of degenerate primers and the encoded library size while still providing all the benefits of DC-Analyzer with the ability to randomize multiple contiguous sites. MDC-Analyzer was validated using a series of randomly generated mutation schemes and experimental case studies on the evolution of halohydrin dehalogenase, which proved that the MDC methodology is more efficient than other methods and is particularly well-suited to exploring the sequence space of proteins using data-driven protein engineering strategies.

Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression

NASA Astrophysics Data System (ADS)

Lengyel, Iván M.; Morelli, Luis G.

2017-04-01

Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products. By tuning the threshold for repression, we show that multiple binding sites can also suppress fluctuations. Our results highlight possible roles for the presence of multiple binding sites of negative autoregulators.

Fatigue analysis of multiple site damage at a row of holes in a wide panel

NASA Technical Reports Server (NTRS)

Buhler, Kimberley; Grandt, Alten F., Jr.; Moukawsher, E. J.

1994-01-01

This paper is concerned with predicting the fatigue life of unstiffened panels which contain multiple site damage (MSD). The initial damage consists of through-the-thickness cracks emanating from a row of holes in the center of a finite width panel. A fracture mechanics analysis has been developed to predict the growth, interaction, and coalescence of the various cracks which propagate in the panel. A strain-life analysis incorporating Neuber's rule for notches, and Miner's rule for cumulative damage, is also employed to predict crack initiation for holes without initial cracking. This analysis is compared with the results of a series of fatigue tests on 2024-T3 aluminum panels, and is shown to do an excellent job of predicting the influence of MSD on the fatigue life of nine inch wide specimens. Having established confidence in the ability to analyze the influence of MSD on fatigue life, a parametric study is conducted to examine the influence of various MSD scenarios in an unstiffened panel. The numerical study considered 135 cases in all, with the parametric variables being the applied cyclic stress level, the lead crack geometry, and the number and location of MSD cracks. The numerical analysis provides details for the manner in which lead cracks and MSD cracks grow and coalesce leading to final failure. The results indicate that MSD located adjacent to lead cracks is the most damaging configuration, while for cases without lead cracks, MSD clusters which are not separated by uncracked holes are most damaging.

Observations of the Ion Signatures of Double Merging and the Formation of Newly Closed Field Lines

NASA Technical Reports Server (NTRS)

Chandler, Michael O.; Avanov, Levon A.; Craven, Paul D.

2007-01-01

Observations from the Polar spacecraft, taken during a period of northward interplanetary magnetic field (IMF) show magnetosheath ions within the magnetosphere with velocity distributions resulting from multiple merging sites along the same field line. The observations from the TIDE instrument show two separate ion energy-time dispersions that are attributed to two widely separated (-20Re) merging sites. Estimates of the initial merging times show that they occurred nearly simultaneously (within 5 minutes.) Along with these populations, cold, ionospheric ions were observed counterstreaming along the field lines. The presence of such ions is evidence that these field lines are connected to the ionosphere on both ends. These results are consistent with the hypothesis that double merging can produce closed field lines populated by solar wind plasma. While the merging sites cannot be unambiguously located, the observations and analyses favor one site poleward of the northern cusp and a second site at low latitudes.

Extensive variation, but not local adaptation in an Australian alpine daisy.

PubMed

Hirst, Megan J; Sexton, Jason P; Hoffmann, Ary A

2016-08-01

Alpine plants often occupy diverse habitats within a similar elevation range, but most research on local adaptation in these plants has focused on elevation gradients. In testing for habitat-related local adaptation, local effects on seed quality and initial plant growth should be considered in designs that encompass multiple populations and habitats. We tested for local adaptation across alpine habitats in a morphologically variable daisy species, Brachyscome decipiens, in the Bogong High Plains in Victoria, Australia. We collected seed from different habitats, controlled for maternal effects through initial seed size estimates, and characterized seedling survival and growth in a field transplant experiment. We found little evidence for local adaptation for survival or plant size, based on three adaptation measures: Home versus Away, Local versus Foreign, and Sympatric versus Allopatric (SA). The SA measure controlled for planting site and population (site-of-origin) effects. There were significant differences due to site-of-origin and planting site effects. An important confounding factor was the size of plants directly after transplantation of seedlings, which had a large impact on subsequent seedling survival and growth. Initial differences in plant width and height influenced subsequent survival across the growing season but in opposing directions: wide plants had higher survival, but tall plants had lower survival. In an additional controlled garden experiment at Cranbourne Royal Botanic Gardens, site-of-origin effects detected in the field experiments disappeared under more benign homogeneous conditions. Although B. decipiens from different source areas varied significantly when grown across a range of alpine habitats, these differences did not translate into a local or habitat-related fitness advantage. This lack of local advantage may signal weak past selection, and/or weak adaptive transgeneration (plasticity) effects.

Multiple-methods investigation of recharge at a humid-region fractured rock site, Pennsylvania, USA

USGS Publications Warehouse

Heppner, C.S.; Nimmo, J.R.; Folmar, G.J.; Gburek, W.J.; Risser, D.W.

2007-01-01

Lysimeter-percolate and well-hydrograph analyses were combined to evaluate recharge for the Masser Recharge Site (central Pennsylvania, USA). In humid regions, aquifer recharge through an unconfined low-porosity fractured-rock aquifer can cause large magnitude water-table fluctuations over short time scales. The unsaturated hydraulic characteristics of the subsurface porous media control the magnitude and timing of these fluctuations. Data from multiple sets of lysimeters at the site show a highly seasonal pattern of percolate and exhibit variability due to both installation factors and hydraulic property heterogeneity. Individual event analysis of well hydrograph data reveals the primary influences on water-table response, namely rainfall depth, rainfall intensity, and initial water-table depth. Spatial and seasonal variability in well response is also evident. A new approach for calculating recharge from continuous water-table elevation records using a master recession curve (MRC) is demonstrated. The recharge estimated by the MRC approach when assuming a constant specific yield is seasonal to a lesser degree than the recharge estimate resulting from the lysimeter analysis. Partial reconciliation of the two recharge estimates is achieved by considering a conceptual model of flow processes in the highly-heterogeneous underlying fractured porous medium. ?? Springer-Verlag 2007.

40 CFR 62.14356 - Compliance schedules and increments of progress.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to...) to initiate on-site construction or initiate on-site installation of emission collection and/or control equipment. (3) Initiate on-site construction: Initiate on-site construction or initiate on-site...

40 CFR 62.14356 - Compliance schedules and increments of progress.

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTANTS Federal Plan Requirements for Municipal Solid Waste Landfills That Commenced Construction Prior to...) to initiate on-site construction or initiate on-site installation of emission collection and/or control equipment. (3) Initiate on-site construction: Initiate on-site construction or initiate on-site...

Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment?

PubMed

Sayed, Blayne A; Christy, Alison L; Walker, Margaret E; Brown, Melissa A

2010-06-15

Mast cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis, a rodent model of the human demyelinating disease multiple sclerosis. Yet their site and mode of action is unknown. In both diseases, myelin-specific T cells are initially activated in peripheral lymphoid organs. However, for disease to occur, these cells must enter the immunologically privileged CNS through a breach in the relatively impermeable blood-brain barrier. In this study, we demonstrate that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry. Through the expression of TNF, mast cells recruit an early wave of neutrophils to the CNS. We propose that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell influx and myelin damage. These findings provide specific targets for intervention in multiple sclerosis as well as other immune-mediated CNS diseases.

Lymphocutaneous sporotrichosis in an adolescent girl presenting as mycetoma.

PubMed

Tilak, Ragini; Kumari, Varsha; Bansal, Manish; Sharma, Taniya; Pandey, Shyam Sunder

2012-09-01

A 13-year-old girl presented with multiple painless purulent ulcers with raised borders on the medial aspect of the sole of her right foot associated with inguinal lymphadenopathy for the past 4 years. There was history of local trauma at the site prior to the formation of ulcers. There were no other significant associated signs or symptoms. The patient was initially treated with multiple antibiotics with minimal improvement. Fungal cultures of biopsy specimens demonstrated the presence of colonies of Sporothrix schenckii thus confirming the diagnosis of sporotrichosis. Oral itraconazole at the dose of 100 mg twice daily was initiated with marked response at 4 weeks. This case demonstrated a rare morphological presentation of the lymphocutaneous sporotrichosis as mycetoma. The possible diagnosis of sporotrichosis should be kept in mind in such a clinical presentation not responding to antibiotics. Cutaneous sporotrichosis should be diagnosed and treated as early as possible because untreated cases may disseminate to cause visceral involvement with fatal outcome in immunocompromised patients.

Flight initiation and maintenance deficits in flies with genetically altered biogenic amine levels.

PubMed

Brembs, Björn; Christiansen, Frauke; Pflüger, Hans Joachim; Duch, Carsten

2007-10-10

Insect flight is one of the fastest, most intense and most energy-demanding motor behaviors. It is modulated on multiple levels by the biogenic amine octopamine. Within the CNS, octopamine acts directly on the flight central pattern generator, and it affects motivational states. In the periphery, octopamine sensitizes sensory receptors, alters muscle contraction kinetics, and enhances flight muscle glycolysis. This study addresses the roles for octopamine and its precursor tyramine in flight behavior by genetic and pharmacological manipulation in Drosophila. Octopamine is not the natural signal for flight initiation because flies lacking octopamine [tyramine-beta-hydroxylase (TbetaH) null mutants] can fly. However, they show profound differences with respect to flight initiation and flight maintenance compared with wild-type controls. The morphology, kinematics, and development of the flight machinery are not impaired in TbetaH mutants because wing-beat frequencies and amplitudes, flight muscle structure, and overall dendritic structure of flight motoneurons are unaffected in TbetaH mutants. Accordingly, the flight behavior phenotypes can be rescued acutely in adult flies. Flight deficits are rescued by substituting octopamine but also by blocking the receptors for tyramine, which is enriched in TbetaH mutants. Conversely, ablating all neurons containing octopamine or tyramine phenocopies TbetaH mutants. Therefore, both octopamine and tyramine systems are simultaneously involved in regulating flight initiation and maintenance. Different sets of rescue experiments indicate different sites of action for both amines. These findings are consistent with a complex system of multiple amines orchestrating the control of motor behaviors on multiple levels rather than single amines eliciting single behaviors.

A Hierarchical Analysis of Tree Growth and Environmental Drivers Across Eastern US Temperate Forests

NASA Astrophysics Data System (ADS)

Mantooth, J.; Dietze, M.

2014-12-01

Improving predictions of how forests in the eastern United States will respond to future global change requires a better understanding of the drivers of variability in tree growth rates. Current inventory data lack the temporal resolution to characterize interannual variability, while existing growth records lack the extent required to assess spatial scales of variability. Therefore, we established a network of forest inventory plots across ten sites across the eastern US, and measured growth in adult trees using increment cores. Sites were chosen to maximize climate space explored, while within sites, plots were spread across primary environmental gradients to explore landscape-level variability in growth. Using the annual growth record available from tree cores, we explored the responses of trees to multiple environmental covariates over multiple spatial and temporal scales. We hypothesized that within and across sites growth rates vary among species, and that intraspecific growth rates increase with temperature along a species' range. We also hypothesized that trees show synchrony in growth responses to landscape-scale climatic changes. Initial analyses of growth increments indicate that across sites, trees with intermediate shade tolerance, e.g. Red Oak (Quercus rubra), tend to have the highest growth rates. At the site level, there is evidence for synchrony in response to large-scale climatic events (e.g. prolonged drought and above average temperatures). However, growth responses to climate at the landscape scale have yet to be detected. Our current analysis utilizes hierarchical Bayesian state-space modeling to focus on growth responses of adult trees to environmental covariates at multiple spatial and temporal scales. This predictive model of tree growth currently incorporates observed effects at the individual, plot, site, and landscape scale. Current analysis using this model shows a potential slowing of growth in the past decade for two sites in the northeastern US (Harvard Forest and Bartlett Experimental Forest), however more work is required to determine the robustness of this trend. Finally, these observations are being incorporated into ecosystem models using the Brown Dog informatics tools and the Predictive Ecosystem Analyzer (PEcAn) data assimilation workflow.

Endocarditis and Stroke

PubMed Central

GRECU, Nicolae; TIU, Cristina; TERECOASA, Elena; BAJENARU, Ovidiu

2014-01-01

Endocarditis is an important, although less common, cause of cerebral embolism. All forms of endocarditis share an initial common pathophysiologic pathway, best illustrated by the non-bacterial thrombotic form, but also a final potential for embolization. Stroke associated with endocarditis has signifficant mortality and morbidity rates, especially due to the frequent concomitant multiple sites of brain embolization. In this article we aim to briefly review endocarditis with a focus on stroke as a complication, while also presenting case correlates from our department. PMID:25705308

Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

PubMed Central

Hutchinson, John N.; Raj, Towfique; Fagerness, Jes; Stahl, Eli; Viloria, Fernando T.; Gimelbrant, Alexander; Seddon, Johanna; Daly, Mark; Chess, Andrew; Plenge, Robert

2014-01-01

We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results. PMID:24911414

Uterine cervical cancer with brain metastasis as the initial site of presentation.

PubMed

Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

2015-07-01

Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

Ribosome profiling: a Hi-Def monitor for protein synthesis at the genome-wide scale

PubMed Central

Michel, Audrey M; Baranov, Pavel V

2013-01-01

Ribosome profiling or ribo-seq is a new technique that provides genome-wide information on protein synthesis (GWIPS) in vivo. It is based on the deep sequencing of ribosome protected mRNA fragments allowing the measurement of ribosome density along all RNA molecules present in the cell. At the same time, the high resolution of this technique allows detailed analysis of ribosome density on individual RNAs. Since its invention, the ribosome profiling technique has been utilized in a range of studies in both prokaryotic and eukaryotic organisms. Several studies have adapted and refined the original ribosome profiling protocol for studying specific aspects of translation. Ribosome profiling of initiating ribosomes has been used to map sites of translation initiation. These studies revealed the surprisingly complex organization of translation initiation sites in eukaryotes. Multiple initiation sites are responsible for the generation of N-terminally extended and truncated isoforms of known proteins as well as for the translation of numerous open reading frames (ORFs), upstream of protein coding ORFs. Ribosome profiling of elongating ribosomes has been used for measuring differential gene expression at the level of translation, the identification of novel protein coding genes and ribosome pausing. It has also provided data for developing quantitative models of translation. Although only a dozen or so ribosome profiling datasets have been published so far, they have already dramatically changed our understanding of translational control and have led to new hypotheses regarding the origin of protein coding genes. © 2013 John Wiley & Sons, Ltd. PMID:23696005

Structure of the human gene encoding the protein repair L-isoaspartyl (D-aspartyl) O-methyltransferase.

PubMed

DeVry, C G; Tsai, W; Clarke, S

1996-11-15

The protein L-isoaspartyl/D-aspartyl O-methyltransferase (EC 2.1.1.77) catalyzes the first step in the repair of proteins damaged in the aging process by isomerization or racemization reactions at aspartyl and asparaginyl residues. A single gene has been localized to human chromosome 6 and multiple transcripts arising through alternative splicing have been identified. Restriction enzyme mapping, subcloning, and DNA sequence analysis of three overlapping clones from a human genomic library in bacteriophage P1 indicate that the gene spans approximately 60 kb and is composed of 8 exons interrupted by 7 introns. Analysis of intron/exon splice junctions reveals that all of the donor and acceptor splice sites are in agreement with the mammalian consensus splicing sequence. Determination of transcription initiation sites by primer extension analysis of poly(A)+ mRNA from human brain identifies multiple start sites, with a major site 159 nucleotides upstream from the ATG start codon. Sequence analysis of the 5'-untranslated region demonstrates several potential cis-acting DNA elements including SP1, ETF, AP1, AP2, ARE, XRE, CREB, MED-1, and half-palindromic ERE motifs. The promoter of this methyltransferase gene lacks an identifiable TATA box but is characterized by a CpG island which begins approximately 723 nucleotides upstream of the major transcriptional start site and extends through exon 1 and into the first intron. These features are characteristic of housekeeping genes and are consistent with the wide tissue distribution observed for this methyltransferase activity.

Modeling Land Application of Food-Processing Wastewater in the Central Valley, California

NASA Astrophysics Data System (ADS)

Rubin, Y.; Benito, P.; Miller, G.; McLaughlin, J.; Hou, Z.; Hermanowicz, S.; Mayer, U.

2007-12-01

California's Central Valley contains over 640 food-processing plants, serving a multi-billion dollar agricultural industry. These processors consume approximately 7.9 x 107 m3 of water per year. Approximately 80% of these processors discharge the resulting wastewater, which is typically high in organic matter, nitrogen, and salts, to land, and many of these use land application as a treatment method. Initial investigations revealed elevated salinity levels to be the most common form of groundwater degradation near land application sites, followed by concentrations of nitrogen compounds, namely ammonia and nitrate. Enforcement actions have been taken against multiple food processors, and the regulatory boards have begun to re-examine the land disposal permitting process. This paper summarizes a study that was commissioned in support of these actions. The study has multiple components which will be reviewed briefly, including: (1) characterization of the food-processing related waste stream; (2) fate and transport of the effluent waste stream in the unsaturated zone at the land application sites; (3) fate and transport of the effluent waste stream at the regional scale; (4) predictive uncertainty due to spatial variability and data scarcity at the land application sites and at the regional scale; (5) problem mitigation through off-site and in-situ actions; (6) long-term solutions. The emphasis of the talk will be placed on presenting and demonstrating a stochastic framework for modeling the transport and attenuation of these wastes in the vadose zone and in the saturated zone, and the related site characterization needs, as affected by site conditions, water table depth, waste water application rate, and waste constituent concentrations.

Regulatory impediments jeopardizing the conduct of clinical trials in Europe funded by the National Institutes of Health

PubMed Central

Neaton, James D; Babiker, Abdel; Bohnhorst, Mark; Darbyshire, Janet; Denning, Eileen; Frishman, Arnie; Grarup, Jesper; Larson, Gregg; Lundgren, Jens

2011-01-01

Background A number of reports have highlighted problems of conducting publicly funded trials in Europe as a consequence of the European Union (EU) Clinical Trials Directive. The impact of the EU Directive on multi-national trials, which include sites in Europe that are funded by the US National Institutes of Health (NIH) have not been described. Methods Four problems in the conduct of two international HIV treatment trials funded by NIH in the EU are described: (1) conflicting regulations on the continuing review of protocols by Institutional Review Boards/Research Ethics Committees; (2) US regulations requiring Federalwide Assurances for sites which are only partially funded by NIH; (3) EU guidance on the designation of studies as a trial of an investigational medicinal product; and (4) EU guidance on trial sponsorship and the requirements for insurance and indemnification. Following the description of the problems, recommendations for improving global collaborations are made to the US Office of Human Research Protections, to NIH, and to the EU and its Member States. Results A lack of harmonization of regulations at multiple levels caused enrollment in one study to be interrupted for several months and delayed for one year the initiation of another study aimed at obtaining definitive evidence to guide the timing of the initiation of antiretroviral therapy for individuals infected with HIV. The delays and the purchase of insurance resulted in substantial increases in trial costs and caused substantial disruption at clinical sites among staff and study participants. Limitations The problems cited and recommendations made pertain to trials funded by NIH and conducted by sites in the EU. There are many other challenges in the conduct of international research, public and private, that global harmonization would alleviate. Conclusions Disharmony, at multiple levels, in international regulations and guidelines is stifling publicly funded global research. International scientific organizations and government groups should make the documentation and solution of these problems a priority. PMID:20729252

SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle

PubMed Central

Figueroa-Romero, Claudia; Iñiguez-Lluhí, Jorge A.; Stadler, Julia; Chang, Chuang-Rung; Arnoult, Damien; Keller, Peter J.; Hong, Yu; Blackstone, Craig; Feldman, Eva L.

2009-01-01

Dynamin-related protein (Drp) 1 is a key regulator of mitochondrial fission and is composed of GTP-binding, Middle, insert B, and C-terminal GTPase effector (GED) domains. Drp1 associates with mitochondrial fission sites and promotes membrane constriction through its intrinsic GTPase activity. The mechanisms that regulate Drp1 activity remain poorly understood but are likely to involve reversible post-translational modifications, such as conjugation of small ubiquitin-like modifier (SUMO) proteins. Through a detailed analysis, we find that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions and demonstrate that Drp1 is a direct target of SUMO modification by all three SUMO isoforms. While Drp1 does not harbor consensus SUMOylation sequences, our analysis identified2 clusters of lysine residues within the B domain that serve as noncanonical conjugation sites. Although initial analysis indicates that mitochondrial recruitment of ectopically expressed Drp1 in response to staurosporine is unaffected by loss of SUMOylation, we find that Drp1 SUMOylation is enhanced in the context of the K38A mutation. This dominant-negative mutant, which is deficient in GTP binding and hydrolysis, does not associate with mitochondria and prevents normal mitochondrial fission. This finding suggests that SUMOylation of Drp1 is linked to its activity cycle and is influenced by Drp1 localization.—Figueroa-Romero, C., Iñiguez-Lluhí, J. A., Stadler, J., Chang, C.-R., Arnoult, D., Keller, P. J., Hong, Y., Blackstone, C., Feldman, E. L. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. PMID:19638400

Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases.

PubMed

Al-Hallaq, Hania A; Chmura, Steven; Salama, Joseph K; Winter, Kathryn A; Robinson, Clifford G; Pisansky, Thomas M; Borges, Virginia; Lowenstein, Jessica R; McNulty, Susan; Galvin, James M; Followill, David S; Timmerman, Robert D; White, Julia R; Xiao, Ying; Matuszak, Martha M

In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection. Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed. Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity. NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Influence of Translation Initiation on Organellar Protein Targeting in Arabidopsis

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

Sally A. Mackenzie

2011-04-18

A primary focus of the Mackenzie laboratory is the elucidation of processes and machinery for mitochondrial genome maintenance and transmission in higher plants. We have found that numerous organellar DNA maintenance components in plants appear to be dual targeted to mitochondria and plastids. Of particular interest was the observation that some twin (tandemly arrayed) dual targeting presequences appeared to utilize non-AUG alternative translation initiation, allowing for multiple translation starts at a single gene. Two aspects of this phenomenon were of particular interest: (1) Alternative translation initiation might provide a mechanism to regulate protein targeting temporally and spatially, a possibility thatmore » had not been demonstrated previously, and (2) alternative translation initiation might occur in genes involved in nuclear-controlled mitochondrial genome recombination, thought to be exclusively mitochondrial in their function. During the course of this research, we pursued three aims, with an emphasis on two specific genes of interest: POLgamma2, an organellar DNA polymerase, and MSH1, a MutS homolog thought to participate in mitochondrial, but not plastid, genome recombination surveillance. Our aims were to (1) Identify additional genes within Arabidopsis and other genomes that employ non-AUG alternative translation initiation, (2) Locate sequences upstream to the annotated AUG that confer alternative non-AUG translation initiation activity, and (3) Identify cis and trans factors that influence start site selection in genes with non-AUG starts. Toward these ends, we have shown that non-AUG initiation occurs in a number of genes, likely influencing targeting behavior of the protein. We have also shown that start site selection is strongly influenced by Kozak consensus sequence environment, indicating that alternative translation initiation in plants occurs by relaxation of ribosome scanning.« less

An evolutionary communications scenario for Mars exploration

NASA Technical Reports Server (NTRS)

Stevenson, Steven M.

1987-01-01

As Mars exploration grows in complexity with time, the corresponding communication needs will grow in variety and complexity also. From initial Earth/Mars links, further needs will arise for complete surface connectivity for the provision of navigation, position location, and voice, data, and video communications services among multiple Mars bases and remote exploration sites. This paper addresses the likely required communication functions over the first few decades of Martian exploration and postulates systems for providing these services. Required technologies are identified and development requirements indicated.

A risk assessment method for multi-site damage

NASA Astrophysics Data System (ADS)

Millwater, Harry Russell, Jr.

This research focused on developing probabilistic methods suitable for computing small probabilities of failure, e.g., 10sp{-6}, of structures subject to multi-site damage (MSD). MSD is defined as the simultaneous development of fatigue cracks at multiple sites in the same structural element such that the fatigue cracks may coalesce to form one large crack. MSD is modeled as an array of collinear cracks with random initial crack lengths with the centers of the initial cracks spaced uniformly apart. The data used was chosen to be representative of aluminum structures. The structure is considered failed whenever any two adjacent cracks link up. A fatigue computer model is developed that can accurately and efficiently grow a collinear array of arbitrary length cracks from initial size until failure. An algorithm is developed to compute the stress intensity factors of all cracks considering all interaction effects. The probability of failure of two to 100 cracks is studied. Lower bounds on the probability of failure are developed based upon the probability of the largest crack exceeding a critical crack size. The critical crack size is based on the initial crack size that will grow across the ligament when the neighboring crack has zero length. The probability is evaluated using extreme value theory. An upper bound is based on the probability of the maximum sum of initial cracks being greater than a critical crack size. A weakest link sampling approach is developed that can accurately and efficiently compute small probabilities of failure. This methodology is based on predicting the weakest link, i.e., the two cracks to link up first, for a realization of initial crack sizes, and computing the cycles-to-failure using these two cracks. Criteria to determine the weakest link are discussed. Probability results using the weakest link sampling method are compared to Monte Carlo-based benchmark results. The results indicate that very small probabilities can be computed accurately in a few minutes using a Hewlett-Packard workstation.

Antagonistic interactions of an arsenic-containing mixture in a multiple organ carcinogenicity bioassay.

PubMed

Pott, W A; Benjamin, S A; Yang, R S

1998-11-27

Inorganic arsenic (As), 1,2-dichloroethane (DCE), vinyl chloride (VC) and trichloroethylene (TCE) are frequently identified as groundwater contaminants near hazardous waste disposal sites. While the carcinogenicity of each of these chemicals has been extensively studied individually, little information exists regarding their carcinogenic potential in combination. Therefore, we investigated the carcinogenic promoting potential of chemical mixtures containing arsenic, DCE, VC and TCE following multiple initiator administration in a multiple organ carcinogenicity bioassay (N. Ito, T. Shirai, S. Fukushima, Medium-term bioassay for carcinogens using multiorgan models, in: N. Ito, H. Sugano (Eds.), Modification of Tumor Development in Rodents, Prog. Exp. Tumor Res., 33, 41-57, Basel, Karger, 1991). Our results reveal a dose-responsive antagonistic effect of this four-chemical mixture on the development of preneoplastic hepatic lesions (altered hepatocellular foci and glutathione S-transferase pi positive foci) as well as bronchioalveolar hyperplasia and adenoma formation.

Ferrocenemonocarboxylic-HRP@Pt nanoparticles labeled RCA for multiple amplification of electro-immunosensing.

PubMed

Su, Huilan; Yuan, Ruo; Chai, Yaqin; Mao, Li; Zhuo, Ying

2011-07-15

A multiple amplification immunoassay was proposed to detect alpha-fetoprotein (AFP), which was based on ferrocenemonocarboxylic-HRP conjugated on Pt nanoparticles as labels for rolling circle amplification (RCA). Firstly, the capture antibody (anti-AFP) was immobilized on glass carbon electrode (GCE) deposited nano-sized gold particles. After a typical immuno-sandwich protocol, primary DNA was immobilized by labeling secondary antibody, which acted as a precursor to initiate RCA. The products of RCA provide large amount of sites to link detection DNAs, which were labeled by signal probes (ferrocenemonocarboxylic) and horseradish peroxidase (HRP). Moreover, the enzymatic amplification signals could be produced by the catalysis of HRP and Pt nanoparticles with the addition of H₂O₂. These lead to multiple amplification signals monitoring by electrochemical instrument and further resulted in high sensitivity of the immunoassay with the detection limit of 1.7 pg/mL. Copyright © 2011 Elsevier B.V. All rights reserved.

Hemoglobin Cleavage Site-Specificity of the Plasmodium falciparum Cysteine Proteases Falcipain-2 and Falcipain-3

PubMed Central

Subramanian, Shoba; Hardt, Markus; Choe, Youngchool; Niles, Richard K.; Johansen, Eric B.; Legac, Jennifer; Gut, Jiri; Kerr, Iain D.; Craik, Charles S.; Rosenthal, Philip J.

2009-01-01

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P1 – P4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P2 position. Second, with overlapping peptides spanning α and β globin and proteolysis-dependent 18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents. PMID:19357776

Reconstructing the Initial Human Occupation of the Northern Tibetan Plateau

NASA Astrophysics Data System (ADS)

Madsen, David; Brantingham, Jeffrey; Sun, Yongjuan; Rhode, David; Mingjie, Yi; Perreault, Charles

2017-04-01

We identified and dated 20 archaeological sites, many containing multiple occupations, above 3000 m on the northeastern margin of the Tibetan Plateau (TP) during a decade-long Sino-American Tibet Paleolithic Project. The ages of these sites are controlled by 68 AMS radiocarbon dates, as well as associated luminescence age estimates. Together these sites suggest the initial occupation of the high northern TP occurred in two phases: 1) an early phase dating to 16-8 ka, characterized by short-term hunting camps occupied by small groups of foragers likely originating from lower elevation, but relatively nearby, base camps; and 2) a later phase dating to 8-5 ka, characterized by longer-term residential camps likely occupied by larger family groups also originating from nearby lower elevations. Whether or not these later family groups were full-time foragers or were pastoralists linked to farming communities remains under investigation. This pattern closely matches genetically-based estimates of rapid population increases. Both phases appear related to major climatic episodes: a period of rapid post-glacial warming, spread of higher elevation alpine grassland/meadow environments, and enhanced populations of larger herbivores; and a period of mid-Holocene warming that allowed farming/pastoralism to develop at higher elevations. We identified no sites dating to the LGM or earlier and genetic separation of Tibetan populations likely occurred on the lower elevation plateau margins. By 5 ka essentially modern settlement/subsistence patterns were established.

Prdm9 controls activation of mammalian recombination hotspots.

PubMed

Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

2010-02-12

Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

Evolution of the Florida Launch Site Architecture: Embracing Multiple Customers, Enhancing Launch Opportunities

NASA Technical Reports Server (NTRS)

Colloredo, Scott; Gray, James A.

2011-01-01

The impending conclusion of the Space Shuttle Program and the Constellation Program cancellation unveiled in the FY2011 President's budget created a large void for human spaceflight capability and specifically launch activity from the Florida launch Site (FlS). This void created an opportunity to re-architect the launch site to be more accommodating to the future NASA heavy lift and commercial space industry. The goal is to evolve the heritage capabilities into a more affordable and flexible launch complex. This case study will discuss the FlS architecture evolution from the trade studies to select primary launch site locations for future customers, to improving infrastructure; promoting environmental remediation/compliance; improving offline processing, manufacturing, & recovery; developing range interface and control services with the US Air Force, and developing modernization efforts for the launch Pad, Vehicle Assembly Building, Mobile launcher, and supporting infrastructure. The architecture studies will steer how to best invest limited modernization funding from initiatives like the 21 st elSe and other potential funding.

Characterization of the human UDP-galactose:ceramide galactosyltransferase gene promoter.

PubMed

Tencomnao, T; Yu, R K; Kapitonov, D

2001-02-16

UDP-galactose:ceramide galactosyltransferase (CGT, EC 2.4.1.45) is a key enzyme in the biosynthesis of galactocerebroside, the most abundant glycosphingolipid in the myelin sheath. An 8 kb fragment upstream from the transcription initiation site of CGT gene was isolated from a human genomic DNA library. Primer extension analysis revealed a single transcription initiation site 329 bp upstream from the ATG start codon. Neither a consensus TATA nor a CCAAT box was identified in the proximity to the transcription start site; however, this region contains a high GC content and multiple putative regulatory elements. To investigate the transcriptional regulation of CGT, a series of 5' deletion constructs of the 5'-flanking region were generated and cloned upstream from the luciferase reporter gene. By comparing promoter activity in the human oligodendroglioma (HOG) and human neuroblastoma (LAN-5) cell lines, we found that the CGT promoter functions in a cell type-specific manner. Three positive cis-acting regulatory regions were identified, including a proximal region at -292/-256 which contains the potential binding sites for known transcription factors (TFs) such as Ets and SP1 (GC box), a distal region at -747/-688 comprising a number of binding sites such as the ERE half-site, NF1-like, TGGCA-BP, and CRE, and a third positive cis-acting region distally localized at -1325/-1083 consisting of binding sites for TFs such as nitrogen regulatory, TCF-1, TGGCA-BP, NF-IL6, CF1, bHLH, NF1-like, GATA, and gamma-IRE. A negative cis-acting domain localized in a far distal region at -1594/-1326 was also identified. Our results suggest the presence of both positive and negative cis-regulatory regions essential for the cell-specific expression in the TATA-less promoter of the human CGT gene.

Organizational requirements of the SaeR binding sites for a functional P1 promoter of the sae operon in Staphylococcus aureus.

PubMed

Cho, Hoonsik; Jeong, Do-Won; Li, Chunling; Bae, Taeok

2012-06-01

In Staphylococcus aureus, the SaeRS two-component system controls the expression of multiple virulence factors. Of the two promoters in the sae operon, P1 is autoinduced and has two binding sites for the response regulator SaeR. In this study, we examined the organizational requirements of the SaeR binding sites in P1 for transcription activation. Mutational studies showed that both binding sites are essential for binding to phosphorylated SaeR (P-SaeR) and transcription activation. When the 21-bp distance between the centers of the two SaeR binding sites was altered to 26 bp, 31 bp, 36 bp, or 41 bp, only the 31-bp mutant retained approximately 40% of the original promoter activity. When the -1-bp spacing (i.e.,1-bp overlap) between the primary SaeR binding site and the -35 promoter region was altered, all mutant P1 promoters failed to initiate transcription; however, when the first nucleotide of the -35 region was changed from A to T, the mutants with 0-bp or 22-bp spacing showed detectable promoter activity. Although P-SaeR was essential for the binding of RNA polymerase to P1, it was not essential for the binding of the enzyme to the alpha-hemolysin promoter. When the nonoptimal spacing between promoter elements in P1 or the coagulase promoter was altered to the optimal spacing of 17 bp, both promoters failed to initiate transcription. These results suggest that SaeR binding sites are under rather strict organizational restrictions and provide clues for understanding the molecular mechanism of sae-mediated transcription activation.

The impact of embedding multiple modes of representation on student construction of chemistry knowledge

NASA Astrophysics Data System (ADS)

McDermott, Mark Andrew

2009-12-01

This study was designed to examine the impact of embedding multiple modes of representing science information on student conceptual understanding in science. Multiple representations refer to utilizing charts, graphs, diagrams, and other types of representations to communicate scientific information. This study investigated the impact of encouraging students to embed or integrate the multiple modes with text in end of unit writing-to-learn activities. A quasi-experimental design with four separate sites consisting of intact chemistry classes taught by different teachers at each site was utilized. At each site, approximately half of the classes were designated treatment classes and students in these classes participated in activities designed to encourage strategies to embed multiple modes within text in student writing. The control classes did not participate in these activities. All classes participated in identical end of unit writing tasks in which they were required to use at least one mode other than text, followed by identical end of unit assessments. This progression was then repeated for a second consecutive unit of study. Analysis of quantitative data indicated that in several cases, treatment classes significantly outperformed control classes both on measures of embeddedness in writing and on end of unit assessment measures. In addition, analysis at the level of individual students indicated significant positive correlations in many cases between measures of student embeddedness in writing and student performance on end of unit assessments. Three factors emerged as critical in increasing the likelihood of benefit for students from these types of activities. First, the level of teacher implementation and emphasis on the embeddedness lessons was linked to the possibility of conceptual benefit. Secondly, students participating in two consecutive lessons appeared to receive greater benefit during the second unit, inferring a cumulative benefit. Finally, differential impact of the degree of embeddedness on student performance was noted based on student's level of science ability prior to the initiation of study procedures.

How MCM loading and spreading specify eukaryotic DNA replication initiation sites.

PubMed

Hyrien, Olivier

2016-01-01

DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb) non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs), the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC), they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes.

Emergence of dominant initiation sites for interictal spikes in rat neocortex

PubMed Central

Vitantonio, Daniel; Xu, Weifeng; Geng, Xinling; Wolff, Brian S.; Takagaki, Kentaroh; Motamedi, Gholam K.

2015-01-01

Neuronal populations with unbalanced inhibition can generate interictal spikes (ISs), where each IS starts from a small initiation site and then spreads activation across a larger area. We used in vivo voltage-sensitive dye imaging to map the initiation site of ISs in rat visual cortex disinhibited by epidural application of bicuculline methiodide. Immediately after the application of bicuculline, the IS initiation sites were widely distributed over the entire disinhibited area. After ∼10 min, a small number of sites became “dominant” and initiated the majority of the ISs throughout the course of imaging. Such domination also occurred in cortical slices, which lack long-range connections between the cortex and subcortical structures. This domination of IS initiation sites may allow timing-related plasticity mechanisms to provide a spatial organization where connections projecting outward from the dominant initiation site become strengthened. Understanding the spatiotemporal organization of IS initiation sites may contribute to our understanding of epileptogenesis in its very early stages, because a dominant IS initiation site with strengthened outward connectivity may ultimately develop into a seizure focus. PMID:26445866

Identification of Geomorphic Conditions Favoring Preservation of Multiple Individual Displacements Across Transform Faults

NASA Astrophysics Data System (ADS)

Williams, P. L.; Phillips, D. A.; Bowles-Martinez, E.; Masana, E.; Stepancikova, P.

2010-12-01

Terrestrial and airborne LiDAR data, and low altitude aerial photography have been utilized in conjunction with field work to identify and map single and multiple-event stream-offsets along all strands of the San Andreas fault in the Coachella Valley. Goals of the work are characterizing the range of displacements associated with the fault’s prehistoric surface ruptures, evaluating patterns of along-fault displacement, and disclosing processes associated with the prominent Banning-Mission Creek fault junction. Preservation offsets is associated with landscape conditions including: (1) well-confined and widely spaced source streams up-slope of the fault; (2) persistent geomorphic surfaces below the fault; (3) slope directions oriented approximately perpendicular to the fault. Notably, a pair of multiple-event offset sites have been recognized in coarse fan deposits below the Mission Creek fault near 1000 Palms oasis. Each of these sites is associated with a single source drainage oriented approximately perpendicular to the fault, and preserves a record of individual fault displacements affecting the southern portion of the Mission Creek branch of the San Andreas fault. The two sites individually record long (>10 event) slip-per-event histories. Documentation of the sites indicates a prevalence of moderate displacements and a small number of large offsets. This is consistent with evidence developed in systematic mapping of individual and multiple event stream offsets in the area extending 70 km south to Durmid Hill. Challenges to site interpretation include the presence of closely spaced en echelon fault branches and indications of stream avulsion in the area of the modern fault crossing. Conversely, strong bar and swale topography produce high quality offset indicators that can be identified across en echelon branches in most cases. To accomplish the detailed mapping needed to fully recover the complex yet well-preserved geomorphic features under investigation, a program of terrestrial laser scanning (TLS) was conducted at the 1000 Palms oasis stream offset sites. Data products and map interpretations will be presented along with initial applications of the study to characterizing San Andreas fault rupture hazard. Continuing work will seek to more fully populate the dataset of larger offsets, evaluate means to objectively date the larger offsets, and, as completely as possible, to characterize magnitudes of past surface ruptures of the San Andreas fault in the Coachella Valley.

Characteristics of pediatric multiple sclerosis: The Turkish pediatric multiple sclerosis database.

PubMed

Yılmaz, Ünsal; Anlar, Banu; Gücüyener, Kıvılcım

2017-11-01

To document the clinical and paraclinical features of pediatric multiple sclerosis (MS) in Turkey. Data of MS patients with onset before age 18 years (n = 193) were collected from 27 pediatric neurology centers throughout Turkey. Earlier-onset (<12 years) and later-onset (≥12 years) groups were compared. There were 123 (63.7%) girls and 70 (36.3%) boys aged 4-17 years, median 14 years at disease onset. Family history of MS was 6.5%. The first presentation was polysymptomatic in 55.4% of patients, with brainstem syndromes (50.3%), sensory disturbances (44%), motor symptoms (33.2%), and optic neuritis (26.4%) as common initial manifestations. Nineteen children had facial paralysis and 10 had epileptic seizures at first attack; 21 (11%) were initially diagnosed with acute disseminated encephalomyelitis (ADEM). Oligoclonal bands were identified in 68% of patients. Magnetic resonance imaging revealed periventricular (96%), cortical/juxtacortical (64.2%), brainstem (63%), cerebellum (51.4%), and spinal cord (67%) involvement. Visual evoked potentials (VEP) were abnormal in 52%; serum 25-hydroxyvitamin D levels were low in 68.5% of patients. The earlier-onset group had a higher rate of infection/vaccination preceding initial attack, initial diagnosis of ADEM, longer interval between first 2 attacks, and more disability accumulating in the first 3 years of the disease. Brainstem and cerebellum are common sites of clinical and radiological involvement in pediatric-onset MS. VEP abnormalities are frequent even in patients without history of optic neuropathy. Vitamin D status does not appear to affect the course in early disease. MS beginning before 12 years of age has certain characteristics in history and course. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The genomic structure of the human UFO receptor.

PubMed

Schulz, A S; Schleithoff, L; Faust, M; Bartram, C R; Janssen, J W

1993-02-01

Using a DNA transfection-tumorigenicity assay we have recently identified the UFO oncogene. It encodes a tyrosine kinase receptor characterized by the juxtaposition of two immunoglobulin-like and two fibronectin type III repeats in its extracellular domain. Here we describe the genomic organization of the human UFO locus. The UFO receptor is encoded by 20 exons that are distributed over a region of 44 kb. Different isoforms of UFO mRNA are generated by alternative splicing of exon 10 and differential usage of two imperfect polyadenylation sites resulting in the presence or absence of 1.5-kb 3' untranslated sequences. Primer extension and S1 nuclease analyses revealed multiple transcriptional initiation sites including a major site 169 bp upstream of the translation start site. The promoter region is GC rich, lacks TATA and CAAT boxes, but contains potential recognition sites for a variety of trans-acting factors, including Sp1, AP-2 and the cyclic AMP response element-binding protein. Proto-UFO and its oncogenic counterpart exhibit identical cDNA and promoter regions sequences. Possible modes of UFO activation are discussed.

Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site.

PubMed

Means, A L; Farnham, P J

1990-02-01

We have identified a sequence element that specifies the position of transcription initiation for the dihydrofolate reductase gene. Unlike the functionally analogous TATA box that directs RNA polymerase II to initiate transcription 30 nucleotides downstream, the positioning element of the dihydrofolate reductase promoter is located directly at the site of transcription initiation. By using DNase I footprint analysis, we have shown that a protein binds to this initiator element. Transcription initiated at the dihydrofolate reductase initiator element when 28 nucleotides were inserted between it and all other upstream sequences, or when it was placed on either side of the DNA helix, suggesting that there is no strict spatial requirement between the initiator and an upstream element. Although neither a single Sp1-binding site nor a single initiator element was sufficient for transcriptional activity, the combination of one Sp1-binding site and the dihydrofolate reductase initiator element cloned into a plasmid vector resulted in transcription starting at the initiator element. We have also shown that the simian virus 40 late major initiation site has striking sequence homology to the dihydrofolate reductase initiation site and that the same, or a similar, protein binds to both sites. Examination of the sequences at other RNA polymerase II initiation sites suggests that we have identified an element that is important in the transcription of other housekeeping genes. We have thus named the protein that binds to the initiator element HIP1 (Housekeeping Initiator Protein 1).

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Constraints on core-collapse supernova progenitors from explosion site integral field spectroscopy

NASA Astrophysics Data System (ADS)

Kuncarayakti, H.; Anderson, J. P.; Galbany, L.; Maeda, K.; Hamuy, M.; Aldering, G.; Arimoto, N.; Doi, M.; Morokuma, T.; Usuda, T.

2018-05-01

Context. Observationally, supernovae (SNe) are divided into subclasses according to their distinct characteristics. This diversity naturally reflects the diversity in the progenitor stars. It is not entirely clear, however, how different evolutionary paths leading massive stars to become an SN are governed by fundamental parameters such as progenitor initial mass and metallicity. Aims: This paper places constraints on progenitor initial mass and metallicity in distinct core-collapse SN subclasses through a study of the parent stellar populations at the explosion sites. Methods: Integral field spectroscopy (IFS) of 83 nearby SN explosion sites with a median distance of 18 Mpc has been collected and analysed, enabling detection and spectral extraction of the parent stellar population of SN progenitors. From the parent stellar population spectrum, the initial mass and metallicity of the coeval progenitor are derived by means of comparison to simple stellar population models and strong-line methods. Additionally, near-infrared IFS was employed to characterise the star formation history at the explosion sites. Results: No significant metallicity differences are observed among distinct SN types. The typical progenitor mass is found to be highest for SN type Ic, followed by type Ib, then types IIb and II. Type IIn is the least associated with young stellar populations and thus massive progenitors. However, statistically significant differences in progenitor initial mass are observed only when comparing SNe IIn with other subclasses. Stripped-envelope SN progenitors with initial mass estimates lower than 25 M⊙ are found; they are thought to be the result of binary progenitors. Confirming previous studies, these results support the notion that core-collapse SN progenitors cannot arise from single-star channels only, and both single and binary channels are at play in the production of core-collapse SNe. Near-infrared IFS suggests that multiple stellar populations with different ages may be present in some of the SN sites. As a consequence, there could be a non-negligible amount of contamination from old populations, and therefore the individual age estimates are effectively lower limits. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programmes 089.D-0367, 091.D-0482, 093.D-0318, 094.D-0290, and 095.D-0172

15 CFR 921.33 - Boundary changes, amendments to the management plan, and addition of multiple-site components.

Code of Federal Regulations, 2010 CFR

2010-01-01

... management plan, and addition of multiple-site components. 921.33 Section 921.33 Commerce and Foreign Trade... management plan, and addition of multiple-site components. (a) Changes in the boundary of a Reserve and major... management plan shall address goals and objectives for all components of the multi-site Reserve and the...

G-actin provides substrate-specificity to eukaryotic initiation factor 2α holophosphatases

PubMed Central

Chen, Ruming; Rato, Cláudia; Yan, Yahui; Crespillo-Casado, Ana; Clarke, Hanna J; Harding, Heather P; Marciniak, Stefan J; Read, Randy J; Ron, David

2015-01-01

Dephosphorylation of eukaryotic translation initiation factor 2a (eIF2a) restores protein synthesis at the waning of stress responses and requires a PP1 catalytic subunit and a regulatory subunit, PPP1R15A/GADD34 or PPP1R15B/CReP. Surprisingly, PPP1R15-PP1 binary complexes reconstituted in vitro lacked substrate selectivity. However, selectivity was restored by crude cell lysate or purified G-actin, which joined PPP1R15-PP1 to form a stable ternary complex. In crystal structures of the non-selective PPP1R15B-PP1G complex, the functional core of PPP1R15 made multiple surface contacts with PP1G, but at a distance from the active site, whereas in the substrate-selective ternary complex, actin contributes to one face of a platform encompassing the active site. Computational docking of the N-terminal lobe of eIF2a at this platform placed phosphorylated serine 51 near the active site. Mutagenesis of predicted surface-contacting residues enfeebled dephosphorylation, suggesting that avidity for the substrate plays an important role in imparting specificity on the PPP1R15B-PP1G-actin ternary complex. DOI: http://dx.doi.org/10.7554/eLife.04871.001 PMID:25774600

Recognition of the Xenopus ribosomal core promoter by the transcription factor xUBF involves multiple HMG box domains and leads to an xUBF interdomain interaction.

PubMed

Leblanc, B; Read, C; Moss, T

1993-02-01

The interaction of the ribosomal transcription factor xUBF with the RNA polymerase I core promoter of Xenopus laevis has been studied both at the DNA and protein levels. It is shown that a single xUBF-DNA complex forms over the 40S initiation site (+1) and involves at least the DNA sequences between -20 and +60 bp. DNA sequences upstream of +10 and downstream of +18 are each sufficient to direct complex formation independently. HMG box 1 of xUBF independently recognizes the sequences -20 to -1 and +1 to +22 and the addition of the N-terminal dimerization domain to HMG box 1 stabilizes its interaction with these sequences approximately 10-fold. HMG boxes 2/3 interact with the DNA downstream of +22 and can independently position xUBF across the initiation site. The C-terminal segment of xUBF, HMG boxes 4, 5 or the acidic domain, directly or indirectly interact with HMG box 1, making the core promoter sequences between -11 and -15 hypersensitive to DNase. This interaction also requires the DNA sequences between +17 and +32, i.e. the HMG box 2/3 binding site. The data suggest extensive folding of the core promoter within the xUBF complex.

Six Degree-of-Freedom Entry Dispersion Analysis for the METEOR Recovery Module

NASA Technical Reports Server (NTRS)

Desai, Prasun N.; Braun, Robert D.; Powell, Richard W.; Engelund, Walter C.; Tartabini, Paul V.

1996-01-01

The present study performs a six degree-of-freedom entry dispersion analysis for the Multiple Experiment Transporter to Earth Orbit and Return (METEOR) mission. METEOR offered the capability of flying a recoverable science package in a microgravity environment. However, since the Recovery Module has no active control system, an accurate determination of the splashdown position is difficult because no opportunity exists to remove any errors. Hence, uncertainties in the initial conditions prior to deorbit burn initiation, during deorbit burn and exo-atmospheric coast phases, and during atmospheric flight impact the splashdown location. This investigation was undertaken to quantify the impact of the various exo-atmospheric and atmospheric uncertainties. Additionally, a Monte-Carlo analysis was performed to statistically assess the splashdown dispersion footprint caused by the multiple mission uncertainties. The Monte-Carlo analysis showed that a 3-sigma splashdown dispersion footprint with axes of 43.3 nm (long), -33.5 nm (short), and 10.0 nm (crossrange) can be constructed. A 58% probability exists that the Recovery Module will overshoot the nominal splashdown site.

Timing of Chemotherapy After MammoSite Radiation Therapy System Breast Brachytherapy: Analysis of the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial

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

Haffty, Bruce G.; Vicini, Frank A.; Beitsch, Peter

2008-12-01

Purpose: To evaluate cosmetic outcome and radiation recall in the American Society of Breast Surgeons registry trial, as a function of the interval between accelerated partial breast irradiation (APBI) and initiation of chemotherapy (CTX). Methods and Materials: A total of 1440 patients at 97 institutions participated in this trial. After lumpectomy for early-stage breast cancer, patients received APBI (34 Gy in 10 fractions) with MammoSite RTS brachytherapy. A total of 148 patients received CTX within 90 days of APBI. Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good or fair/poor. Results: Chemotherapy was initiated at a meanmore » of 3.9 weeks after the final MammoSite procedure and was administered {<=}3 weeks after APBI in 54 patients (36%) and >3 weeks after APBI in 94 patients (64%). The early and delayed groups were well balanced with respect to multiple factors that may impact on cosmetic outcome. There was a superior cosmetic outcome in those receiving chemotherapy >3 weeks after APBI (excellent/good in 72.2% at {<=}3 weeks vs. excellent/good in 93.8% at >3 weeks; p = 0.01). Radiation recall in those receiving CTX at {<=}3 weeks was 9 of 50 (18%), compared with 6 of 81(7.4%) in those receiving chemotherapy at >3 weeks (p = 0.09). Conclusion: The majority of patients receiving CTX after APBI have excellent/good cosmetic outcomes, with a low rate of radiation recall. Chemotherapy initiated >3 weeks after the final MammoSite procedure seems to be associated with a better cosmetic outcome and lower rate of radiation recall. An excellent/good cosmetic outcome in patients receiving CTX after 3 weeks was similar to the cosmetic outcome of the overall patient population who did not receive CTX.« less

The structure of a protein primer-polymerase complex in the initiation of genome replication.

PubMed

Ferrer-Orta, Cristina; Arias, Armando; Agudo, Rubén; Pérez-Luque, Rosa; Escarmís, Cristina; Domingo, Esteban; Verdaguer, Nuria

2006-02-22

Picornavirus RNA replication is initiated by the covalent attachment of a UMP molecule to the hydroxyl group of a tyrosine in the terminal protein VPg. This reaction is carried out by the viral RNA-dependent RNA polymerase (3D). Here, we report the X-ray structure of two complexes between foot-and-mouth disease virus 3D, VPg1, the substrate UTP and divalent cations, in the absence and in the presence of an oligoadenylate of 10 residues. In both complexes, VPg fits the RNA binding cleft of the polymerase and projects the key residue Tyr3 into the active site of 3D. This is achieved by multiple interactions with residues of motif F and helix alpha8 of the fingers domain and helix alpha13 of the thumb domain of the polymerase. The complex obtained in the presence of the oligoadenylate showed the product of the VPg uridylylation (VPg-UMP). Two metal ions and the catalytic aspartic acids of the polymerase active site, together with the basic residues of motif F, have been identified as participating in the priming reaction.

Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

PubMed

Grarup, J; Rappoport, C; Engen, N W; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, M J

2015-04-01

The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem-solving. © 2015 British HIV Association.

Characterization of the human gene (TBXAS1) encoding thromboxane synthase.

PubMed

Miyata, A; Yokoyama, C; Ihara, H; Bandoh, S; Takeda, O; Takahashi, E; Tanabe, T

1994-09-01

The gene encoding human thromboxane synthase (TBXAS1) was isolated from a human EMBL3 genomic library using human platelet thromboxane synthase cDNA as a probe. Nucleotide sequencing revealed that the human thromboxane synthase gene spans more than 75 kb and consists of 13 exons and 12 introns, of which the splice donor and acceptor sites conform to the GT/AG rule. The exon-intron boundaries of the thromboxane synthase gene were similar to those of the human cytochrome P450 nifedipine oxidase gene (CYP3A4) except for introns 9 and 10, although the primary sequences of these enzymes exhibited 35.8% identity each other. The 1.2-kb of the 5'-flanking region sequence contained potential binding sites for several transcription factors (AP-1, AP-2, GATA-1, CCAAT box, xenobiotic-response element, PEA-3, LF-A1, myb, basic transcription element and cAMP-response element). Primer-extension analysis indicated the multiple transcription-start sites, and the major start site was identified as an adenine residue located 142 bases upstream of the translation-initiation site. However, neither a typical TATA box nor a typical CAAT box is found within the 100-b upstream of the translation-initiation site. Southern-blot analysis revealed the presence of one copy of the thromboxane synthase gene per haploid genome. Furthermore, a fluorescence in situ hybridization study revealed that the human gene for thromboxane synthase is localized to band q33-q34 of the long arm of chromosome 7. A tissue-distribution study demonstrated that thromboxane synthase mRNA is widely expressed in human tissues and is particularly abundant in peripheral blood leukocyte, spleen, lung and liver. The low but significant levels of mRNA were observed in kidney, placenta and thymus.

Challenges, successes and patterns of enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial

PubMed Central

Rappoport, C; Engen, NW; Carey, C; Hudson, F; Denning, E; Sharma, S; Florence, E; Vjecha, MJ

2015-01-01

Objectives The aim of this report is to describe the challenges, successes and patterns of enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. Methods START is a collaboration of many partners with central coordination provided by the protocol team, the statistical and data management centre (SDMC), the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) network leadership, international coordinating centres and site coordinating centres. The SDMC prepared reports on study accrual, baseline characteristics and site performance that allowed monitoring of enrolment and data quality and helped to ensure the successful enrolment of this large international trial. We describe the pattern of enrolment and challenges faced during the enrolment period of the trial. Results An initial pilot phase began in April 2009 and established feasibility of accrual at 101 sites. In August 2010, funding approval for an expanded definitive phase led to the successful accrual of 4688 participants from 215 sites in 35 countries by December 2013. Challenges to accrual included regulatory delays (e.g. national/local ethics approval and drug importation approval) and logistical obstacles (e.g. execution of contracts with pharmaceutical companies, setting up of a central drug repository and translation of participant materials). The personal engagement of investigators, strong central study coordination, and frequent and transparent communication with site investigators, community members and participants were key contributing factors to this success. Conclusions Accrual into START was completed in a timely fashion despite multiple challenges. This success was attributable to the efforts of site investigators committed to maintaining study equipoise, transparent and responsive study coordination, and community involvement in problem‐solving. PMID:25711319

Variation in body mass dynamics among sites in Black Brant Branta bernicla nigricans supports adaptivity of mass loss during moult

USGS Publications Warehouse

Fondell, Thomas F.; Flint, Paul L.; Schmutz, Joel A.; Schamber, Jason L.; Nicolai, Christopher A.

2013-01-01

Birds employ varying strategies to accommodate the energetic demands of moult, one important example being changes in body mass. To understand better their physiological and ecological significance, we tested three hypotheses concerning body mass dynamics during moult. We studied Black Brant in 2006 and 2007 moulting at three sites in Alaska which varied in food availability, breeding status and whether geese undertook a moult migration. First we predicted that if mass loss during moult were simply the result of inadequate food resources then mass loss would be highest where food was least available. Secondly, we predicted that if mass loss during moult were adaptive, allowing birds to reduce activity during moult, then birds would gain mass prior to moult where feeding conditions allowed and mass loss would be positively related to mass at moult initiation. Thirdly, we predicted that if mass loss during moult were adaptive, allowing birds to regain flight sooner, then across sites and groups, mass at the end of the flightless period would converge on a theoretical optimum, i.e. the mass that permits the earliest possible return to flight. Mass loss was greatest where food was most available and thus our results did not support the prediction that mass loss resulted from inadequate food availability. Mass at moult initiation was positively related to both food availability and mass loss. In addition, among sites and years, variation in mass was high at moult initiation but greatly reduced at the end of the flightless period, appearing to converge. Thus, our results supported multiple predictions that mass loss during moult was adaptive and that the optimal moulting strategy was to gain mass prior to the flightless period, then through behavioural modifications use these body reserves to reduce activity and in so doing also reduce wing loading. Geese that undertook a moult migration initiated moult at the highest mass, indicating that they were more than able to compensate for the energetic cost of the migration. Because Brant frequently change moult sites between years in relation to breeding success, the site-specific variation in body mass dynamics we observed suggests individual plasticity in moult body mass dynamics.

Training and support to improve ICD coding quality: A controlled before-and-after impact evaluation.

PubMed

Dyers, Robin; Ward, Grant; Du Plooy, Shane; Fourie, Stephanus; Evans, Juliet; Mahomed, Hassan

2017-05-24

The proposed National Health Insurance policy for South Africa (SA) requires hospitals to maintain high-quality International Statistical Classification of Diseases (ICD) codes for patient records. While considerable strides had been made to improve ICD coding coverage by digitising the discharge process in the Western Cape Province, further intervention was required to improve data quality. The aim of this controlled before-and-after study was to evaluate the impact of a clinician training and support initiative to improve ICD coding quality. To compare ICD coding quality between two central hospitals in the Western Cape before and after the implementation of a training and support initiative for clinicians at one of the sites. The difference in differences in data quality between the intervention site and the control site was calculated. Multiple logistic regression was also used to determine the odds of data quality improvement after the intervention and to adjust for potential differences between the groups. The intervention had a positive impact of 38.0% on ICD coding completeness over and above changes that occurred at the control site. Relative to the baseline, patient records at the intervention site had a 6.6 (95% confidence interval 3.5 - 16.2) adjusted odds ratio of having a complete set of ICD codes for an admission episode after the introduction of the training and support package. The findings on impact on ICD coding accuracy were not significant. There is sufficient pragmatic evidence that a training and support package will have a considerable positive impact on ICD coding completeness in the SA setting.

MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development.

PubMed

Lu, Cecilia S; Zhai, Bo; Mauss, Alex; Landgraf, Matthias; Gygi, Stephen; Van Vactor, David

2014-09-26

Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins.

MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development

PubMed Central

Lu, Cecilia S.; Zhai, Bo; Mauss, Alex; Landgraf, Matthias; Gygi, Stephen; Van Vactor, David

2014-01-01

Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development in Drosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labelling in vivo and comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins. PMID:25135978

75 FR 41639 - Availability of Grant Funds for Fiscal Year 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

...The National Oceanic and Atmospheric Administration publishes this notice to provide the general public with a consolidated source of program and application information related to its competitive grant and cooperative agreement award offerings for fiscal year (FY) 2011. This Omnibus notice is designed to replace the multiple Federal Register notices that traditionally advertised the availability of NOAA's discretionary funds for its various programs. It should be noted that additional program initiatives may be announced through subsequent Federal Register notices. All announcements will also be available through the Grants.gov Web site.

Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay.

PubMed

Salim, Elsayed I

2010-09-01

Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered. The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation.

Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay

PubMed Central

SALIM, ELSAYED I.

2010-01-01

Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered. The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation. PMID:22966405

Phosphorylation is required for the pathogen defense function of the Arabidopsis PEN3 ABC transporter.

PubMed

Underwood, William; Somerville, Shauna C

2017-10-03

The Arabidopsis PEN3 ABC transporter accumulates at sites of pathogen detection, where it is involved in defense against a number of pathogens. Perception of PAMPs by pattern recognition receptors initiates recruitment of PEN3 and also leads to PEN3 phosphorylation at multiple amino acid residues. Whether PAMP-induced phosphorylation of PEN3 is important for its defense function or focal recruitment has not been addressed. In this study, we evaluated the role of PEN3 phosphorylation in modulating the localization and defense function of the transporter. We report that PEN3 phosphorylation is critical for its function in defense, but dispensable for recruitment to powdery mildew penetration sites. These results indicate that PAMP-induced phosphorylation is likely to regulate the transport activity of PEN3.

Method for producing damage resistant optics

DOEpatents

Hackel, Lloyd A.; Burnham, Alan K.; Penetrante, Bernardino M.; Brusasco, Raymond M.; Wegner, Paul J.; Hrubesh, Lawrence W.; Kozlowski, Mark R.; Feit, Michael D.

2003-01-01

The present invention provides a system that mitigates the growth of surface damage in an optic. Damage to the optic is minimally initiated. In an embodiment of the invention, damage sites in the optic are initiated, located, and then treated to stop the growth of the damage sites. The step of initiating damage sites in the optic includes a scan of the optic using a laser to initiate defects. The exact positions of the initiated sites are identified. A mitigation process is performed that locally or globally removes the cause of subsequent growth of the damaged sites.

How MCM loading and spreading specify eukaryotic DNA replication initiation sites

PubMed Central

Hyrien, Olivier

2016-01-01

DNA replication origins strikingly differ between eukaryotic species and cell types. Origins are localized and can be highly efficient in budding yeast, are randomly located in early fly and frog embryos, which do not transcribe their genomes, and are clustered in broad (10-100 kb) non-transcribed zones, frequently abutting transcribed genes, in mammalian cells. Nonetheless, in all cases, origins are established during the G1-phase of the cell cycle by the loading of double hexamers of the Mcm 2-7 proteins (MCM DHs), the core of the replicative helicase. MCM DH activation in S-phase leads to origin unwinding, polymerase recruitment, and initiation of bidirectional DNA synthesis. Although MCM DHs are initially loaded at sites defined by the binding of the origin recognition complex (ORC), they ultimately bind chromatin in much greater numbers than ORC and only a fraction are activated in any one S-phase. Data suggest that the multiplicity and functional redundancy of MCM DHs provide robustness to the replication process and affect replication time and that MCM DHs can slide along the DNA and spread over large distances around the ORC. Recent studies further show that MCM DHs are displaced along the DNA by collision with transcription complexes but remain functional for initiation after displacement. Therefore, eukaryotic DNA replication relies on intrinsically mobile and flexible origins, a strategy fundamentally different from bacteria but conserved from yeast to human. These properties of MCM DHs likely contribute to the establishment of broad, intergenic replication initiation zones in higher eukaryotes. PMID:27635237

Local and systemic tumor immune dynamics

NASA Astrophysics Data System (ADS)

Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

Oldest known dinosaurian nesting site and reproductive biology of the Early Jurassic sauropodomorph Massospondylus

PubMed Central

Reisz, Robert R.; Evans, David C.; Roberts, Eric M.; Sues, Hans-Dieter; Yates, Adam M.

2012-01-01

The extensive Early Jurassic continental strata of southern Africa have yielded an exceptional record of dinosaurs that includes scores of partial to complete skeletons of the sauropodomorph Massospondylus, ranging from embryos to large adults. In 1976 an incomplete egg clutch including in ovo embryos of this dinosaur, the oldest known example in the fossil record, was collected from a road-cut talus, but its exact provenance was uncertain. An excavation program at the site started in 2006 has yielded multiple in situ egg clutches, documenting the oldest known dinosaurian nesting site, predating other similar sites by more than 100 million years. The presence of numerous clutches of eggs, some of which contain embryonic remains, in at least four distinct horizons within a small area, provides the earliest known evidence of complex reproductive behavior including site fidelity and colonial nesting in a terrestrial vertebrate. Thus, fossil and sedimentological evidence from this nesting site provides empirical data on reproductive strategies in early dinosaurs. A temporally calibrated optimization of dinosaurian reproductive biology not only demonstrates the primary significance of the Massospondylus nesting site, but also provides additional insights into the initial stages of the evolutionary history of dinosaurs, including evidence that deposition of eggs in a tightly organized single layer in a nest evolved independently from brooding. PMID:22308330

The Joint Experiment for Crop Assessment and Monitoring (JECAM) Initiative: Developing methods and best practices for global agricultural monitoring

NASA Astrophysics Data System (ADS)

Champagne, C.; Jarvis, I.; Defourny, P.; Davidson, A.

2014-12-01

Agricultural systems differ significantly throughout the world, making a 'one size fits all' approach to remote sensing and monitoring of agricultural landscapes problematic. The Joint Experiment for Crop Assessment and Monitoring (JECAM) was established in 2009 to bring together the global scientific community to work towards a set of best practices and recommendations for using earth observation data to map, monitor and report on agricultural productivity globally across an array of diverse agricultural systems. These methods form the research and development component of the Group on Earth Observation Global Agricultural Monitoring (GEOGLAM) initiative to harmonize global monitoring efforts and increase market transparency. The JECAM initiative brings together researchers from a large number of globally distributed, well monitored agricultural test sites that cover a range of crop types, cropping systems and climate regimes. Each test site works independently as well as together across multiple sites to test methods, sensors and field data collection techniques to derive key agricultural parameters, including crop type, crop condition, crop yield and soil moisture. The outcome of this project will be a set of best practices that cover the range of remote sensing monitoring and reporting needs, including satellite data acquisition, pre-processing techniques, information retrieval and ground data validation. These outcomes provide the research and development foundation for GEOGLAM and will help to inform the development of the GEOGLAM "system of systems" for global agricultural monitoring. The outcomes of the 2014 JECAM science meeting will be discussed as well as examples of methods being developed by JECAM scientists.

Test-retest and between-site reliability in a multicenter fMRI study.

PubMed

Friedman, Lee; Stern, Hal; Brown, Gregory G; Mathalon, Daniel H; Turner, Jessica; Glover, Gary H; Gollub, Randy L; Lauriello, John; Lim, Kelvin O; Cannon, Tyrone; Greve, Douglas N; Bockholt, Henry Jeremy; Belger, Aysenil; Mueller, Bryon; Doty, Michael J; He, Jianchun; Wells, William; Smyth, Padhraic; Pieper, Steve; Kim, Seyoung; Kubicki, Marek; Vangel, Mark; Potkin, Steven G

2008-08-01

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

Engineering Evaluation of International Low Impact Docking System Latch Hooks

NASA Technical Reports Server (NTRS)

Martinez, J.; Patin, R.; Figert, J.

2013-01-01

The international Low Impact Docking System (iLIDS) provides a structural arrangement that allows for visiting vehicles to dock with the International Space Station (ISS) (Fig 1). The iLIDS docking units are mechanically joined together by a series of active and passive latch hooks. In order to preserve docking capability at the existing Russian docking interfaces, the iLIDS latch hooks are required to conform to the existing Russian design. The latch hooks are classified as being fail-safe. Since the latch hooks are fail-safe, the hooks are not fracture critical and a fatigue based service life assessment will satisfy the structural integrity requirements. Constant amplitude fatigue testing to failure on four sets of active/passive iLIDS latch hooks was performed at load magnitudes of 10, 11, and 12 kips. Failure analysis of the hook fatigue failures identified multi-site fatigue initiation that was effectively centered about the hook mid-plane (consistent with the 3D model results). The fatigue crack initiation distribution implies that the fatigue damage accumulation effectively results in a very low aspect ratio surface crack (which can be simulated as thru-thickness crack). Fatigue damage progression resulted in numerous close proximity fatigue crack initiation sites. It was not possible to determine if fatigue crack coalescence occurs during cyclic loading or as result of the fast fracture response. The presence of multiple fatigue crack initiation sites on different planes will result in the formation of ratchet marks as the cracks coalesce. Once the stable fatigue crack becomes unstable and the fast fracture advances across the remaining ligament and the plane stress condition at a free-surface will result in failure along a 45 deg. shear plane (slant fracture) and the resulting inclined edge is called a shear lip. The hook thickness on the plane of fatigue crack initiation is 0.787". The distance between the shear lips on this plane was on the order of 0.48" and it was effectively centered about the mid-plane of the section. The numerous ratchet marks between the shear lips on the fracture initiation plane are indicative of multiple fatigue initiation sites within this region. The distribution of the fatigue damage about the centerline of the hook is consistent with the analytical results that demonstrate peak stress/strain response at the mid-plane that decreases in the direction of the hook outer surfaces. Scanning electron microscope images of the failed sections detected fatigue crack striations in close proximity to the free surface of the hook radius. These findings were documented at three locations on the fracture surface : 1) adjacent to the left shear lip, 2) adjacent to the right shear lip, and 3) near the centerline of the section. The features of the titanium fracture surface did not allow for a determination of a critical crack size via identification of the region where the fatigue crack propagation became unstable. The fracture based service life projections where benchmarked with strain-life analyses. The strainrange response in the hook radius was defined via the correlated finite element models and the modified method of universal slopes was incorporated to define the strain-life equation for the titanium alloy. The strain-life assessment confirmed that the fracture based projections were reasonable for the loading range of interest. Based upon the analysis and component level fatigue test data a preliminary service life capability for the iLIDS active and passive hooks of 2 lifetimes is projected (includes a scatter factor of 4).

Site Features

EPA Pesticide Factsheets

This dataset consists of various site features from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and were combined into one region-wide layer.

The nucleotide sequence of the putative transcription initiation site of a cloned ribosomal RNA gene of the mouse.

PubMed Central

Urano, Y; Kominami, R; Mishima, Y; Muramatsu, M

1980-01-01

Approximately one kilobase pairs surrounding and upstream the transcription initiation site of a cloned ribosomal DNA (rDNA) of the mouse were sequenced. The putative transcription initiation site was determined by two independent methods: one nuclease S1 protection and the other reverse transcriptase elongation mapping using isolated 45S ribosomal RNA precursor (45S RNA) and appropriate restriction fragments of rDNA. Both methods gave an identical result; 45S RNA had a structure starting from ACTCTTAG---. Characteristically, mouse rDNA had many T clusters (greater than or equal to 5) upstream the initiation site, the longest being 21 consecutive T's. A pentadecanucleotide, TGCCTCCCGAGTGCA, appeared twice within 260 nucleotides upstream the putative initiation site. No such characteristic sequences were found downstream this site. Little similarity was found in the upstream of the transcription initiation site between the mouse, Xenopus laevis and Saccharomyces cerevisiae rDNA. Images PMID:6162156

Configuring a Graphical User Interface for Managing Local HYSPLIT Model Runs Through AWIPS

NASA Technical Reports Server (NTRS)

Wheeler, mark M.; Blottman, Peter F.; Sharp, David W.; Hoeth, Brian; VanSpeybroeck, Kurt M.

2009-01-01

Responding to incidents involving the release of harmful airborne pollutants is a continual challenge for Weather Forecast Offices in the National Weather Service. When such incidents occur, current protocol recommends forecaster-initiated requests of NOAA's Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model output through the National Centers of Environmental Prediction to obtain critical dispersion guidance. Individual requests are submitted manually through a secured web site, with desired multiple requests submitted in sequence, for the purpose of obtaining useful trajectory and concentration forecasts associated with the significant release of harmful chemical gases, radiation, wildfire smoke, etc., into local the atmosphere. To help manage the local HYSPLIT for both routine and emergency use, a graphical user interface was designed for operational efficiency. The interface allows forecasters to quickly determine the current HYSPLIT configuration for the list of predefined sites (e.g., fixed sites and floating sites), and to make any necessary adjustments to key parameters such as Input Model. Number of Forecast Hours, etc. When using the interface, forecasters will obtain desired output more confidently and without the danger of corrupting essential configuration files.

Initial insights into bacterial succession during human decomposition.

PubMed

Hyde, Embriette R; Haarmann, Daniel P; Petrosino, Joseph F; Lynne, Aaron M; Bucheli, Sibyl R

2015-05-01

Decomposition is a dynamic ecological process dependent upon many factors such as environment, climate, and bacterial, insect, and vertebrate activity in addition to intrinsic properties inherent to individual cadavers. Although largely attributed to microbial metabolism, very little is known about the bacterial basis of human decomposition. To assess the change in bacterial community structure through time, bacterial samples were collected from several sites across two cadavers placed outdoors to decompose and analyzed through 454 pyrosequencing and analysis of variable regions 3-5 of the bacterial 16S ribosomal RNA (16S rRNA) gene. Each cadaver was characterized by a change in bacterial community structure for all sites sampled as time, and decomposition, progressed. Bacteria community structure is variable at placement and before purge for all body sites. At bloat and purge and until tissues began to dehydrate or were removed, bacteria associated with flies, such as Ignatzschineria and Wohlfahrtimonas, were common. After dehydration and skeletonization, bacteria associated with soil, such as Acinetobacter, were common at most body sites sampled. However, more cadavers sampled through multiple seasons are necessary to assess major trends in bacterial succession.

Errant processing and structural alterations of genomes present in a varicella-zoster virus vaccine.

PubMed Central

Vlazny, D A; Hyman, R W

1985-01-01

Five minority populations of aberrant, varicella-zoster virus (VZV)-derived genomes were identified among the encapsidated DNAs obtained from the nuclear and cytoplasmic fractions of an in vitro infection initiated with a lyophilized sample of the BIKEN VZV vaccine (strain Oka). These were (i) VZV genomes, present within nuclear but not cytoplasmic viral capsids, which had been cleaved at a specific site within the short segment and which were, therefore, 3.15 megadaltons (approximately 4% of the VZV genome length) short of full length; (ii) highly deleted, repetitive VZV genomes which contained the errant cleavage site but not the usual VZV genome terminal sequences; (iii) VZV genomes into which multiples of 1 through 5 defective genome repeat units had been inserted into a homologous site; (iv) VZV genomes with additions of 0.1 or 0.18 megadaltons of DNA at both the terminal and internal ends of the short segment; and (v) VZV DNA which had lost the HindIII restriction site at map position 0.11. Images PMID:2993670

Multiple pathways from three types of sugar receptor sites to metabotropic transduction pathways of the blowfly: study by the whole cell-clamp experiments.

PubMed

Kan, Hideko; Kataoka-Shirasugi, Naoko; Amakawa, Taisaku

2011-09-01

Multiple pathways from three types of multiple receptor sites to three types of metabotropic signal transduction pathways were investigated in the whole cell-clamp experiments using isolated labellar sugar receptor neurons (cells) of the adult blowfly, Phormia regina. First, the concentration-response curves of three types of sweet taste components specialized to multiple receptor sites were obtained: sucrose for the pyranose sites (P-sites), fructose for the furanose sites (F-sites), and l-valine for the alkyl sites (R-sites). Next, the effects of inhibitors such as 2', 5'-dideoxyadenosine on adenylyl cyclase in the cAMP pathway, LY 83583 on guanylyl cyclase in the cGMP pathway, and U-73122 on phospholipase C in the IP₃ pathway were examined. The results showed that all of the inhibitors affected each specific target in the second-messenger transduction pathways. The obtained results verified that the P-site corresponded to the cAMP, the F-site to the cGMP, and the R-site to the IP₃ transduction pathway, and that these three signal pathways did not have crossing points. Copyright © 2011 Elsevier Inc. All rights reserved.

Theory on the Coupled Stochastic Dynamics of Transcription and Splice-Site Recognition

PubMed Central

Murugan, Rajamanickam; Kreiman, Gabriel

2012-01-01

Eukaryotic genes are typically split into exons that need to be spliced together to form the mature mRNA. The splicing process depends on the dynamics and interactions among transcription by the RNA polymerase II complex (RNAPII) and the spliceosomal complex consisting of multiple small nuclear ribonucleo proteins (snRNPs). Here we propose a biophysically plausible initial theory of splicing that aims to explain the effects of the stochastic dynamics of snRNPs on the splicing patterns of eukaryotic genes. We consider two different ways to model the dynamics of snRNPs: pure three-dimensional diffusion and a combination of three- and one-dimensional diffusion along the emerging pre-mRNA. Our theoretical analysis shows that there exists an optimum position of the splice sites on the growing pre-mRNA at which the time required for snRNPs to find the 5′ donor site is minimized. The minimization of the overall search time is achieved mainly via the increase in non-specific interactions between the snRNPs and the growing pre-mRNA. The theory further predicts that there exists an optimum transcript length that maximizes the probabilities for exons to interact with the snRNPs. We evaluate these theoretical predictions by considering human and mouse exon microarray data as well as RNAseq data from multiple different tissues. We observe that there is a broad optimum position of splice sites on the growing pre-mRNA and an optimum transcript length, which are roughly consistent with the theoretical predictions. The theoretical and experimental analyses suggest that there is a strong interaction between the dynamics of RNAPII and the stochastic nature of snRNP search for 5′ donor splicing sites. PMID:23133354

Characterization and functional analysis of the Paralichthys olivaceus prdm1 gene promoter.

PubMed

Li, Peizhen; Wang, Bo; Cao, Dandan; Liu, Yuezhong; Zhang, Quanqi; Wang, Xubo

2017-10-01

PR domain containing protein 1 (Prdm1) is a transcriptional repressor identified in various species and plays multiple important roles in immune response and embryonic development. However, little is known about the transcriptional regulation of the prdm1 gene. This study aims to characterize the promoter of Paralichthys olivaceus prdm1 (Po-prdm1) gene and determine the regulatory mechanism of Po-prdm1 expression. A 2000bp-long 5'-flanking region (translation initiation site designated as +1) of the Po-prdm1 gene was isolated and characterized. The regulatory elements in this fragment were then investigated and many putative transcription factor (TF) binding sites involved in immunity and multiple tissue development were identified. A 5'-deletion analysis was then conducted, and the ability of the deletion mutants to promote luciferase and green fluorescent protein (GFP) expression in a flounder gill cell line was examined. The results revealed that the minimal promoter is located in the region between -446 and -13bp, and the region between -1415 and -13bp enhanced the promoter activity. Site-directed mutation analysis was subsequently performed on the putative regulatory elements sites, and the results indicated that FOXP1, MSX and BCL6 binding sites play negative functional roles in the regulation of the Po-prdm1 expression in FG cells. In vivo analysis demonstrated that a GFP reporter gene containing 1.4kb-long promoter fragment (-1415/-13) was expressed in the head and trunk muscle fibres of transient transgenic zebrafish embryos. Our study provided the basic information for the exploration of Po-prdm1 regulation and expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiple cis-acting signals, some weak by necessity, collectively direct robust transport of oskar mRNA to the oocyte.

PubMed

Ryu, Young Hee; Kenny, Andrew; Gim, Youme; Snee, Mark; Macdonald, Paul M

2017-09-15

Localization of mRNAs can involve multiple steps, each with its own cis -acting localization signals and transport factors. How is the transition between different steps orchestrated? We show that the initial step in localization of Drosophila oskar mRNA - transport from nurse cells to the oocyte - relies on multiple cis -acting signals. Some of these are binding sites for the translational control factor Bruno, suggesting that Bruno plays an additional role in mRNA transport. Although transport of oskar mRNA is essential and robust, the localization activity of individual transport signals is weak. Notably, increasing the strength of individual transport signals, or adding a strong transport signal, disrupts the later stages of oskar mRNA localization. We propose that the oskar transport signals are weak by necessity; their weakness facilitates transfer of the oskar mRNA from the oocyte transport machinery to the machinery for posterior localization. © 2017. Published by The Company of Biologists Ltd.

Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents.

PubMed

Sutherland, R J; Lehmann, H

2011-06-01

We discuss very recent experiments with rodents addressing the idea that long-term memories initially depending on the hippocampus, over a prolonged period, become independent of it. No unambiguous recent evidence exists to substantiate that this occurs. Most experiments find that recent and remote memories are equally affected by hippocampus damage. Nearly all experiments that report spared remote memories suffer from two problems: retrieval could be based upon substantial regions of spared hippocampus and recent memory is tested at intervals that are of the same order of magnitude as cellular consolidation. Accordingly, we point the way beyond systems consolidation theories, both the Standard Model of Consolidation and the Multiple Trace Theory, and propose a simpler multiple storage site hypothesis. On this view, with event reiterations, different memory representations are independently established in multiple networks. Many detailed memories always depend on the hippocampus; the others may be established and maintained independently. Copyright © 2011 Elsevier Ltd. All rights reserved.

Irreversible adsorption of particles on heterogeneous surfaces.

PubMed

Adamczyk, Zbigniew; Jaszczółt, Katarzyna; Michna, Aneta; Siwek, Barbara; Szyk-Warszyńska, Lilianna; Zembala, Maria

2005-12-30

Methods of theoretical and experimental evaluation of irreversible adsorption of particles, e.g., colloids and globular proteins at heterogeneous surfaces were reviewed. The theoretical models were based on the generalized random sequential adsorption (RSA) approach. Within the scope of these models, localized adsorption of particles occurring as a result of short-ranged attractive interactions with discrete adsorption sites was analyzed. Monte-Carlo type simulations performed according to this model enabled one to determine the initial flux, adsorption kinetics, jamming coverage and the structure of the particle monolayer as a function of the site coverage and the particle/site size ratio, denoted by lambda. It was revealed that the initial flux increased significantly with the site coverage theta(s) and the lambda parameter. This behavior was quantitatively interpreted in terms of the scaled particle theory. It also was demonstrated that particle adsorption kinetics and the jamming coverage increased significantly, at fixed site coverage, when the lambda parameter increased. Practically, for alpha = lambda2theta(s) > 1 the jamming coverage at the heterogeneous surfaces attained the value pertinent to continuous surfaces. The results obtained prove unequivocally that spherically shaped sites were more efficient in binding particles in comparison with disk-shaped sites. It also was predicted that for particle size ratio lambda < 4 the site multiplicity effect plays a dominant role, affecting significantly the structure of particle monolayers and the jamming coverage. Experimental results validating main aspects of these theoretical predictions also have been reviewed. These results were derived by using monodisperse latex particles adsorbing on substrates produced by covering uniform surface by adsorption sites of a desired size, coverage and surface charge. Particle deposition occurred under diffusion-controlled transport conditions and their coverage was evaluated by direct particle counting using the optical and electron microscopy. Adsorption kinetics was quantitatively interpreted in terms of numerical solutions of the governing diffusion equation with the non-linear boundary condition derived from Monte-Carlo simulations. It was proven that for site coverage as low as a few percent the initial flux at heterogeneous surfaces attained the maximum value pertinent to homogeneous surfaces. It also was demonstrated that the structure of larger particle monolayers, characterized in terms of the pair correlation function, showed much more short-range ordering than predicted for homogeneous surface monolayers at the same coverage. The last part of this review was devoted to detection of polyelectrolyte multilayers on various substrates via particle deposition experiments.

Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales

PubMed Central

Wallace, Bryan P.; DiMatteo, Andrew D.; Hurley, Brendan J.; Finkbeiner, Elena M.; Bolten, Alan B.; Chaloupka, Milani Y.; Hutchinson, Brian J.; Abreu-Grobois, F. Alberto; Amorocho, Diego; Bjorndal, Karen A.; Bourjea, Jerome; Bowen, Brian W.; Dueñas, Raquel Briseño; Casale, Paolo; Choudhury, B. C.; Costa, Alice; Dutton, Peter H.; Fallabrino, Alejandro; Girard, Alexandre; Girondot, Marc; Godfrey, Matthew H.; Hamann, Mark; López-Mendilaharsu, Milagros; Marcovaldi, Maria Angela; Mortimer, Jeanne A.; Musick, John A.; Nel, Ronel; Pilcher, Nicolas J.; Seminoff, Jeffrey A.; Troëng, Sebastian; Witherington, Blair; Mast, Roderic B.

2010-01-01

Background Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques — including site-based monitoring, genetic analyses, mark-recapture studies and telemetry — can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine- to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework — including maps and supporting metadata — will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis. PMID:21253007

Multiple criteria approach to site selection of radioactive waste disposal facility in the Republic of Croatia

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

Schaller, A.; Skanata, D.

1995-12-31

Site selection approach to radioactive waste disposal facility, which is under way in Croatia, is presented in the paper. This approach is based on application of certain relevant terrestrial and technical criteria in the site selection process. Basic documentation used for this purpose are regional planning documents prepared by the Regional Planning Institute of Croatia. The basic result of research described in the paper is the proposal of several potential areas which are suitable for siting a radioactive waste repository. All relevant conclusions are based on both data groups -- generic and on-field experienced (measured). Out of a dozen potentialmore » areas, four have been chosen as representative by the authors. The presented comparative analysis was made by means of the VISA II computer code, developed by the V. Belton and SPV Software Products. The code was donated to the APO by the IAEA. The main objective of the paper is to initiate and facilitate further discussions on possible ways of evaluation and comparison of potential areas for sitting of radioactive waste repository in this country, as well as to provide additional contributions to the current site selection process in the Republic of Croatia.« less

Non-peristaltic patterns of motor activity in the guinea-pig proximal colon.

PubMed

Hennig, G W; Gregory, S; Brookes, S J H; Costa, M

2010-06-01

The guinea-pig proximal colon contains semi-solid feces which are propelled by intermittent neural peristaltic waves to the distal colon, where solid pellets are formed. Between propulsive periods, complex motor patterns underlie fluid re-absorption and mixing of contents. Spatio-temporal analysis of video recordings were used to investigate neural and myogenic patterns of non-peristaltic motor activity. At low distension (6 cmH(2)O), two major motor patterns were seen. Narrow rings of constriction (abrupt contractions) occurred at 19 cpm. These previously undescribed contractions occurred, almost simultaneously, at many points along the preparation, with a calculated propagation velocity of 110 mm s(-1). They were abolished by hexamethonium and by tetrodotoxin, indicating they were neurally mediated. Inhibition of nitric oxide synthase resulted in increased frequency of 'abrupt contractions' suggesting ongoing inhibitory modulation by endogenous nitric oxide. After tetrodotoxin, another distinct motor pattern was revealed; 'ripples'(1) consisted of shallow rings of contraction, occurring at 18 cpm and propagating at 2.7-2.9 mm s(-1) orally or aborally from multiple initiation sites. The frequency of 'ripples' increased as intraluminal pressure was raised, becoming very irregular at high distensions. L-type calcium channel blockers and openers affected the amplitude of 'ripples'. No frequency gradient of 'ripples' along the proximal colon was detected. This absence explains the multiple initiation sites which often shifted over time, and the oral and aboral propagation of 'ripples'. The interaction of myogenic 'ripples' with neurogenic 'abrupt contractions' generates localized alternating rings of contractions and dilatation, well suited to effective mixing of contents.

Greenhouse gas balance over thaw-freeze cycles in discontinuous zone permafrost

NASA Astrophysics Data System (ADS)

Wilson, R. M.; Fitzhugh, L.; Whiting, G. J.; Frolking, S.; Harrison, M. D.; Dimova, N.; Burnett, W. C.; Chanton, J. P.

2017-02-01

Peat in the discontinuous permafrost zone contains a globally significant reservoir of carbon that has undergone multiple permafrost-thaw cycles since the end of the mid-Holocene ( 3700 years before present). Periods of thaw increase C decomposition rates which leads to the release of CO2 and CH4 to the atmosphere creating potential climate feedback. To determine the magnitude and direction of such feedback, we measured CO2 and CH4 emissions and modeled C accumulation rates and radiative fluxes from measurements of two radioactive tracers with differing lifetimes to describe the C balance of the peatland over multiple permafrost-thaw cycles since the initiation of permafrost at the site. At thaw features, the balance between increased primary production and higher CH4 emission stimulated by warmer temperatures and wetter conditions favors C sequestration and enhanced peat accumulation. Flux measurements suggest that frozen plateaus may intermittently (order of years to decades) act as CO2 sources depending on temperature and net ecosystem respiration rates, but modeling results suggest that—despite brief periods of net C loss to the atmosphere at the initiation of thaw—integrated over millennia, these sites have acted as net C sinks via peat accumulation. In greenhouse gas terms, the transition from frozen permafrost to thawed wetland is accompanied by increasing CO2 uptake that is partially offset by increasing CH4 emissions. In the short-term (decadal time scale) the net effect of this transition is likely enhanced warming via increased radiative C emissions, while in the long-term (centuries) net C deposition provides a negative feedback to climate warming.

Ectopic Integration of Transforming DNA Is Rare among Neurospora Transformants Selected for Gene Replacement

PubMed Central

Miao, VPW.; Rountree, M. R.; Selker, E. U.

1995-01-01

In a variety of organisms, DNA-mediated transformation experiments commonly produce transformants with multiple copies of the transforming DNA, including both selected and unselected molecules. Such ``cotransformants'' are much more common than expected from the individual transformation frequencies, suggesting that subpopulations of cells, or nuclei, are particularly competent for transformation. We found that Neurospora crassa transformants selected for gene replacement at the am gene had not efficiently incorporated additional DNA, suggesting that nuclei that undergo transformation by homologous recombination are not highly competent at integration of DNA by illegitimate recombination. Spheroplasts were treated with DNA fragments homologous to am and with an Escherichia coli hph plasmid. Transformants were initially selected for hph (hygromycin(R)), allowed to conidiate to generate homokaryons and then selected for either Am(-) (gene replacements) or hph. Surprisingly, most am replacement strains were hygromycin(S) (124/140) and carried no extraneous DNA (116/140). Most transformants selected for hph also had ectopic copies of am DNA and/or multiple copies of hph sequences (32/35), generally at multiple sites, confirming that efficient cotransformation could occur. To test the implication that cotransformation involving gene replacement and ectopic integration is rare, we compared the yields of am replacement strains with or without prior selection for hph. The initial selection did not appreciably help (or hinder) recovery of strains with replacements. PMID:7789758

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks

PubMed Central

Harris, Daniel R.; Baus, Adam D.; Harper, Tamela J.; Jarrett, Traci D.; Pollard, Cecil R.; Talbert, Jeffery C.

2017-01-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites. PMID:28261006

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks.

PubMed

Harris, Daniel R; Baus, Adam D; Harper, Tamela J; Jarrett, Traci D; Pollard, Cecil R; Talbert, Jeffery C

2016-08-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites.

40 CFR 280.63 - Initial site characterization.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Initial site characterization. 280.63... Hazardous Substances § 280.63 Initial site characterization. (a) Unless directed to do otherwise by the implementing agency, owners and operators must assemble information about the site and the nature of the...

Trends and uncertainties in budburst projections of Norway spruce in Northern Europe.

PubMed

Olsson, Cecilia; Olin, Stefan; Lindström, Johan; Jönsson, Anna Maria

2017-12-01

Budburst is regulated by temperature conditions, and a warming climate is associated with earlier budburst. A range of phenology models has been developed to assess climate change effects, and they tend to produce different results. This is mainly caused by different model representations of tree physiology processes, selection of observational data for model parameterization, and selection of climate model data to generate future projections. In this study, we applied (i) Bayesian inference to estimate model parameter values to address uncertainties associated with selection of observational data, (ii) selection of climate model data representative of a larger dataset, and (iii) ensembles modeling over multiple initial conditions, model classes, model parameterizations, and boundary conditions to generate future projections and uncertainty estimates. The ensemble projection indicated that the budburst of Norway spruce in northern Europe will on average take place 10.2 ± 3.7 days earlier in 2051-2080 than in 1971-2000, given climate conditions corresponding to RCP 8.5. Three provenances were assessed separately (one early and two late), and the projections indicated that the relationship among provenance will remain also in a warmer climate. Structurally complex models were more likely to fail predicting budburst for some combinations of site and year than simple models. However, they contributed to the overall picture of current understanding of climate impacts on tree phenology by capturing additional aspects of temperature response, for example, chilling. Model parameterizations based on single sites were more likely to result in model failure than parameterizations based on multiple sites, highlighting that the model parameterization is sensitive to initial conditions and may not perform well under other climate conditions, whether the change is due to a shift in space or over time. By addressing a range of uncertainties, this study showed that ensemble modeling provides a more robust impact assessment than would a single phenology model run.

Quantification of Road Network Vulnerability and Traffic Impacts to Regional Landslide Hazards.

NASA Astrophysics Data System (ADS)

Postance, Benjamin; Hillier, John; Dixon, Neil; Dijkstra, Tom

2015-04-01

Slope instability represents a prevalent hazard to transport networks. In the UK regional road networks are frequently disrupted by multiple slope failures triggered during intense precipitation events; primarily due to a degree of regional homogeneity of slope materials, geomorphology and weather conditions. It is of interest to examine how different locations and combinations of slope failure impact road networks, particularly in the context of projected climate change and a 40% increase in UK road demand by 2040. In this study an extensive number (>50 000) of multiple failure event scenarios are simulated within a dynamic micro simulation to assess traffic impacts during peak flow (7 - 10 AM). Possible failure locations are selected within the county of Gloucestershire (3150 km2) using historic failure sites and British Geological Survey GeoSure data. Initial investigations employ a multiple linear regression analyses to consider the severity of traffic impacts, as measured by time, in respect of spatial and topographical network characteristics including connectivity, density and capacity in proximity to failure sites; the network distance between disruptions in multiple failure scenarios is used to consider the effects of spatial clustering. The UK Department of Transport road travel demand and UKCP09 weather projection data to 2080 provide a suitable basis for traffic simulations and probabilistic slope stability assessments. Future work will thus focus on the development of a catastrophe risk model to simulate traffic impacts under various narratives of future travel demand and slope instability under climatic change. The results of this investigation shall contribute to the understanding of road network vulnerabilities and traffic impacts from climate driven slope hazards.

Geospatial optimization of siting large-scale solar projects

USGS Publications Warehouse

Macknick, Jordan; Quinby, Ted; Caulfield, Emmet; Gerritsen, Margot; Diffendorfer, James E.; Haines, Seth S.

2014-01-01

guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.

Multiple-Use Site Demand Analysis: An Application to the Boundary Waters Canoe Area Wilderness.

ERIC Educational Resources Information Center

Peterson, George L.; And Others

1982-01-01

A single-site, multiple-use model for analyzing trip demand is derived from a multiple site regional model based on utility maximizing choice theory. The model is used to analyze and compare trips to the Boundary Waters Canoe Area Wilderness for several types of use. Travel cost elasticities of demand are compared and discussed. (Authors/JN)

Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid

PubMed Central

Kwon, Inchan; Choi, Eun Sil

2016-01-01

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation. PMID:27028506

Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid.

PubMed

Kwon, Inchan; Choi, Eun Sil

2016-01-01

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation.

Cooperative mission execution and planning

NASA Astrophysics Data System (ADS)

Flann, Nicholas S.; Saunders, Kevin S.; Pells, Larry

1998-08-01

Utilizing multiple cooperating autonomous vehicles to perform tasks enhances robustness and efficiency over the use of a single vehicle. Furthermore, because autonomous vehicles can be controlled precisely and their status known accurately in real time, new types of cooperative behaviors are possible. This paper presents a working system called MEPS that plans and executes missions for multiple autonomous vehicles in large structured environments. Two generic spatial tasks are supported, to sweep an area and to visit a location while activating on-board equipment. Tasks can be entered both initially by the user and dynamically during mission execution by both users and vehicles. Sensor data and task achievement data is shared among the vehicles enabling them to cooperatively adapt to changing environmental, vehicle and tasks conditions. The system has been successfully applied to control ATV and micro-robotic vehicles in precision agriculture and waste-site characterization environments.

Two ribosome recruitment sites direct multiple translation events within HIV1 Gag open reading frame.

PubMed

Deforges, Jules; de Breyne, Sylvain; Ameur, Melissa; Ulryck, Nathalie; Chamond, Nathalie; Saaidi, Afaf; Ponty, Yann; Ohlmann, Theophile; Sargueil, Bruno

2017-07-07

In the late phase of the HIV virus cycle, the unspliced genomic RNA is exported to the cytoplasm for the necessary translation of the Gag and Gag-pol polyproteins. Three distinct translation initiation mechanisms ensuring Gag production have been described with little rationale for their multiplicity. The Gag-IRES has the singularity to be located within Gag ORF and to directly interact with ribosomal 40S. Aiming at elucidating the specificity and the relevance of this interaction, we probed HIV-1 Gag-IRES structure and developed an innovative integrative modelling strategy to take into account all the gathered information. We propose a novel Gag-IRES secondary structure strongly supported by all experimental data. We further demonstrate the presence of two regions within Gag-IRES that independently and directly interact with the ribosome. Importantly, these binding sites are functionally relevant to Gag translation both in vitro and ex vivo. This work provides insight into the Gag-IRES molecular mechanism and gives compelling evidence for its physiological importance. It allows us to propose original hypotheses about the IRES physiological role and conservation among primate lentiviruses. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Multiple effects of S13 in modulating the strength of intersubunit interactions in the ribosome during translation.

PubMed

Cukras, Anthony R; Green, Rachel

2005-05-27

The ribosomal protein S13 is found in the head region of the small subunit, where it interacts with the central protuberance of the large ribosomal subunit and with the P site-bound tRNA through its extended C terminus. The bridging interactions between the large and small subunits are dynamic, and are thought to be critical in orchestrating the molecular motions of the translation cycle. S13 provides a direct link between the tRNA-binding site and the movements in the head of the small subunit seen during translocation, thereby providing a possible pathway of signal transduction. We have created and characterized an rpsM(S13)-deficient strain of Escherichia coli and have found significant defects in subunit association, initiation and translocation through in vitro assays of S13-deficient ribosomes. Targeted mutagenesis of specific bridge and tRNA contact elements in S13 provides evidence that these two interaction domains play critical roles in maintaining the fidelity of translation. This ribosomal protein thus appears to play a non-essential, yet important role by modulating subunit interactions in multiple steps of the translation cycle.

Low-cost embedded systems for democratizing ocean sensor technology in the coastal zone

NASA Astrophysics Data System (ADS)

Glazer, B. T.; Lio, H. I.

2017-12-01

Environmental sciences suffer from undersampling. Enabling sustained and unattended data collection in the coastal zone typically involves expensive instrumentation and infrastructure deployed as cabled observatories or moorings with little flexibility in deployment location following initial installation. High costs of commercially-available or custom instruments have limited the number of sensor sites that can be targeted by academic researchers, and have also limited engagement with the public. We have developed a novel, low-cost, open-source sensor and software platform to enable wireless data transfer of biogeochemical sensors in the coastal zone. The platform is centered upon widely available, low-cost, single board computers and microcontrollers. We have used a blend of on-hand research-grade sensors and low-cost open-source electronics that can be assembled by tech-savvy non-engineers. Robust, open-source code that remains customizable for specific miniNode configurations can match a specific site's measurement needs, depending on the scientific research priorities. We have demonstrated prototype capabilities and versatility through lab testing and field deployments of multiple sensor nodes with multiple sensor inputs, all of which are streaming near-real-time data from Kaneohe Bay over wireless RF links to a shore-based base station.

Reversible multi-electron redox chemistry of π-conjugated N-containing heteroaromatic molecule-based organic cathodes

NASA Astrophysics Data System (ADS)

Peng, Chengxin; Ning, Guo-Hong; Su, Jie; Zhong, Guiming; Tang, Wei; Tian, Bingbing; Su, Chenliang; Yu, Dingyi; Zu, Lianhai; Yang, Jinhu; Ng, Man-Fai; Hu, Yong-Sheng; Yang, Yong; Armand, Michel; Loh, Kian Ping

2017-07-01

Even though organic molecules with well-designed functional groups can be programmed to have high electron density per unit mass, their poor electrical conductivity and low cycle stability limit their applications in batteries. Here we report a facile synthesis of π-conjugated quinoxaline-based heteroaromatic molecules (3Q) by condensation of cyclic carbonyl molecules with o-phenylenediamine. 3Q features a number of electron-deficient pyrazine sites, where multiple redox reactions take place. When hybridized with graphene and coupled with an ether-based electrolyte, an organic cathode based on 3Q molecules displays a discharge capacity of 395 mAh g-1 at 400 mA g-1 (1C) in the voltage range of 1.2-3.9 V and a nearly 70% capacity retention after 10,000 cycles at 8 A g-1. It also exhibits a capacity of 222 mAh g-1 at 20C, which corresponds to 60% of the initial specific capacity. Our results offer evidence that heteroaromatic molecules with multiple redox sites are promising in developing high-energy-density, long-cycle-life organic rechargeable batteries.

Laying the foundation for Connect to Protect: a multi-site community mobilization intervention to reduce HIV/AIDS incidence and prevalence among urban youth.

PubMed

Ziff, Mauri A; Harper, Gary W; Chutuape, Kate S; Deeds, Bethany Griffin; Futterman, Donna; Francisco, Vincent T; Muenz, Larry R; Ellen, Jonathan M

2006-05-01

Despite the considerable resources that have been dedicated to HIV prevention interventions and services over the past decade, HIV incidence among young people in the United States remains alarmingly high. One reason is that the majority of prevention efforts continue to focus solely on modifying individual behavior, even though public health research strongly suggests that changes to a community's structural elements, such as their programs, practices, and laws or policies, may result in more effective and sustainable outcomes. Connect to Protect is a multi-city community mobilization intervention that focuses on altering or creating community structural elements in ways that will ultimately reduce youth HIV incidence and prevalence. The project, which spans 6 years, is sponsored by the Adolescent Medicine Trials Network for HIV/AIDS Interventions at multiple urban clinical research sites. This paper provides an overview of the study's three phases and describes key factors in setting a firm foundation for the initiation and execution of this type of undertaking. Connect to Protect's community mobilization approach to achieving structural change represents a relatively new and broad direction in HIV prevention research. To optimize opportunities for its success, time and resources must be initially placed into laying the groundwork. This includes activities such as building a strong overarching study infrastructure to ensure protocol tasks can be met across sites; tapping into local site and community expertise and knowledge; forming collaborative relationships between sites and community organizations and members; and fostering community input on and support for changes at a structural level. Failing to take steps such as these may lead to insurmountable implementation problems for an intervention of this kind.

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

Griffith, K.D.; Read, E.J.; Carrasquillo, J.A.

Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skinmore » were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL.« less

Challenges faced in implementation of a telehealth enabled chronic wound care system.

PubMed

Barrett, M; Larson, A; Carville, K; Ellis, I

2009-01-01

In the rural Midwest region of Western Australia (WA), wound care is a major burden on the healthcare system. Optimal wound care was found to be impeded by issues that included the involvement of multiple healthcare providers, incomplete and inconsistent documentation, and limited access to expert review. A telehealth solution was trailed in 2007. To describe the systemic barriers encountered in implementing a telehealth program in rural WA and to provide recommendations for future telehealth initiatives. This study trialled the use of a shared electronic wound imaging and reporting system in combination with an expert remote wound consultation service for the management of patients with chronic wounds in the Midwest of WA. The trial sites included rural hospital out-patient clinics, a private domiciliary nursing service, residential aged care facilities, general practices and a podiatry clinic. The implementation conformed to accepted best practice in introducing telehealth initiatives. During the trial 12 sites had the relevant software installed and were able to access a central server. Although a total of 41 patients with chronic wounds were enrolled, four sites did not enroll any patients and only two sites successfully incorporated the system into regular practice. Major obstacles were workforce issues and significant delays in installing the software at some sites. Only 47% of the healthcare providers trained to use the software at the beginning of the trial were still employed when the trial ended. Prolonged periods of vacant positions at one remote clinic and an aged care facility made it impossible for the remaining providers to allocate time for using the wound care software. The disease burden of the patient group, funding models and workforce shortages frustrated the successful adoption of an evidence based strategy that was known to improve health outcomes.

Models of initial training and pathways to registration: a selective review of policy in professional regulation.

PubMed

Fealy, Gerard M; Carney, Marie; Drennan, Jonathan; Treacy, Margaret; Burke, Jacqueline; O'Connell, Dympna; Howley, Breeda; Clancy, Alison; McHugh, Aine; Patton, Declan; Sheerin, Fintan

2009-09-01

To provide a synthesis of literature on international policy concerning professional regulation in nursing and midwifery, with reference to routes of entry into training and pathways to licensure. Internationally, there is evidence of multiple points of entry into initial training, multiple divisions of the professional register and multiple pathways to licensure. Policy documents and commentary articles concerned with models of initial training and pathways to licensure were reviewed. Item selection, quality appraisal and data extraction were undertaken and documentary analysis was performed on all retrieved texts. Case studies of five Western countries indicate no single uniform system of routes of entry into initial training and no overall consensus regarding the optimal model of initial training. Multiple regulatory systems, with multiple routes of entry into initial training and multiple pathways to licensure pose challenges, in terms of achieving commonly-agreed understandings of practice competence. The variety of models of initial training present nursing managers with challenges in the recruitment and deployment of personnel trained in many different jurisdictions. Nursing managers need to consider the potential for considerable variation in competency repertoires among nurses trained in generic and specialist initial training models.

Nucleosome occupancy as a novel chromatin parameter for replication origin functions

PubMed Central

Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio

2017-01-01

Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

DOE PAGES

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela; ...

2017-03-15

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Extensive interactions between HIV TAT and TAF(II)250.

PubMed

Weissman, J D; Hwang, J R; Singer, D S

2001-03-09

The HIV transactivator, Tat, has been shown to be capable of potent repression of transcription initiation. Repression is mediated by the C-terminal segment of Tat, which binds the TFIID component, TAF(II)250, although the site(s) of interaction were not defined previously. We now report that the interaction between Tat and TAF(II)250 is extensive and involves multiple contacts between the Tat protein and TAF(II)250. The C-terminal domain of Tat, which is necessary for repression of transcription initiation, binds to a segment of TAF(II)250 that encompasses its acetyl transferase (AT) domain (885-1034 amino acids (aa)). Surprisingly, the N-terminal segment of Tat, which contains its activation domains, also binds to TAF(II)250 and interacts with two discontinuous segments of TAF(II)250 located between 885 and 984 aa and 1120 and 1279 aa. Binding of Tat to the 885-984 aa segment of TAF(II)250 requires the cysteine-rich domain of Tat, but not the acidic or glutamine-rich domains. Binding by the N-terminal domain of Tat to the 1120-1279 aa TAF(II)250 segment does not involve the acidic, cysteine- or glutamine-rich domains. Repression of transcription initiation by Tat requires functional TAF(II)250. We now demonstrate that transcription of the HIV LTR does not depend on TAF(II)250 which may account for its resistance to Tat mediated repression.

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

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

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Dislodgement of variceal bands after esophageal balloon tamponade for variceal bleeding.

PubMed

Mogrovejo, Estela; Manickam, Palaniappan; Polidori, Gregg; Cappell, Mitchell S

2014-01-01

A 43-year-old male with alcoholic cirrhosis underwent EGD for hematemesis which revealed bleeding, grade II, lower esophageal varices that were endoscopically ligated with 6 bands. All the bands remained attached to varices at the completion of EGD. Despite apparent initial hemostasis, balloon tamponade was performed one hour later for suspected continued bleeding. Due to suspected continuing bleeding, EGD was repeated 4 h after initial EGD, and 3 h after balloon tamponade. This EGD revealed the esophageal varices; none of the bands remaining on esophageal mucosa; multiple mucosal stigmata likely from trauma at initial site of variceal bands before dislodgement; and 3 dislodged bands in gastric body, duodenal bulb, or descending duodenum. The patient expired 17 h thereafter from hypovolemic shock. This single report may suggest an apparently novel, balloon tamponade complication: dislodgement of previously placed, endoscopic bands. The proposed pathophysiology is release of bands by stretching entrapped, esophageal mucosa during esophageal balloon tamponade. This complication, if confirmed, might render balloon tamponade a less desirable option very soon after band ligation.

Nursing Home Medication Reconciliation: A Quality Improvement Initiative.

PubMed

Tong, Monica; Oh, Hye Young; Thomas, Jennifer; Patel, Sheila; Hardesty, Jennifer L; Brandt, Nicole J

2017-04-01

The current quality improvement initiative evaluated the medication reconciliation process within select nursing homes in Washington, DC. The identification of common types of medication discrepancies through monthly retrospective chart reviews of newly admitted patients in two different nursing homes were described. The use of high-risk medications, namely antidiabetic, anticoagulant, and opioid agents, was also recorded. A standardized spreadsheet tool based on multiple medication reconciliation implementation tool kits was created to record the information. The five most common medication discrepancies were incorrect indication (21%), no monitoring parameters (17%), medication name omitted (11%), incorrect dose (10%), and incorrect frequency (8%). Antidiabetic agents in both sites were the most used high-risk medication. This initiative highlights that medication discrepancies on admission are common in nursing homes and may be clinically impactful. More attention needs to be given to work flow processes to improve medication reconciliation considering the increased risk for adverse drug events and hospitalizations. [Journal of Gerontological Nursing and Mental Health Services, 43(4), 9-14.]. Copyright 2017, SLACK Incorporated.

Practical use of bone scan in patients with an osteoporotic vertebral compression fracture.

PubMed

Jun, Deuk Soo; An, Byoung Keun; Yu, Chang Hun; Hwang, Kyung Hoon; Paik, Je Won

2015-02-01

Rib fractures are one of main causes of chest or flank pain when related to an osteoporotic vertebral compression fracture (OVCF). The authors investigated the incidence and risk factors of rib fracture in 284 patients with OVCF using bone scans and evaluated the feasibility as to whether bone scans could be utilized as a useful screening tool. Hot uptake lesions on ribs were found in 122 cases (43.0%). The factors analyzed were age, sex, number and locations of fractured vertebrae, BMD, and compression rates as determined using initial radiography. However, no statistical significances were found. In 16 cases (5.6%), there were concurrent multiple fractures of both the thoracic and lumbar spines not detected by single site MRI. Sixty cases (21.1%) of OVCF with the a compression rate of less than 15% could not be identified definitely by initial plain radiography, but were confirmed by bone scans. It is concluded that a bone scan has outstanding ability for the screening of rib fractures associated with OVCF. Non-adjacent multiple fractures in both thoracic and lumbar spines and fractures not identified definitely by plain radiography were detected on bone scans, which provided a means for determining management strategies and predicting prognosis.

The SCALE-UP Project

NASA Astrophysics Data System (ADS)

Beichner, Robert

2015-03-01

The Student Centered Active Learning Environment with Upside-down Pedagogies (SCALE-UP) project was developed nearly 20 years ago as an economical way to provide collaborative, interactive instruction even for large enrollment classes. Nearly all research-based pedagogies have been designed with fairly high faculty-student ratios. The economics of introductory courses at large universities often precludes that situation, so SCALE-UP was created as a way to facilitate highly collaborative active learning with large numbers of students served by only a few faculty and assistants. It enables those students to learn and succeed not only in acquiring content, but also to practice important 21st century skills like problem solving, communication, and teamsmanship. The approach was initially targeted at undergraduate science and engineering students taking introductory physics courses in large enrollment sections. It has since expanded to multiple content areas, including chemistry, math, engineering, biology, business, nursing, and even the humanities. Class sizes range from 24 to over 600. Data collected from multiple sites around the world indicates highly successful implementation at more than 250 institutions. NSF support was critical for initial development and dissemination efforts. Generously supported by NSF (9752313, 9981107) and FIPSE (P116B971905, P116B000659).

Diphenylpyrazoles as Replication Protein A inhibitors

DOE PAGES

Waterson, Alex G.; Kennedy, J. Phillip; Patrone, James D.; ...

2014-11-11

Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here we describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA–protein interactions. Lastly, we evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein–protein interactions.

A field study of air flow and turbulent features of advection fog

NASA Technical Reports Server (NTRS)

Connell, J. D.

1979-01-01

The setup and initial operation of a set of specialized meteorological data collection hardware are described. To study the life cycle of advection fogs at a lake test site, turbulence levels in the fog are identified, and correlated with the temperature gradients and mean wind profiles. A meteorological tower was instrumented to allow multiple-level measurements of wind and temperature on a continuous basis. Additional instrumentation was: (1)hydrothermograph, (2)microbarograph, (3)transmissometers, and (4)a boundary layer profiler. Two types of fogs were identified, and important differences in the turbulence scales were noted.

Parallel Low-Loss Measurement of Multiple Atomic Qubits

NASA Astrophysics Data System (ADS)

Kwon, Minho; Ebert, Matthew F.; Walker, Thad G.; Saffman, M.

2017-11-01

We demonstrate low-loss measurement of the hyperfine ground state of rubidium atoms by state dependent fluorescence detection in a dipole trap array of five sites. The presence of atoms and their internal states are minimally altered by utilizing circularly polarized probe light and a strictly controlled quantization axis. We achieve mean state detection fidelity of 97% without correcting for imperfect state preparation or background losses, and 98.7% when corrected. After state detection and correction for background losses, the probability of atom loss due to the state measurement is <2 % and the initial hyperfine state is preserved with >98 % probability.

Identification of HIV infection-related DNA methylation sites and advanced epigenetic aging in HIV-positive, treatment-naive U.S. veterans.

PubMed

Nelson, Kristin N; Hui, Qin; Rimland, David; Xu, Ke; Freiberg, Matthew S; Justice, Amy C; Marconi, Vincent C; Sun, Yan V

2017-02-20

HIV-positive individuals are at higher risk than healthy persons for aging-related diseases, including myocardial infarction and non-AIDS defining cancers. Recent evidence suggests that HIV infection may modulate changes in the host cell epigenome, and these changes represent a potential mechanism through which HIV infection accelerates aging. We assessed the difference in DNA methylation (DNAm) age, an aging marker involving multiple age-related cytosine-guanine dinucleotide (CpG) sites, among antiretroviral treatment (ART)-naive HIV-positive and HIV-negative individuals in a cohort of veterans from the Veterans Aging Cohort Study. Peripheral blood samples were collected from 19 ART-naive, HIV-positive, and 19 HIV-negative male participants, matched by age and race. Blood samples were collected from HIV-positive participants 7-11 years after ART initiation. We compared DNAm age between HIV-positive and HIV-negative groups at baseline and between HIV-positive patients at baseline and follow-up. We also performed an epigenome-wide analysis to identify CpG methylation sites associated with HIV infection. DNAm age in HIV-positive individuals is, on average, 11.2 years higher than HIV study participants at baseline, and two of 10 HIV-positive individuals showed an increase in DNAm age after ART initiation. Epigenome-wide association studies showed an association of HIV infection with one site, in gene VPS37B, which approached statistical significance in our cohort (P = 3.30 × 10, Bonferroni-corrected threshold = 1.22 × 10) and was replicated in a second, larger cohort. ART treatment-naive HIV-positive individuals have significantly older DNAm age compared to HIV-negative individuals in the Veterans Aging Cohort Study cohort. Longitudinal changes in DNAm age are highly variable across individuals after initiation of antiretroviral therapy.

Use of Data Libraries for IAEA Nuclear Security Assessment Methodologies (NUSAM) [section 5.4

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

Shull, D.; Lane, M.

2015-06-23

Data libraries are essential for the characterization of the facility and provide the documented input which enables the facility assessment results and subsequent conclusions. Data Libraries are historical, verifiable, quantified, and applicable collections of testing data on different types of barriers, sensors, cameras, procedures, and/or personnel. Data libraries are developed and maintained as part of any assessment program or process. Data is collected during the initial stages of facility characterization to aid in the model and/or simulation development process. Data library values may also be developed through the use of state testing centers and/or site resources by testing different typesmore » of barriers, sensors, cameras, procedures, and/or personnel. If no data exists, subject matter expert opinion and manufacturer's specifications/ testing values can be the basis for initially assigning values, but are generally less reliable and lack appropriate confidence measures. The use of existing data libraries that have been developed by a state testing organization reduces the assessment costs by establishing standard delay, detection and assessment values for use by multiple sites or facilities where common barriers and alarms systems exist.« less

Optimal design of compact and connected nature reserves for multiple species.

PubMed

Wang, Yicheng; Önal, Hayri

2016-04-01

When designing a conservation reserve system for multiple species, spatial attributes of the reserves must be taken into account at species level. The existing optimal reserve design literature considers either one spatial attribute or when multiple attributes are considered the analysis is restricted only to one species. We built a linear integer programing model that incorporates compactness and connectivity of the landscape reserved for multiple species. The model identifies multiple reserves that each serve a subset of target species with a specified coverage probability threshold to ensure the species' long-term survival in the reserve, and each target species is covered (protected) with another probability threshold at the reserve system level. We modeled compactness by minimizing the total distance between selected sites and central sites, and we modeled connectivity of a selected site to its designated central site by selecting at least one of its adjacent sites that has a nearer distance to the central site. We considered structural distance and functional distances that incorporated site quality between sites. We tested the model using randomly generated data on 2 species, one ground species that required structural connectivity and the other an avian species that required functional connectivity. We applied the model to 10 bird species listed as endangered by the state of Illinois (U.S.A.). Spatial coherence and selection cost of the reserves differed substantially depending on the weights assigned to these 2 criteria. The model can be used to design a reserve system for multiple species, especially species whose habitats are far apart in which case multiple disjunct but compact and connected reserves are advantageous. The model can be modified to increase or decrease the distance between reserves to reduce or promote population connectivity. © 2015 Society for Conservation Biology.

40 CFR Table 5 to Subpart Llll of... - Summary of Reporting Requirements for New Sewage Sludge Incineration Units a

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Documentation for siting requirements. 4. Anticipated date of initial startup. § 60.4915(a). Notification of initial startup Prior to initial startup 1. Maximum design dry sewage sludge burning capacity2.... 4. Anticipated date of initial startup. 5. Site-specific monitoring plan. 6. The site-specific...

40 CFR Table 5 to Subpart Llll of... - Summary of Reporting Requirements for New Sewage Sludge Incineration Units a

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Documentation for siting requirements. 4. Anticipated date of initial startup. § 60.4915(a). Notification of initial startup Prior to initial startup 1. Maximum design dry sewage sludge burning capacity2.... 4. Anticipated date of initial startup. 5. Site-specific monitoring plan. 6. The site-specific...

Structural dissection of an interaction between transcription initiation and termination factors implicated in promoter-terminator cross-talk.

PubMed

Bratkowski, Matthew; Unarta, Ilona Christy; Zhu, Lizhe; Shubbar, Murtada; Huang, Xuhui; Liu, Xin

2018-02-02

Functional cross-talk between the promoter and terminator of a gene has long been noted. Promoters and terminators are juxtaposed to form gene loops in several organisms, and gene looping is thought to be involved in transcriptional regulation. The general transcription factor IIB (TFIIB) and the C-terminal domain phosphatase Ssu72, essential factors of the transcription preinitiation complex and the mRNA processing and polyadenylation complex, respectively, are important for gene loop formation. TFIIB and Ssu72 interact both genetically and physically, but the molecular basis of this interaction is not known. Here we present a crystal structure of the core domain of TFIIB in two new conformations that differ in the relative distance and orientation of the two cyclin-like domains. The observed extraordinary conformational plasticity may underlie the binding of TFIIB to multiple transcription factors and promoter DNAs that occurs in distinct stages of transcription, including initiation, reinitiation, and gene looping. We mapped the binding interface of the TFIIB-Ssu72 complex using a series of systematic, structure-guided in vitro binding and site-specific photocross-linking assays. Our results indicate that Ssu72 competes with acidic activators for TFIIB binding and that Ssu72 disrupts an intramolecular TFIIB complex known to impede transcription initiation. We also show that the TFIIB-binding site on Ssu72 overlaps with the binding site of symplekin, a component of the mRNA processing and polyadenylation complex. We propose a hand-off model in which Ssu72 mediates a conformational transition in TFIIB, accounting for the role of Ssu72 in transcription reinitiation, gene looping, and promoter-terminator cross-talk. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

The synergy of the whole: building a global system for clinical trials to accelerate medicines development.

PubMed

Koski, Greg; Tobin, Mary F; Whalen, Matthew

2014-10-01

The pharmaceutical industry, once highly respected, productive, and profitable, is in the throes of major change driven by many forces, including economics, science, regulation, and ethics. A variety of initiatives and partnerships have been launched to improve efficiency and productivity but without significant effect because they have failed to consider the process as a system. Addressing the challenges facing this complex endeavor requires more than modifications of individual processes; it requires a fully integrated application of systems thinking and an understanding of the desired goals and complex interactions among essential components and stakeholders of the whole. A multistakeholder collaborative effort, led by the Alliance for Clinical Research Excellence and Safety (ACRES), a global nonprofit organization operating in the public interest, is now under way to build a shared global system for clinical research. Its systems approach focuses on the interconnection of stakeholders at critical points of interaction within 4 operational domains: site development and support, quality management, information technology, and safety. The ACRES initiatives, Site Accreditation and Standards, Product Safety Culture, Global Ethical Review and Regulatory Innovation, and Quality Assurance and Safety, focus on building and implementing systems solutions. Underpinning these initiatives is an open, shared, integrated technology (site and optics and quality informatics initiative). We describe the rationale, challenges, progress, and successes of this effort to date and lessons learned. The complexity and fragmentation of the intensely proprietary ecosystem of drug development, challenging regulatory climate, and magnitude of the endeavor itself pose significant challenges, but the economic, social, and scientific rewards will more than justify the effort. An effective alliance model requires a willingness of multiple stakeholders to work together to build a shared system within a noncompetitive space that will have major benefits for all, including better access to medicines, better health, and more productive lives. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Videoconferencing for site initiations in clinical studies: Mixed methods evaluation of usability, acceptability, and impact on recruitment.

PubMed

Randell, Rebecca; Backhouse, Michael R; Nelson, E Andrea

2016-12-01

A critical issue for multicentre clinical studies is conducting site initiations, ensuring sites are trained in study procedures and comply with relevant governance requirements before they begin recruiting patients. How technology can support site initiations has not previously been explored. This study sought to evaluate use of off-the-shelf web-based videoconferencing to deliver site initiations for a large national multicentre study. Participants in the initiations, including podiatrists, diabetologists, trial coordinators, and research nurses, completed an online questionnaire based on the System Usability Scale (SUS) (N = 15). This was followed by semi-structured interviews, with a consultant diabetologist, a trial coordinator, and three research nurses, exploring perceived benefits and limitations of videoconferencing. The mean SUS score for the videoconferencing platform was 87.2 (SD = 13.7), suggesting a good level of usability. Interview participants perceived initiations delivered by videoconferencing as being more interactive and easier to follow than those delivered by teleconference. In comparison to face-to-face initiations, videoconferencing takes less time, easily fitting in with the work of staff at the local sites. Perceptions of impact on communication varied according to the hardware used. Off-the-shelf videoconferencing is a viable alternative to face-to-face site initiations and confers advantages over teleconferencing.

Microdomains of muscarinic acetylcholine and Ins(1,4,5)P3 receptors create ‘Ins(1,4,5)P3 junctions’ and sites of Ca2+ wave initiation in smooth muscle

PubMed Central

Olson, Marnie L.; Sandison, Mairi E.; Chalmers, Susan; McCarron, John G.

2012-01-01

Summary Increases in cytosolic Ca2+ concentration ([Ca2+]c) mediated by inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3, hereafter InsP3] regulate activities that include division, contraction and cell death. InsP3-evoked Ca2+ release often begins at a single site, then regeneratively propagates through the cell as a Ca2+ wave. The Ca2+ wave consistently begins at the same site on successive activations. Here, we address the mechanisms that determine the Ca2+ wave initiation site in intestinal smooth muscle cells. Neither an increased sensitivity of InsP3 receptors (InsP3R) to InsP3 nor regional clustering of muscarinic receptors (mAChR3) or InsP3R1 explained the selection of an initiation site. However, examination of the overlap of mAChR3 and InsP3R1 localisation, by centre of mass analysis, revealed that there was a small percentage (∼10%) of sites that showed colocalisation. Indeed, the extent of colocalisation was greatest at the Ca2+ wave initiation site. The initiation site might arise from a selective delivery of InsP3 from mAChR3 activity to particular InsP3Rs to generate faster local [Ca2+]c increases at sites of colocalisation. In support of this hypothesis, a localised subthreshold ‘priming’ InsP3 concentration applied rapidly, but at regions distant from the initiation site, shifted the wave to the site of the priming. Conversely, when the Ca2+ rise at the initiation site was rapidly and selectively attenuated, the Ca2+ wave again shifted and initiated at a new site. These results indicate that Ca2+ waves initiate where there is a structural and functional coupling of mAChR3 and InsP3R1, which generates junctions in which InsP3 acts as a highly localised signal by being rapidly and selectively delivered to InsP3R1. PMID:22946060

Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes

PubMed Central

Hinnebusch, Alan G.

2011-01-01

Summary: The correct translation of mRNA depends critically on the ability to initiate at the right AUG codon. For most mRNAs in eukaryotic cells, this is accomplished by the scanning mechanism, wherein the small (40S) ribosomal subunit attaches to the 5′ end of the mRNA and then inspects the leader base by base for an AUG in a suitable context, using complementarity with the anticodon of methionyl initiator tRNA (Met-tRNAiMet) as the key means of identifying AUG. Over the past decade, a combination of yeast genetics, biochemical analysis in reconstituted systems, and structural biology has enabled great progress in deciphering the mechanism of ribosomal scanning. A robust molecular model now exists, describing the roles of initiation factors, notably eukaryotic initiation factor 1 (eIF1) and eIF1A, in stabilizing an “open” conformation of the 40S subunit with Met-tRNAiMet bound in a low-affinity state conducive to scanning and in triggering rearrangement into a “closed” conformation incompatible with scanning, which features Met-tRNAiMet more tightly bound to the “P” site and base paired with AUG. It has also emerged that multiple DEAD-box RNA helicases participate in producing a single-stranded “landing pad” for the 40S subunit and in removing the secondary structure to enable the mRNA to traverse the 40S mRNA-binding channel in the single-stranded form for base-by-base inspection in the P site. PMID:21885680

Variation in Treatment of Displaced Geriatric Acetabular Fractures Among 15 Level-I Trauma Centers.

PubMed

Manson, Theodore T; Reider, Lisa; OʼToole, Robert V; Scharfstein, Daniel O; Tornetta, Paul; Gary, Joshua L

2016-09-01

To document the initial treatment of displaced acetabular fractures among older adults across multiple trauma centers and to investigate the factors that influence the decision to operate and the choice of operative procedure [open reduction internal fixation (ORIF) vs. total hip arthroplasty (THA)]. Retrospective observational study. Fifteen US level-I trauma centers participating in the Major Extremity Trauma Research Consortium. Overall, 269 patients aged 60 years or older admitted for the treatment of a displaced acetabular fracture. None. Treatment. Sixty percent of fractures (n = 162) were treated operatively. Younger age (<80 years), injury from high-energy mechanism, fractures with femoral head impaction, and fractures without hip congruency were significantly associated with receiving operative treatment (P < 0.05). Significant site variation in operative versus nonoperative treatment occurred even after accounting for these factors (P = 0.0044). Among operatively treated patients, 88% (n = 142) received ORIF and 12% (n = 20) received THA as the initial treatment. Women were more likely to be treated with initial THA compared with men; of the known risk factors for poor outcomes with ORIF (ie, dome or roof impaction, femoral head impaction, or posterior wall involvement), only dome impaction was significantly associated with receiving initial THA (P < 0.05). Currently, no treatment guidelines exist for acetabular fractures in older adults, which likely explains the significant site variation in operative versus nonoperative treatment. This study identifies patient and injury factors that drive treatment decisions, which will be important in planning and designing future trials needed to determine the best treatment for these fractures.

Diffusional correlations among multiple active sites in a single enzyme.

PubMed

Echeverria, Carlos; Kapral, Raymond

2014-04-07

Simulations of the enzymatic dynamics of a model enzyme containing multiple substrate binding sites indicate the existence of diffusional correlations in the chemical reactivity of the active sites. A coarse-grain, particle-based, mesoscopic description of the system, comprising the enzyme, the substrate, the product and solvent, is constructed to study these effects. The reactive and non-reactive dynamics is followed using a hybrid scheme that combines molecular dynamics for the enzyme, substrate and product molecules with multiparticle collision dynamics for the solvent. It is found that the reactivity of an individual active site in the multiple-active-site enzyme is reduced substantially, and this effect is analyzed and attributed to diffusive competition for the substrate among the different active sites in the enzyme.

Porting Social Media Contributions with SIOC

NASA Astrophysics Data System (ADS)

Bojars, Uldis; Breslin, John G.; Decker, Stefan

Social media sites, including social networking sites, have captured the attention of millions of users as well as billions of dollars in investment and acquisition. To better enable a user's access to multiple sites, portability between social media sites is required in terms of both (1) the personal profiles and friend networks and (2) a user's content objects expressed on each site. This requires representation mechanisms to interconnect both people and objects on the Web in an interoperable, extensible way. The Semantic Web provides the required representation mechanisms for portability between social media sites: it links people and objects to record and represent the heterogeneous ties that bind each to the other. The FOAF (Friend-of-a-Friend) initiative provides a solution to the first requirement, and this paper discusses how the SIOC (Semantically-Interlinked Online Communities) project can address the latter. By using agreed-upon Semantic Web formats like FOAF and SIOC to describe people, content objects, and the connections that bind them together, social media sites can interoperate and provide portable data by appealing to some common semantics. In this paper, we will discuss the application of Semantic Web technology to enhance current social media sites with semantics and to address issues with portability between social media sites. It has been shown that social media sites can serve as rich data sources for SIOC-based applications such as the SIOC Browser, but in the other direction, we will now show how SIOC data can be used to represent and port the diverse social media contributions (SMCs) made by users on heterogeneous sites.

NACP Synthesis: Evaluating modeled carbon state and flux variables against multiple observational constraints (Invited)

NASA Astrophysics Data System (ADS)

Thornton, P. E.; Nacp Site Synthesis Participants

2010-12-01

The North American Carbon Program (NACP) synthesis effort includes an extensive intercomparison of modeled and observed ecosystem states and fluxes preformed with multiple models across multiple sites. The participating models span a range of complexity and intended application, while the participating sites cover a broad range of natural and managed ecosystems in North America, from the subtropics to arctic tundra, and coastal to interior climates. A unique characteristic of this collaborative effort is that multiple independent observations are available at all sites: fluxes are measured with the eddy covariance technique, and standard biometric and field sampling methods provide estimates of standing stock and annual production in multiple categories. In addition, multiple modeling approaches are employed to make predictions at each site, varying, for example, in the use of diagnostic vs. prognostic leaf area index. Given multiple independent observational constraints and multiple classes of model, we evaluate the internal consistency of observations at each site, and use this information to extend previously derived estimates of uncertainty in the flux observations. Model results are then compared with all available observations and models are ranked according to their consistency with each type of observation (high frequency flux measurement, carbon stock, annual production). We demonstrate a range of internal consistency across the sites, and show that some models which perform well against one observational metric perform poorly against others. We use this analysis to construct a hypothesis for combining eddy covariance, biometrics, and other standard physiological and ecological measurements which, as data collection proceeded over several years, would present an increasingly challenging target for next generation models.

Cooperative angle-only orbit initialization via fusion of admissible areas

NASA Astrophysics Data System (ADS)

Jia, Bin; Pham, Khanh; Blasch, Erik; Chen, Genshe; Shen, Dan; Wang, Zhonghai

2017-05-01

For the short-arc angle only orbit initialization problem, the admissible area is often used. However, the accuracy using a single sensor is often limited. For high value space objects, it is desired to achieve more accurate results. Fortunately, multiple sensors, which are dedicated to space situational awareness, are available. The work in this paper uses multiple sensors' information to cooperatively initialize the orbit based on the fusion of multiple admissible areas. Both the centralized fusion and decentralized fusion are discussed. Simulation results verify the expectation that the orbit initialization accuracy is improved by using information from multiple sensors.

76 FR 66698 - Postsecondary Educational Institutions Invited To Participate in Experiments Under the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

... Experiments Under the Experimental Sites Initiative AGENCY: Office of Postsecondary Education, Department of... institutions to participate in experiments under the Experimental Sites Initiative. SUMMARY: The Secretary... participate in one or more new experiments under the Experimental Sites Initiative (ESI), as authorized by...

In vitro transcription in the presence of DNA oligonucleotides can generate strong anomalous initiation sites.

PubMed

Chow, C W; Clark, M P; Rinaldo, J E; Chalkley, R

1996-03-01

In the present study, we have explored an unexpected observation in transcription initiation that is mediated by single-stranded oligonucleotides. Initially, our goal was to understand the function of different upstream regulatory elements/initiation sites in the rat xanthine dehydrogenase/oxidase (XDH/XO) promoter. We performed in vitro transcription with HeLa nuclear extracts in the presence of different double-stranded oligonucleotides against upstream elements as competitors. A new and unusual transcription initiation site was detected by primer extension. This new initiation site maps to the downstream region of the corresponding competitor. Subsequent analyses have indicated that the induction of a new transcription initiation site is anomalous which is due to the presence of a small amount of single-stranded oligonucleotide in the competitor. We found that this anomalous initiation site is insensitive to the orientation of the promoter and requires only a small amount of single-stranded oligonucleotide (< 2-fold molar excess relative to template). We surmise that a complementary interaction between the single-stranded oligonucleotide and transiently denatured promoter template may be responsible for this sequence-specific transcription initiation artifact. To study the regulation of transcription initiation by in vitro transcription approaches, we propose that one should probe the effect of removing transacting factors by adding an excess of a cognate oligonucleotide which does not bear exact sequence identity to the template.

Effect of the sequence data deluge on the performance of methods for detecting protein functional residues.

PubMed

Garrido-Martín, Diego; Pazos, Florencio

2018-02-27

The exponential accumulation of new sequences in public databases is expected to improve the performance of all the approaches for predicting protein structural and functional features. Nevertheless, this was never assessed or quantified for some widely used methodologies, such as those aimed at detecting functional sites and functional subfamilies in protein multiple sequence alignments. Using raw protein sequences as only input, these approaches can detect fully conserved positions, as well as those with a family-dependent conservation pattern. Both types of residues are routinely used as predictors of functional sites and, consequently, understanding how the sequence content of the databases affects them is relevant and timely. In this work we evaluate how the growth and change with time in the content of sequence databases affect five sequence-based approaches for detecting functional sites and subfamilies. We do that by recreating historical versions of the multiple sequence alignments that would have been obtained in the past based on the database contents at different time points, covering a period of 20 years. Applying the methods to these historical alignments allows quantifying the temporal variation in their performance. Our results show that the number of families to which these methods can be applied sharply increases with time, while their ability to detect potentially functional residues remains almost constant. These results are informative for the methods' developers and final users, and may have implications in the design of new sequencing initiatives.

Gastrointestinal anthrax after an animal-hide drumming event - New Hampshire and Massachusetts, 2009.

PubMed

2010-07-23

On December 24, 2009, a woman aged 24 years from New Hampshire was confirmed to have gastrointestinal anthrax on the basis of clinical findings and a Bacillus anthracis blood culture isolate. Her symptoms began on December 5. One day before symptom onset, she had participated in a drumming event at a community organization's building where animal-hide drums of multiple ages and origins were played. This report describes the case and subsequent investigation, which identified 84 persons potentially exposed to anthrax, including those persons at the drumming event and those who lived or worked at the event site. Review of New Hampshire disease surveillance data and clinical microbiology records for periods before and after the event identified no additional anthrax cases. Initial qualitative environmental testing of the event site yielded three positive samples (two from drum heads and one composite sample of three electrical outlets in the main drumming room). Wider, targeted, semi-quantitative environmental testing of the site and additional drums yielded six positive samples (two from one drum and four from environmental locations in the building). These results suggested that aerosolization of spores from drumheads had occurred. All isolates obtained from environmental and drum samples matched the patient's isolate by multiple-locus variable-number tandem repeat analysis using eight loci (MLVA-8). Public health agencies and persons with exposure to animal-hide drums should be aware of the potential, although remote, risk for anthrax exposure associated with these drums.

Differential Binding Models for Direct and Reverse Isothermal Titration Calorimetry.

PubMed

Herrera, Isaac; Winnik, Mitchell A

2016-03-10

Isothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659-8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume-normalized heat signal (δQ(V) = δq/dV) of direct and reverse calorimetry titrations. Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal-ligand pairs studied.

Central institutional review board review for an academic trial network.

PubMed

Kaufmann, Petra; O'Rourke, P Pearl

2015-03-01

Translating discoveries into therapeutics is often delayed by lengthy start-up periods for multicenter clinical trials. One cause of delay can be multiple institutional review board (IRB) reviews of the same protocol. When developing the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT; hereafter, NN), the National Institute of Neurological Disorders and Stroke (NINDS) established a central IRB (CIRB) based at Massachusetts General Hospital, the academic medical center that received the NN clinical coordinating center grant. The 25 NN sites, located at U.S. academic institutions, agreed to required CIRB use for NN trials. To delineate roles and establish legal relationships between the NN sites and the CIRB, the CIRB executed reliance agreements with the sites and their affiliates that hold federalwide assurance for the protection of human subjects (FWA); this took, on average, 84 days. The first NN protocol reviewed by the CIRB achieved full approval to allow participant enrollment within 56 days and went from grant award to the first patient visit in less than four months. The authors describe anticipated challenges related to institutional oversight responsibilities versus regulatory CIRB review as well as unanticipated challenges related to working with complex organizations that include multiple FWA-holding affiliates. The authors anticipate that CIRB use will decrease NN trial start-up time and thus promote efficient trial implementation. They plan to collect data on timelines and costs associated with CIRB use. The NINDS plans to promote CIRB use in future initiatives.

Airborne Lidar Measurements of Surface Topography and Structure in Arctic-Boreal Ecosystems

NASA Astrophysics Data System (ADS)

Hofton, M. A.; Blair, J. B.; Rabine, D.; Cornejo, H.; Story, S.

2017-12-01

In June-July 2017, NASA's Land, Vegetation and Ice Sensor (LVIS) Facility was deployed to sites in northern Canada and Alaska as part of NASA's Arctic-Boreal Vulnerability Experiment (ABoVE) 2017 airborne campaign. ABoVE is a large-scale, multi-year study of environmental change and its implications for social-ecological systems, and involves multiple airborne sensors flying both field-based and larger scale sampling sites. During the 4 week deployment of LVIS-F, a total of 15 flights were flown over diverse science targets based out of multiple airports in Canada and Alaska. LVIS-F is NASA's high-altitude airborne lidar sensor, collecting a nominal 2km wide swath of data from 10km altitude above the ground. Footprints are continguous both along and across track and for ABoVE operations, were 6m in diameter. Full waveform data are collected for every footprint and georeferenced to provide a true 3 dimensional view of overflown terrain. Along with precise positioning and pointing information, the LVIS laser range and waveform data are processed to provide high-quality measurements of surface structure including ground elevation, canopy height and canopy volume metrics. Information on data coverage and examples of level1b and level2 data products at science target sites will be shown along with initial results for data precision and accuracy. All AboVe LVIS data products will be available to investigators via a NASA DAAC.

Sarcocystis neurona encephalitis in a dog.

PubMed

Cooley, A J; Barr, B; Rejmanek, D

2007-11-01

A 1.5-year-old male Feist dog was presented to a veterinarian for reluctance to stand on the hind legs. Treatment included dexamethasone and resulted in a favorable initial response, but posterior paresis returned and progressed to recumbency, hyperesthesia, and attempts to bite the owner. The dog was euthanized. The brain was negative for rabies by fluorescent antibody analysis. Multiple foci of encephalitis were found in the cerebrum and particularly in the cerebellum. Protozoa morphologically consistent with Sarcocystis sp. were identified at sites of intense inflammation and malacia. Additionally, multiple schizonts were identified in areas without inflammation. Immunohistochemistry using both polyclonal and monoclonal antibodies specific for Sarcocystis neurona was strongly positive. No reaction to polyclonal antisera for Toxoplasma gondii or Neospora caninum was found. Polymerase chain reaction confirmed that the protozoa were S. neurona. Additional aberrant hosts for S. neurona other than horses have been identified, but S. neurona encephalitis has not been documented previously in the dog.

A model for making project funding decisions at the National Cancer Institute.

PubMed

Hall, N G; Hershey, J C; Kessler, L G; Stotts, R C

1992-01-01

This paper describes the development of a model for making project funding decisions at The National Cancer Institute (NCI). The American Stop Smoking Intervention Study (ASSIST) is a multiple-year, multiple-site demonstration project, aimed at reducing smoking prevalence. The initial request for ASSIST proposals was answered by about twice as many states as could be funded. Scientific peer review of the proposals was the primary criterion used for funding decisions. However, a modified Delphi process made explicit several criteria of secondary importance. A structured questionnaire identified the relative importance of these secondary criteria, some of which we incorporated into a composite preference function. We modeled the proposal funding decision as a zero-one program, and adjusted the preference function and available budget parametrically to generate many suitable outcomes. The actual funding decision, identified by our model, offers significant advantages over manually generated solutions found by experts at NCI.

The FORE-SCE model: a practical approach for projecting land cover change using scenario-based modeling

USGS Publications Warehouse

Sohl, Terry L.; Sayler, Kristi L.; Drummond, Mark A.; Loveland, Thomas R.

2007-01-01

A wide variety of ecological applications require spatially explicit, historic, current, and projected land use and land cover data. The U.S. Land Cover Trends project is analyzing contemporary (1973–2000) land-cover change in the conterminous United States. The newly developed FORE-SCE model used Land Cover Trends data and theoretical, statistical, and deterministic modeling techniques to project future land cover change through 2020 for multiple plausible scenarios. Projected proportions of future land use were initially developed, and then sited on the lands with the highest potential for supporting that land use and land cover using a statistically based stochastic allocation procedure. Three scenarios of 2020 land cover were mapped for the western Great Plains in the US. The model provided realistic, high-resolution, scenario-based land-cover products suitable for multiple applications, including studies of climate and weather variability, carbon dynamics, and regional hydrology.

Electric properties and carrier multiplication in breakdown sites in multi-crystalline silicon solar cells

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

Schneemann, Matthias; Carius, Reinhard; Rau, Uwe

2015-05-28

This paper studies the effective electrical size and carrier multiplication of breakdown sites in multi-crystalline silicon solar cells. The local series resistance limits the current of each breakdown site and is thereby linearizing the current-voltage characteristic. This fact allows the estimation of the effective electrical diameters to be as low as 100 nm. Using a laser beam induced current (LBIC) measurement with a high spatial resolution, we find carrier multiplication factors on the order of 30 (Zener-type breakdown) and 100 (avalanche breakdown) as new lower limits. Hence, we prove that also the so-called Zener-type breakdown is followed by avalanche multiplication. Wemore » explain that previous measurements of the carrier multiplication using thermography yield results higher than unity, only if the spatial defect density is high enough, and the illumination intensity is lower than what was used for the LBIC method. The individual series resistances of the breakdown sites limit the current through these breakdown sites. Therefore, the measured multiplication factors depend on the applied voltage as well as on the injected photocurrent. Both dependencies are successfully simulated using a series-resistance-limited diode model.« less

Dirigent proteins and dirigent sites in lignifying tissues

NASA Technical Reports Server (NTRS)

Burlat, V.; Kwon, M.; Davin, L. B.; Lewis, N. G.

2001-01-01

Tissue-specific dirigent protein gene expression and associated dirigent (site) localization were examined in various organs of Forsythia intermedia using tissue printing, in situ mRNA hybridization and immunolabeling techniques, respectively. Dirigent protein gene expression was primarily noted in the undifferentiated cambial regions of stem sections, whereas dirigent protein sites were detected mainly in the vascular cambium and ray parenchyma cell initials. Immunolocalization also revealed cross-reactivity with particular regions of the lignified cell walls, these being coincident with the known sites of initiation of lignin deposition. These latter regions are considered to harbor contiguous arrays of dirigent (monomer binding) sites for initiation of lignin biopolymer assembly. Dirigent protein mRNA expression was also localized in the vascular regions of roots and petioles, whereas in leaves the dirigent sites were primarily associated with the palisade layers and the vascular bundle. That is, dirigent protein mediated lignan biosynthesis was initiated primarily in the cambium and ray cell initial regions of stems as well as in the leaf palisade layers, this being in accordance with the occurrence of the lignans for defense purposes. Within lignified secondary xylem cell walls, however, dirigent sites were primarily localized in the S(1) sublayer and compound middle lamella, these being coincident with previously established sites for initiation of macromolecular lignin biosynthesis. Once initiation occurs, lignification is proposed to continue through template polymerization.

Relook TURBT in superficial bladder cancer: its importance and its correlation with the tumor ploidy.

PubMed

Dwivedi, Udai S; Kumar, Abhay; Das, Suren K; Trivedi, Sameer; Kumar, Mohan; Sunder, Shyam; Singh, Pratap B

2009-01-01

To evaluate various prognostic factor predictors of residual growth in Relook transurethral resection of bladder tumor (TURBT) in superficial bladder cancer. Also, to evaluate the role of Relook TURBT along with the ploidy for prediction of recurrence and stage progression in these patients. Fifty patients with superficial bladder cancer underwent TURBT after complete evaluation. Ploidy of the tumor specimen was evaluated by flow cytometry. After 4 to 6 weeks of initial TURBT, these patients underwent Relook TURBT. Final treatment was given after the results of the histological evaluation of these specimens. Patients who underwent bladder sparing treatment were followed-up. Of the patients, 28.5% had residual tumor in Relook TURBT. Growth was found to be at the same site in 66.7% and at a different site 33.3%; 75% had single while 25% had multiple residual growth. Residual malignant tissue had a statistically significant correlation with size of the tumor (>3 cm), appearance (solid tumor), number (>3), grade (high), and multiple previous resections. Overall, the up-migration of stage and grade leads to change in treatment in 41.6%; 5 underwent radical cystectomy and 1 opted for radiotherapy; in 2 patients, intravesical BCG was given. In follow-up of mean 11.5 months, 16.6% had recurrence. Presence of residual growth in Relook TURBT along with number, size, morphology, and multiple previous resections were found to have significant correlation with the recurrence in these patients. Ploidy and grade of the tumor were not found to have correlation. Multiple, more than 3 cm, solid high grade tumor with > 3 previous resections were predictors of presence of residual tumor in Relook TURBT. Presence of residual growth is a significant risk factor for recurrence. Ploidy was not found to be significantly correlated with recurrence.

High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

PubMed Central

Tutterrow, Yeung L.; Avril, Marion; Singh, Kavita; Long, Carole A.; Leke, Robert J.; Sama, Grace; Salanti, Ali; Smith, Joseph D.; Leke, Rose G. F.

2012-01-01

Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity. PMID:22331427

EPA True NO2 ground site measurements ?? multiple sites, TCEQ ground site measurements of meteorological and air pollution parameters ?? multiple sites ,GeoTASO NO2 Vertical Column

EPA Pesticide Factsheets

EPA True NO2 ground site measurements ?? multiple sites - http://www-air.larc.nasa.gov/cgi-bin/ArcView/discover-aq.tx-2013; TCEQ ground site measurements of meteorological and air pollution parameters ?? multiple sites - http://www-air.larc.nasa.gov/cgi-bin/ArcView/discover-aq.tx-2013; GeoTASO NO2 Vertical Column - http://www-air.larc.nasa.gov/cgi-bin/ArcView/discover-aq.tx-2013?FALCON=1This dataset is associated with the following publication:Nowlan, C., X. Lu, J. Leitch, K. Chance, G. González Abad, C. Lu, P. Zoogman, J. Cole, T. Delker, W. Good, F. Murcray, L. Ruppert, D. Soo, M. Follette-Cook, S. Janz, M. Kowalewski, C. Loughner, K. Pickering, J. Herman, M. Beaver, R. Long, J. Szykman, L. Judd, P. Kelley, W. Luke, X. Ren, and J. Al-Saadi. Nitrogen dioxide observations from the Geostationary Trace gas and Aerosol Sensor Optimization (GeoTASO) airborne instrument: Retrieval algorithm and measurements during DISCOVER-AQ Texas 2013. Atmospheric Measurement Techniques. Copernicus Publications, Katlenburg-Lindau, GERMANY, 9(6): 2647-2668, (2016).

The site of primary T cell activation is a determinant of the balance between intrahepatic tolerance and immunity.

PubMed

Bowen, David G; Zen, Monica; Holz, Lauren; Davis, Thomas; McCaughan, Geoffrey W; Bertolino, Patrick

2004-09-01

Hepatic immunobiology is paradoxical: although the liver possesses unusual tolerogenic properties, it is also the site of effective immune responses against multiple pathogens and subject to immune-mediated pathology. The mechanisms underlying this dichotomy remain unclear. Following previous work demonstrating that the liver may act as a site of primary T cell activation, we demonstrate here that the balance between immunity and tolerance in this organ is established by competition for primary activation of CD8+ T cells between the liver and secondary lymphoid tissues, with the immune outcome determined by the initial site of activation. Using a transgenic mouse model in which antigen is expressed within both liver and lymph nodes, we show that while naive CD8+ T cells activated within the lymph nodes were capable of mediating hepatitis, cells undergoing primary activation within the liver exhibited defective cytotoxic function and shortened half-life and did not mediate hepatocellular injury. The implications of these novel findings may pertain not only to the normal maintenance of peripheral tolerance, but also to hepatic allograft tolerance and the immunopathogenesis of chronic viral hepatitis.

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

Robichaud, R.; Fields, J.; Roberts, J. O.

The U.S. Environmental Protection Agency (EPA) launched the RE-Powering America's Land initiative to encourage development of renewable energy (RE) on potentially contaminated land and mine sites. EPA is collaborating with the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) to evaluate RE options at Naval Station (NAVSTA) Newport in Newport, Rhode Island where multiple contaminated areas pose a threat to human health and the environment. Designated a superfund site on the National Priorities List in 1989, the base is committed to working toward reducing the its dependency on fossil fuels, decreasing its carbon footprint, and implementing RE projectsmore » where feasible. The Naval Facilities Engineering Service Center (NFESC) partnered with NREL in February 2009 to investigate the potential for wind energy generation at a number of Naval and Marine bases on the East Coast. NAVSTA Newport was one of several bases chosen for a detailed, site-specific wind resource investigation. NAVSTA Newport, in conjunction with NREL and NFESC, has been actively engaged in assessing the wind resource through several ongoing efforts. This report focuses on the wind resource assessment, the estimated energy production of wind turbines, and a survey of potential wind turbine options based upon the site-specific wind resource.« less

Use of the 2010 McDonald criteria can facilitate early diagnosis of pediatric multiple sclerosis in a predominantly black cohort.

PubMed

Williams, Mitchel T; Tapos, Daniela O; Juhász, Csaba

2014-12-01

Pediatric-onset multiple sclerosis represents around 3-5% of all patients with multiple sclerosis. Both the 2005 and 2010 McDonald criteria for multiple sclerosis have been suggested for the possible use in pediatric-onset multiple sclerosis. Modifications incorporated into the 2010 criteria enabled the fulfillment of dissemination in time to be met with the initial magnetic resonance imaging. The present study was designed to compare the diagnostic sensitivity of these criteria at initial presentation, the time to fulfilling them, and secondary effects of ethnicity in pediatric-onset multiple sclerosis. Twenty-five children with clinically definite multiple sclerosis (mean age, 14.6 ± 3.1 years; 15 girls) from a single center between 2005 and 2012 were analyzed using both the 2005 and 2010 McDonald criteria based on initial clinical presentation and neuroimaging findings comparing diagnostic sensitivity, time interval to meet diagnosis, and ethnicity. Initial multiple sclerosis diagnosis rates applying the 2005 McDonald criteria were 32% compared with 92% for the 2010 criteria (P = 0.0003). The mean time after initial signs until the 2005 and 2010 McDonald criteria for multiple sclerosis were met was 5.0 vs 0.7 months, respectively (P = 0.001). Time to diagnosis using the 2010 criteria was shorter in black children than the European white (P = 0.005). The 2010 McDonald criteria are an appropriate tool for the timely diagnosis of pediatric multiple sclerosis, especially in black children, potentially allowing an earlier initiation of disease-modifying therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantitative evidence for the benefits of Moving the Goalposts, a Sport for Development project in rural Kenya.

PubMed

Woodcock, Alison; Cronin, Órla; Forde, Sarah

2012-08-01

Sport for Development has many reported benefits, but quantitative evidence of the impact of these interventions in Low Income Countries remains sparse. A new monitoring and evaluation toolkit was used in a cross-sectional survey at Moving the Goalposts (MTG), a football project aiming to empower young Kenyan women. We wished to determine empirically whether increased membership duration brought increased benefits. MTG selected and translated toolkit items consistent with the organisation's strategic aims. We collected 333 completed questionnaires at 15 sites. Psychometric validation revealed some reliable scales; remaining items were scored separately. Scores were sensitive to differences between members defined by sociodemographic and site characteristics. Bivariate and multiple regression analyses showed that increased membership duration brought increasing benefits across several domains (perceived lifeskills; social life; insights about HIV/AIDS; outcomes related to female empowerment). Improved leadership skills were mainly age-related. Members attending more established sites experienced greater benefits, but members at more and less accessible sites benefitted similarly. Positive thoughts and feelings were related not to membership duration, but to how long a site had been operating. This indicates the importance of creating a positive culture over time. This cross-sectional study provides quantitative evidence for the benefits of Sport for Development initiatives. Copyright © 2012 Elsevier Ltd. All rights reserved.

Habitat stress initiates changes in composition, CO2 gas exchange and C-allocation as life traits in biological soil crusts.

PubMed

Colesie, Claudia; Green, T G Allan; Haferkamp, Ilka; Büdel, Burkhard

2014-10-01

Biological soil crusts (BSC) are the dominant functional vegetation unit in some of the harshest habitats in the world. We assessed BSC response to stress through changes in biotic composition, CO2 gas exchange and carbon allocation in three lichen-dominated BSC from habitats with different stress levels, two more extreme sites in Antarctica and one moderate site in Germany. Maximal net photosynthesis (NP) was identical, whereas the water content to achieve maximal NP was substantially lower in the Antarctic sites, this apparently being achieved by changes in biomass allocation. Optimal NP temperatures reflected local climate. The Antarctic BSC allocated fixed carbon (tracked using (14)CO2) mostly to the alcohol soluble pool (low-molecular weight sugars, sugar alcohols), which has an important role in desiccation and freezing resistance and antioxidant protection. In contrast, BSC at the moderate site showed greater carbon allocation into the polysaccharide pool, indicating a tendency towards growth. The results indicate that the BSC of the more stressed Antarctic sites emphasise survival rather than growth. Changes in BSC are adaptive and at multiple levels and we identify benefits and risks attached to changing life traits, as well as describing the ecophysiological mechanisms that underlie them.

Pathophysiologically based drug treatment of sickle cell disease.

PubMed

Steinberg, Martin H

2006-04-01

Sickle cell disease is a systemic disorder that is caused by a mutation (Glu6Val) in the gene that encodes beta globin. The sickle hemoglobin molecule (HbS) is a tetramer of two alpha-globin chains and two sickle beta-globin chains, and has the tendency to polymerize when deoxygenated. HbS facilitates abnormal interactions between the sickle erythrocyte and leukocytes and endothelial cells, which trigger a complex pathobiology. This multifaceted pathophysiology provides the opportunity to interrupt the disease at multiple sites, including polymerization of HbS, erythrocyte density and cell-cell interactions. For example, it is possible to induce higher concentrations of fetal hemoglobin, which disrupts the pathology-initiating step of HbS polymerization. Furthermore, it is possible to improve the hydration of sickle erythrocytes and it might be feasible to counteract the endothelial, inflammatory and oxidative abnormalities of sickle cell disease. A therapeutic approach that targets several sites of pathobiology might be most promising.

Effects of community-based, videotape, and flash card instruction of community-referenced sight words on students with mental retardation.

PubMed Central

Cuvo, A J; Klatt, K P

1992-01-01

Community-referenced sight words and phrases were taught to adolescents with mild and moderate mental retardation using three instructional methods in two locations. Words were presented on flash cards in a school setting, on videotape recordings in a school setting, and on naturally occurring signs in the community. During each session, participants were taught one third of the words in each of these conditions and were then tested at the community sites. A constant prompt delay procedure was used to promote stimulus control to the experimenter's cue initially and then to transfer control to the textual stimuli used for training. A multiple baseline across participants design was employed. Results showed rapid acquisition of the community-referenced sight words in all three training conditions and generalization from the flash card and videotape conditions to the community sites. PMID:1378827

Engineering a horseradish peroxidase C stable to radical attacks by mutating multiple radical coupling sites.

PubMed

Kim, Su Jin; Joo, Jeong Chan; Song, Bong Keun; Yoo, Young Je; Kim, Yong Hwan

2015-04-01

Peroxidases have great potential as industrial biocatalysts. In particular, the oxidative polymerization of phenolic compounds catalyzed by peroxidases has been extensively examined because of the advantage of this method over other conventional chemical methods. However, the industrial application of peroxidases is often limited because of their rapid inactivation by phenoxyl radicals during oxidative polymerization. In this work, we report a novel protein engineering approach to improve the radical stability of horseradish peroxidase isozyme C (HRPC). Phenylalanine residues that are vulnerable to modification by the phenoxyl radicals were identified using mass spectrometry analysis. UV-Vis and CD spectra showed that radical coupling did not change the secondary structure or the active site of HRPC. Four phenylalanine (Phe) residues (F68, F142, F143, and F179) were each mutated to alanine residues to generate single mutants to examine the role of these sites in radical coupling. Despite marginal improvement of radical stability, each single mutant still exhibited rapid radical inactivation. To further reduce inactivation by radical coupling, the four substitution mutations were combined in F68A/F142A/F143A/F179A. This mutant demonstrated dramatic enhancement of radical stability by retaining 41% of its initial activity compared to the wild-type, which was completely inactivated. Structure and sequence alignment revealed that radical-vulnerable Phe residues of HPRC are conserved in homologous peroxidases, which showed the same rapid inactivation tendency as HRPC. Based on our site-directed mutagenesis and biochemical characterization, we have shown that engineering radical-vulnerable residues to eliminate multiple radical coupling can be a good strategy to improve the stability of peroxidases against radical attack. © 2014 Wiley Periodicals, Inc.

Case-control analysis in highway safety: Accounting for sites with multiple crashes.

PubMed

Gross, Frank

2013-12-01

There is an increased interest in the use of epidemiological methods in highway safety analysis. The case-control and cohort methods are commonly used in the epidemiological field to identify risk factors and quantify the risk or odds of disease given certain characteristics and factors related to an individual. This same concept can be applied to highway safety where the entity of interest is a roadway segment or intersection (rather than a person) and the risk factors of interest are the operational and geometric characteristics of a given roadway. One criticism of the use of these methods in highway safety is that they have not accounted for the difference between sites with single and multiple crashes. In the medical field, a disease either occurs or it does not; multiple occurrences are generally not an issue. In the highway safety field, it is necessary to evaluate the safety of a given site while accounting for multiple crashes. Otherwise, the analysis may underestimate the safety effects of a given factor. This paper explores the use of the case-control method in highway safety and two variations to account for sites with multiple crashes. Specifically, the paper presents two alternative methods for defining cases in a case-control study and compares the results in a case study. The first alternative defines a separate case for each crash in a given study period, thereby increasing the weight of the associated roadway characteristics in the analysis. The second alternative defines entire crash categories as cases (sites with one crash, sites with two crashes, etc.) and analyzes each group separately in comparison to sites with no crashes. The results are also compared to a "typical" case-control application, where the cases are simply defined as any entity that experiences at least one crash and controls are those entities without a crash in a given period. In a "typical" case-control design, the attributes associated with single-crash segments are weighted the same as the attributes of segments with multiple crashes. The results support the hypothesis that the "typical" case-control design may underestimate the safety effects of a given factor compared to methods that account for sites with multiple crashes. Compared to the first alternative case definition (where multiple crash segments represent multiple cases) the results from the "typical" case-control design are less pronounced (i.e., closer to unity). The second alternative (where case definitions are constructed for various crash categories and analyzed separately) provides further evidence that sites with single and multiple crashes should not be grouped together in a case-control analysis. This paper indicates a clear need to differentiate sites with single and multiple crashes in a case-control analysis. While the results suggest that sites with multiple crashes can be accounted for using a case-control design, further research is needed to determine the optimal method for addressing this issue. This paper provides a starting point for that research. Copyright © 2012 Elsevier Ltd. All rights reserved.

Multiple double cross-section transmission electron microscope sample preparation of specific sub-10 nm diameter Si nanowire devices.

PubMed

Gignac, Lynne M; Mittal, Surbhi; Bangsaruntip, Sarunya; Cohen, Guy M; Sleight, Jeffrey W

2011-12-01

The ability to prepare multiple cross-section transmission electron microscope (XTEM) samples from one XTEM sample of specific sub-10 nm features was demonstrated. Sub-10 nm diameter Si nanowire (NW) devices were initially cross-sectioned using a dual-beam focused ion beam system in a direction running parallel to the device channel. From this XTEM sample, both low- and high-resolution transmission electron microscope (TEM) images were obtained from six separate, specific site Si NW devices. The XTEM sample was then re-sectioned in four separate locations in a direction perpendicular to the device channel: 90° from the original XTEM sample direction. Three of the four XTEM samples were successfully sectioned in the gate region of the device. From these three samples, low- and high-resolution TEM images of the Si NW were taken and measurements of the NW diameters were obtained. This technique demonstrated the ability to obtain high-resolution TEM images in directions 90° from one another of multiple, specific sub-10 nm features that were spaced 1.1 μm apart.

Non-active site mutation (Q123A) in New Delhi metallo-β-lactamase (NDM-1) enhanced its enzyme activity.

PubMed

Ali, Abid; Azam, Mohd W; Khan, Asad U

2018-06-01

New Delhi metallo β-lactamase-1 is one of the carbapenemases, causing hydrolysis of almost all β-lactamase antibiotics. Seventeen different NDM variants have been reported so far, they varied in their sequences either by single or multiple amino acid substitutions. Hence, it is important to understand its structural and functional relation. In the earlier studies role of active site residues has been studied but non-active site residues has not studied in detail. Therefore, we have initiated to further comprehend its structure and function relation by mutating some of its non-active site residues. A laboratory mutant of NDM-1 was generated by PCR-based site-directed mutagenesis, replacing Q to A at 123 position. The MICs of imipenem and meropenem for NDM-1 Q123A were found increased by 2 fold as compare to wild type and so the hydrolytic activity was enhanced (Kcat/Km) as compared to NDM-1 wild type. GOLD fitness scores were also found in favour of kinetics data. Secondary structure for α-helical content was determined by Far-UV circular dichroism (CD), which showed significant conformational changes. We conclude a noteworthy role of non-active-site amino acid residues in the catalytic activity of NDM-1. This study also provides an insight of emergence of new variants through natural evolution. Copyright © 2018 Elsevier B.V. All rights reserved.

Loss of Hda activity stimulates replication initiation from I-box, but not R4 mutant origins in Escherichia coli.

PubMed

Riber, Leise; Fujimitsu, Kazuyuki; Katayama, Tsutomu; Løbner-Olesen, Anders

2009-01-01

Initiation of chromosome replication in Escherichia coli is limited by the initiator protein DnaA associated with ATP. Within the replication origin, binding sites for DnaA associated with ATP or ADP (R boxes) and the DnaA(ATP) specific sites (I-boxes, tau-boxes and 6-mer sites) are found. We analysed chromosome replication of cells carrying mutations in conserved regions of oriC. Cells carrying mutations in DnaA-boxes I2, I3, R2, R3 and R5 as well as FIS and IHF binding sites resembled wild-type cells with respect to origin concentration. Initiation of replication in these mutants occurred in synchrony or with slight asynchrony only. Furthermore, lack of Hda stimulated initiation in all these mutants. The DnaA(ATP) containing complex that leads to initiation can therefore be formed in the absence of several of the origin DnaA binding sites including both DnaA(ATP) specific I-boxes. However, competition between I-box mutant and wild-type origins, revealed a positive role of I-boxes on initiation. On the other hand, mutations affecting DnaA-box R4 were found to be compromised for initiation and could not be augmented by an increase in cellular DnaA(ATP)/DnaA(ADP) ratio. Compared with the sites tested here, R4 therefore seems to contribute to initiation most critically.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

PubMed

Bendaly, Edmond; Dalal, Anand A; Culver, Kenneth; Galebach, Philip; Bocharova, Iryna; Foster, Rebekah; Sasane, Medha; Macalalad, Alexander R; Guérin, Annie

2017-05-01

This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. Novartis Pharmaceutical Corporation.

Installation of multiple automated external defibrillators to prevent sudden death in school-aged children.

PubMed

Higaki, Takashi; Chisaka, Toshiyuki; Moritani, Tomozo; Ohta, Masaaki; Takata, Hidemi; Yamauchi, Toshifumi; Yamaguchi, Youhei; Konishi, Kyoko; Yamamoto, Eiichi; Ochi, Fumihiro; Eguchi, Mariko; Eguchi-Ishimae, Minenori; Mitani, Yoshihide; Ishii, Eiichi

2016-12-01

Recently, a student died of idiopathic ventricular fibrillation in a school where an automated external defibrillator (AED) had been installed. The tragedy could not be prevented because the only AED in the school was installed in the teachers' office, far from the school ground where the accident took place. This prompted establishment of a multiple AED system in schools. The aim of this study was to analyze the efficacy of the multiple AED system to prevent sudden death in school-aged children. Assumed accident sites consisted of the school ground, gymnasium, Judo and Kendo hall, swimming pool, and classrooms on the first and the fourth floor. Multiple AED were installed in the teachers' office, gymnasium, some classrooms, and also provided as a portable AED in a rucksack. The time from the accident site to the teachers' office for single AED, and from the accident site to the nearest AED for multiple AED, was calculated. The AED retrieval time was significantly shorter in 55 elementary schools and in 29 junior high schools when multiple AED were installed compared with single AED. Except for the classroom on the fourth floor, the number of people who took >120 s to bring the AED to the accident site was lower when multiple AED were installed compared with the single AED. Multiple AED provided in appropriate sites can reduce the time to reach the casualty and hence prevent sudden death in school-aged children. © 2016 Japan Pediatric Society.

Overview of Research Transition Products

NASA Technical Reports Server (NTRS)

Robinson, John

2014-01-01

Demonstrate increased, more consistent use of Performance- Based Navigation (PBN). Accelerate transfer of NASA scheduling and spacing technologies for inclusion in late mid-term NAS. During high-fidelity human-in-the-loop simulations of Terminal Sequencing and Spacing, air traffic controllers have significantly improved their use of PBN procedures during busy traffic periods without increased workload. Executed an aggressive, short timeframe development schedule. Developed TSS prototype based upon FAA operational systems. Conducted multiple joint FAA/NASA human-in-the-loop simulations. Performed repeated incremental deliveries of tech transfer material to non-traditional RTT stakeholders. Will continue to participate in later phases of FAA acquisition process. ATD-1 transferred Terminal Sequencing and Spacing (TSS) technologies to the FAA. TSS enables routine use of underutilized advanced avionics and PBN procedures. Potential benefits to airlines operating at initial TSS sites estimated to be $300-400M/year. FAA is planning for an initial capability in the NAS in 2018.

Differential distribution of voltage-gated ion channels in cortical neurons: implications for epilepsy.

PubMed

Child, Nicholas D; Benarroch, Eduardo E

2014-03-18

Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

Scleroderma Autoantigens Are Uniquely Fragmented by Metal-catalyzed Oxidation Reactions: Implications for Pathogenesis

PubMed Central

Casciola-Rosen, Livia; Wigley, Fredrick; Rosen, Antony

1997-01-01

The observation that revelation of immunocryptic epitopes in self antigens may initiate the autoimmune response has prompted the search for processes which induce novel fragmentation of autoantigens as potential initiators of autoimmunity. The reversible ischemia reperfusion which characterizes scleroderma has focused attention on reactive oxygen species as molecules which might induce autoantigen fragmentation. We demonstrate that several of the autoantigens targeted in diffuse scleroderma are uniquely susceptible to cleavage by reactive oxygen species, in a metal-dependent manner. Multiple features of the fragmentation reaction and its inhibition indicate that these autoantigens possess metal-binding sites, which focus metal-catalyzed oxidation reactions (and consequent fragmentation) to specific regions of the antigens. These data suggest that the autoantibody response in scleroderma is the immune marker of unique protein fragmentation, induced by ischemia reperfusion in the presence of appropriate metals, and focus attention on abnormal metal status as a potential pathogenic principle in this disease. PMID:8996243

Multi-Sensor Characterization of the Boreal Forest: Initial Findings

NASA Technical Reports Server (NTRS)

Reith, Ernest; Roberts, Dar A.; Prentiss, Dylan

2001-01-01

Results are presented in an initial apriori knowledge approach toward using complementary multi-sensor multi-temporal imagery in characterizing vegetated landscapes over a site in the Boreal Ecosystem-Atmosphere Study (BOREAS). Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) and Airborne Synthetic Aperture Radar (AIRSAR) data were segmented using multiple endmember spectral mixture analysis and binary decision tree approaches. Individual date/sensor land cover maps had overall accuracies between 55.0% - 69.8%. The best eight land cover layers from all dates and sensors correctly characterized 79.3% of the cover types. An overlay approach was used to create a final land cover map. An overall accuracy of 71.3% was achieved in this multi-sensor approach, a 1.5% improvement over our most accurate single scene technique, but 8% less than the original input. Black spruce was evaluated to be particularly undermapped in the final map possibly because it was also contained within jack pine and muskeg land coverages.

Influence of microstructure on the fretting resistance of Al-Cu-Li alloys

NASA Astrophysics Data System (ADS)

Delacroix, Jessica; Cazottes, Sophie; Daniélou, Armelle; Fouvry, Siegfried; Buffiere, Jean-Yves

The resistance of two Al-Cu-Li alloys (2050 and 2196) to fretting has been investigated. For each material two heat treatments have been studied (T8 and low temperature ageing). Fretting tests with a cylinder-plane configuration have been performed in the partial slip regime. The results obtained show that the low temperature temper gives a better resistance to fretting crack initiation and propagation than the T8 temper for both alloys. The 3D shape of the fretting cracks has been observed by high resolution synchrotron X-ray tomography. Multiple initiation sites were observed below the contact. In their early stages of development, the fretting cracks grow approximately radially within the material leading to thumb nail cracks which eventually merge laterally. The difference in fretting resistance is analysed with respect to the 3D fracture surface of the fretting cracks in relation with the alloys precipitation state.

Scheduling the Remediation of Port Hope: Logistical and Regulatory Challenges of a Multiple Site Urban Remediation Project - 13119

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

Ferguson Jones, Andrea; Lee, Angela; Palmeter, Tim

2013-07-01

The Port Hope Project is part of the larger CAN$1.28 billion Port Hope Area Initiative (PHAI), a community-based program for the development and implementation of a safe, local, long-term management solution for historic Low-Level Radioactive Waste (LLRW) in the Municipalities of Port Hope and Clarington, Ontario, Canada. Atomic Energy of Canada (AECL) is the Project Proponent, Public Works and Government Services (PWGSC) is managing the procurement of services and the MMM Group Limited - Conestoga Rovers and Associates Joint Venture (MMM-CRA Joint Venture) is providing detailed design and construction oversight and administration services for the Project. The Port Hope Projectmore » includes the construction of a long-term waste management facility (LTWMF) in the Municipality of Port Hope and the remediation of 18 (eighteen) large-scale LLRW, numerous small-scale sites still being identified and industrial sites within the Municipality. The total volume to be remediated is over one million cubic metres and will come from sites that include temporary storage sites, ravines, beaches, parks, private commercial and residential properties and vacant industrial sites all within the urban area of Port Hope. Challenges that will need to be overcome during this 10 year project include: - Requirements stipulated by the Environmental Assessment (EA) that affect Project logistics and schedule. - Coordination of site remediation with the construction schedule at the LTWMF. - Physical constraints on transport routes and at sites affecting production rates. - Despite being an urban undertaking, seasonal constrains for birds and fish (i.e., nesting and spawning seasons). - Municipal considerations. - Site-specific constraints. - Site interdependencies exist requiring consideration in the schedule. Several sites require the use of an adjacent site for staging. (authors)« less

Recruitment of participants to a multiple sclerosis trial: The CombiRx experience

PubMed Central

Bhanushali, Minal J; Gustafson, Tarah; Powell, Steve; Conwit, Robin A; Wolinsky, Jerry S; Cutter, Gary R; Lublin, Fred; Cofield, Stacey S

2014-01-01

Background and Purpose: Participant recruitment is central to all clinical trials. Any delay in recruitment affects the completion and ultimate success of the trial. We report our experience with patient screening and randomization in CombiRx, which may inform the design of other trials. CombiRx was a multi-center, phase III, double-blind, randomized clinical trial comparing the combined use of interferon beta-1a and glatiramer acetate to either agent alone in patients with relapsing-remitting multiple sclerosis (RRMS). This trial was launched in January 2005 in 69 centers in the U.S. and Canada under a co-operative agreement with the National Institute of Neurological Disorders and Stroke (NINDS). The goal was to recruit 1000 patients over 1.5 years after a 6 month startup period. Instead, the investigators required 4.25 years to enroll 1008 patients. Methods: During this trial, we assessed the effectiveness of various recruitment strategies, utility of rescreening prior screen failures, and potential factors and strategies used in study conduct, research and infrastructure, all of which affected recruitment of participants and ultimately time to completion of CombiRx. We particularly were interested in the variability in time to site initiation between academic centers and private practice sites. Results: Physicians who were directly involved in the medical care of patients with RRMS were the primary source of patients recruited to CombiRx. A flexible study design that allowed for re-screening of the initial screen failures after a period of time was useful due to the relapsing/remitting course of the disease. Academic centers took longer to implement the trial than the private practice centers, but once sites were approved for enrollment, there was no important difference in the number of participants enrolled. Limitations: The CombiRx trial was conducted during a period when multiple new medications were being tested, thus affecting the pace of recruitment and limiting ability to generalize our experiences. However, the lessons we learned about process are relevant. Conclusion: Participants can be enrolled successfully in a clinical trial for RRMS, but factors affecting the time to achieve the requirements needed to start screening can be unpredictable and problematic. Prospective planning by the sponsors and investigators, use of central IRBs, master trial agreements and secure remote desktop access to the trial database may expedite trial implementation and participant recruitment. A good scientific research question with flexible study design and active involvement of the clinicians are important factors driving recruitment. Clinical trials can be implemented successfully both in private practices and at academic centers, a consideration when selecting sites. PMID:24686106

Observation of seasonal variation of atmospheric multiple-muon events in the MINOS Near and Far Detectors

DOE PAGES

Adamson, P.; Bishai, M.; Diwan, M. V.; ...

2015-06-09

We report the first observation of seasonal modulations in the rates of cosmic ray multiple-muon events at two underground sites, the MINOS Near Detector with an overburden of 225 mwe, and the MINOS Far Detector site at 2100 mwe. At the deeper site, multiple-muon events with muons separated by more than 8 m exhibit a seasonal rate that peaks during the summer, similar to that of single-muon events. Conversely, the rate of multiple-muon events with muons separated by less than 5–8 m, and the rate of multiple-muon events in the smaller, shallower Near Detector, exhibit a seasonal rate modulation thatmore » peaks in the winter.« less

Initation of pitting corrosion in martensitic stainless steels. [17-4PH; 13-8Mo; Custom 450

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

Cieslak, W.R.; Semarge, R.E.; Bovard, F.S.

1986-01-01

The form of localized corrosion known as pitting often initiates preferentially at microstructural inhomogeneities. The pit initiation resistance, therefore, is controlled by the characteristics of the initiation sites, rather than by the bulk material composition. This investigation correlates the pit initiation resistance, as measured by critical pitting potentials, with preferred pit initiation sites for 3 martensitic stainless steels. Pit initiation sites are determined by secondary electron (SE) and backscattered electron (BSE) imaging and energy dispersive and wavelength dispersive spectrometries (EDS and WDS) with a scalling electron microscope (SEM) and an electron probe microanalyzer (EPMA).

Multiple Site-Directed and Saturation Mutagenesis by the Patch Cloning Method.

PubMed

Taniguchi, Naohiro; Murakami, Hiroshi

2017-01-01

Constructing protein-coding genes with desired mutations is a basic step for protein engineering. Herein, we describe a multiple site-directed and saturation mutagenesis method, termed MUPAC. This method has been used to introduce multiple site-directed mutations in the green fluorescent protein gene and in the moloney murine leukemia virus reverse transcriptase gene. Moreover, this method was also successfully used to introduce randomized codons at five desired positions in the green fluorescent protein gene, and for simple DNA assembly for cloning.

Mission design for an orbiting volcano observatory

NASA Technical Reports Server (NTRS)

Penzo, Paul A.; Johnston, M. Daniel

1990-01-01

The Mission to Planet Earth initiative will require global observation of land, sea, and atmosphere, and all associated phenomena over the coming years; perhaps for decades. A major phenomenon playing a major part in earth's environment is volcanic activity. Orbital observations, including IR, UV, and visible imaging, may be made to monitor many active sites, and eventually increase our understanding of volcanoes and lead to the predictability of eruptions. This paper presents the orbital design and maneuvering capability of a low cost, volcano observing satellite, flying in low earth orbit. Major science requirements include observing as many as 10 to 20 active sites daily, or every two or three days. Given specific geographic locations of these sites, it is necessary to search the trajectory space for those orbits which maximize overflight opportunities. Also, once the satellite is in orbit, it may be desirable to alter the orbit to fly over targets of opportunity. These are active areas which are not being monitored, but which give indications of erupting, or have in fact erupted. Multiple impulse orbital maneuvering methods have been developed to minimize propellant usage for these orbital changes.

Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase.

PubMed

Liyasova, Mariya S; Schopfer, Lawrence M; Lockridge, Oksana

2013-03-25

Cresyl saligenin phosphate (CBDP) is a suspected causative agent of "aerotoxic syndrome", affecting pilots, crew members and passengers. CBDP is produced in vivo from ortho-containing isomers of tricresyl phosphate (TCP), a component of jet engine lubricants and hydraulic fluids. CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198). Inhibited BChE undergoes aging to release saligenin and o-cresol. The active site histidine (His-438) was hypothesized to abstract o-hydroxybenzyl moiety from the initial adduct on Ser-198. Our goal was to test this hypothesis. Mass spectral analysis of CBDP-inhibited BChE digested with Glu-C showed an o-hydroxybenzyl adduct (+106 amu) on lysine 499, a residue far from the active site, but not on His-438. Nevertheless, the nitrogen of the imidazole ring of free L-histidine formed a variety of adducts upon reaction with CBDP, including the o-hydroxybenzyl adduct, suggesting that histidine-CBDP adducts may form on other proteins. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase

PubMed Central

Liyasova, Mariya S.; Schopfer, Lawrence M.; Lockridge, Oksana

2012-01-01

Cresyl saligenin phosphate (CBDP) is a suspected causative agent of “aerotoxic syndrome”, affecting pilots, crew members and passengers. CBDP is produced in vivo from ortho-containing isomers of tricresyl phosphate (TCP), a component of jet engine lubricants and hydraulic fluids. CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198). Inhibited BChE undergoes aging to release saligenin and o-cresol. The active site histidine (His-438) was hypothesized to abstract o-hydroxybenzyl moiety from the initial adduct on Ser-198. Our goal was to test this hypothesis. Mass spectral analysis of CBDP-inhibited BChE digested with Glu-C showed an o-hydroxybenzyl adduct (+106 amu) on lysine 499, a residue far from the active site, but not on His-438. Nevertheless, the nitrogen of the imidazole ring of free L-histidine formed a variety of adducts upon reaction with CBDP, including the o-hydroxybenzyl adduct, suggesting that histidine-CBDP adducts may form on other proteins. PMID:22898212

Functional characterization of the 5'-flanking and the promoter region of the human UCP3 (hUCP3) gene.

PubMed

Tu, N; Chen, H; Winnikes, U; Reinert, I; Pirke, K M; Lentes, K U

2000-09-22

Uncoupling protein-3 (UCP3) is considered as an important regulator of energy expenditure and thermogenesis in humans. To get insight into the mechanisms regulating its expression we have cloned and characterized about 5 kb of the 5'-flanking region of the human UCP3 (hUCP3) gene. 5'-RACE analysis suggested a single transcription initiation site 187 bp upstream from the translational start site. The promoter region contains both TATA and CAAT boxes as well as consensus motifs for PPRE, TRE, CRE and muscle-specific factors like MyoD and MEF2 sites. Functional characterization of a 3 kb hUCP3 promoter fragment in multiple cell lines using a CAT-ELISA identified a cis-acting negative regulatory element between -2983 and -982 while the region between -982 and -284 showed greatly increased basal promoter activity suggesting the presence of a strong enhancer element. Promoter activity was particularly enhanced in the murine skeletal muscle cell line C2C12 reflecting the tissue-selective expression pattern of UCP3.

Nitrogen removal pathway of anaerobic ammonium oxidation in on-site aged refuse bioreactor.

PubMed

Wang, Chao; Zhao, Youcai; Xie, Bing; Peng, Qing; Hassan, Muhammad; Wang, Xiaoyuan

2014-05-01

The nitrogen removal pathways and nitrogen-related functional genes in on-site three-stage aged refuse bioreactor (ARB) treating landfill leachate were investigated. It was found that on average 90.0% of CODCr, 97.6% of BOD5, 99.3% of NH4(+)-N, and 81.0% of TN were removed with initial CODCr, BOD5, NH4(+)-N, and TN concentrations ranging from 2323 to 2754, 277 to 362, 1237 to 1506, and 1251 to 1580 mg/L, respectively. Meanwhile, the functional genes amoA, nirS and anammox 16S rRNA gene were found to coexist in every bioreactor, and their relative proportions in each bioreactor were closely related to the pollutant removal performance of the corresponding bioreactor, which indicated the coexistence of multiple nitrogen removal pathways in the ARB. Detection of anammox expression proved the presence of the anammox nitrogen removal pathway during the process of recirculating mature leachate to the on-site ARB, which provides important information for nitrogen management in landfills. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of the relationships between DCS cloud properties, lifecycle, and precipitation with meteorological regimes and aerosol sources at the ARM SGP Site

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

Dong, Xiquan

In this proposed research, we will investigate how different meteorological regimes and aerosol sources affect DCS properties, diurnal and life cycles, and precipitation using multiple observational platforms (surface, satellite, and aircraft) and NARR reanalysis at the ARM SGP site. The Feng et al. (2011, 2012) DCS results will serve as a starting point for this proposed research, and help us to address some fundamental issues of DCSs, such as convective initiation, rain rate, areal extent (including stratiform and convective regions), and longevity. Convective properties will be stratified by meteorological regime (synoptic/mesoscale patterns) identified by reanalysis. Aerosol information obtained from themore » ARM SGP site will also be stratified by meteorological regimes to understand their effects on convection. Finally, the aircraft in-situ measurements and various radar observations and retrievals during the MC3E campaign will provide a “cloud-truth” dataset and are an invaluable data source for verifying the findings and investigating the proposed hypotheses in Objective 1.« less

KGF and EGF signalling block hair follicle induction and promote interfollicular epidermal fate in developing mouse skin

PubMed Central

Richardson, Gavin D.; Bazzi, Hisham; Fantauzzo, Katherine A.; Waters, James M.; Crawford, Heather; Hynd, Phil; Christiano, Angela M.; Jahoda, Colin A. B.

2009-01-01

Summary A key initial event in hair follicle morphogenesis is the localised thickening of the skin epithelium to form a placode, partitioning future hair follicle epithelium from interfollicular epidermis. Although many developmental signalling pathways are implicated in follicle morphogenesis, the role of epidermal growth factor (EGF) and keratinocyte growth factor (KGF, also known as FGF7) receptors are not defined. EGF receptor (EGFR) ligands have previously been shown to inhibit developing hair follicles; however, the underlying mechanisms have not been characterised. Here we show that receptors for EGF and KGF undergo marked downregulation in hair follicle placodes from multiple body sites, whereas the expression of endogenous ligands persist throughout hair follicle initiation. Using embryonic skin organ culture, we show that when skin from the sites of primary pelage and whisker follicle development is exposed to increased levels of two ectopic EGFR ligands (HBEGF and amphiregulin) and the FGFR2(IIIb) receptor ligand KGF, follicle formation is inhibited in a time- and dose-dependent manner. We then used downstream molecular markers and microarray profiling to provide evidence that, in response to KGF and EGF signalling, epidermal differentiation is promoted at the expense of hair follicle fate. We propose that hair follicle initiation in placodes requires downregulation of the two pathways in question, both of which are crucial for the ongoing development of the interfollicular epidermis. We have also uncovered a previously unrecognised role for KGF signalling in the formation of hair follicles in the mouse. PMID:19474150

Multiple Comorbidities and Interest in Research Participation Among Clients of a Nonprofit Food Distribution Site.

PubMed

Higashi, Robin T; Craddock Lee, Simon J; Leonard, Tammy; Cuate, Erica L; Cole, Jay; Pruitt, Sandi L

2015-10-01

Persons accessing food from nonprofit distribution sites face numerous challenges and typically have significant unmet health needs. However, given limited and intermittent healthcare system engagement, this vulnerable population is underrepresented in clinical research. We sought to better understand the health needs of a nonclinical population to inform future research and interventions. Focus groups were conducted in English (n = 4) and Spanish (n = 4) with clients of Crossroads Community Services (CCS), the largest distributor of North Texas Food Bank. Discussions probed participants' health status, healthcare utilization, understanding and utilization of mammography, and attitudes toward participation in research. Participants included 42 CCS clients, primarily Hispanic or African American women. Participants reported multiple comorbid conditions among household members, yet utilization of health services was often limited by cost. The majority expressed interest in participating in research to communicate their health concerns and obtain emotional support. CCS clients represent a high-need, under-reached population willing to engage in health-related research that affords them opportunity to connect with peers in group settings and obtain information to improve management of daily life challenges. The Community Assistance Research (CARe) Initiative, a community-academic collaboration, establishes a much-needed opportunity for ongoing clinical research and intervention among this underserved population. © 2015 Wiley Periodicals, Inc.

Advantages of a Modular Mars Surface Habitat Approach

NASA Technical Reports Server (NTRS)

Rucker, Michelle A.; Hoffman, Stephan J.; Andrews, Alida; Watts, Kevin

2018-01-01

Early crewed Mars mission concepts developed by the National Aeronautics and Space Administration (NASA) assumed a single, large habitat would house six crew members for a 500-day Mars surface stay. At the end of the first mission, all surface equipment, including the habitat, -would be abandoned and the process would be repeated at a different Martian landing site. This work was documented in a series of NASA publications culminating with the Mars Design Reference Mission 5.0 (NASA-SP-2009-566). The Evolvable Mars Campaign (EMC) explored whether re-using surface equipment at a single landing site could be more affordable than the Apollo-style explore-abandon-repeat mission cadence. Initial EMC assumptions preserved the single, monolithic habitat, the only difference being a new requirement to reuse the surface habitat for multiple expedition crews. A trade study comparing a single large habitat versus smaller, modular habitats leaned towards the monolithic approach as more mass-efficient. More recent work has focused on the operational aspects of building up Mars surface infrastructure over multiple missions, and has identified compelling advantages of the modular approach that should be considered before making a final decision. This paper explores Mars surface mission operational concepts and integrated system analysis, and presents an argument for the modular habitat approach.

Multiple Comorbidities and Interest in Research Participation Among Clients of a Nonprofit Food Distribution Site

PubMed Central

Higashi, Robin T.; Craddock Lee, Simon J.; Leonard, Tammy; Cuate, Erica L.; Cole, Jay

2015-01-01

Abstract Background Persons accessing food from nonprofit distribution sites face numerous challenges and typically have significant unmet health needs. However, given limited and intermittent healthcare system engagement, this vulnerable population is underrepresented in clinical research. We sought to better understand the health needs of a nonclinical population to inform future research and interventions. Methods : Focus groups were conducted in English (n = 4) and Spanish (n = 4) with clients of Crossroads Community Services (CCS), the largest distributor of North Texas Food Bank. Discussions probed participants’ health status, healthcare utilization, understanding and utilization of mammography, and attitudes toward participation in research. Results Participants included 42 CCS clients, primarily Hispanic or African American women. Participants reported multiple comorbid conditions among household members, yet utilization of health services was often limited by cost. The majority expressed interest in participating in research to communicate their health concerns and obtain emotional support. Conclusion CCS clients represent a high‐need, under‐reached population willing to engage in health‐related research that affords them opportunity to connect with peers in group settings and obtain information to improve management of daily life challenges. The Community Assistance Research (CARe) Initiative, a community–academic collaboration, establishes a much‐needed opportunity for ongoing clinical research and intervention among this underserved population. PMID:26277918

Lessons Learned Implementing DOORS in a Citrix Environment

NASA Technical Reports Server (NTRS)

Bussman, Marie

2005-01-01

NASA's James Web Space Telescope (JWST) Project is a large multi-national project with geographically dispersed contractors that all need access to the Projects requirement database. Initially, the project utilized multiple DOORS databases with the built-in partitions feature to exchange modules amongst the various contractor sites. As the requirements databases matured the use of partitions became extremely difficult. There have been many issues such as incompatible versions of DOORS, inefficient mechanism for sharing modules, security concerns, performance issues, and inconsistent document import and export formats. Deployment of the client software with limited IT resources available was also an issue. The solution chosen by JWST was to integrate the use of a Citrix environment with the DOORS database to address most of the project concerns. The use of the Citrix solution allowed a single Requirements database in a secure environment via a web interface. The Citrix environment allows JWST to upgrade to the most current version of DOORS without having to coordinate multiple sites and user upgrades. The single requirements database eliminates a multitude of Configuration Management concerns and facilitated the standardization of documentation formats. This paper discusses the obstacles and the lessons learned throughout the installation, implementation, usage and deployment process of a centralized DOORS database solution.

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

Adamson, P.; Bishai, M.; Diwan, M. V.

We report the first observation of seasonal modulations in the rates of cosmic ray multiple-muon events at two underground sites, the MINOS Near Detector with an overburden of 225 mwe, and the MINOS Far Detector site at 2100 mwe. At the deeper site, multiple-muon events with muons separated by more than 8 m exhibit a seasonal rate that peaks during the summer, similar to that of single-muon events. Conversely, the rate of multiple-muon events with muons separated by less than 5–8 m, and the rate of multiple-muon events in the smaller, shallower Near Detector, exhibit a seasonal rate modulation thatmore » peaks in the winter.« less

Uncovering a Salt Giant. Deep-Sea Record of Mediterranean Messinian Events (DREAM) multi-phase drilling project

NASA Astrophysics Data System (ADS)

Camerlenghi, Angelo; Aoisi, Vanni; Lofi, Johanna; Hübscher, Christian; deLange, Gert; Flecker, Rachel; Garcia-Castellanos, Daniel; Gorini, Christian; Gvirtzman, Zohar; Krijgsman, Wout; Lugli, Stefano; Makowsky, Yizhaq; Manzi, Vinicio; McGenity, Terry; Panieri, Giuliana; Rabineau, Marina; Roveri, Marco; Sierro, Francisco Javier; Waldmann, Nicolas

2014-05-01

In May 2013, the DREAM MagellanPlus Workshop was held in Brisighella (Italy). The initiative builds from recent activities by various research groups to identify potential sites to perform deep-sea scientific drilling in the Mediterranean Sea across the deep Messinian Salinity Crisis (MSC) sedimentary record. In this workshop three generations of scientists were gathered: those who participated in formulation of the deep desiccated model, through DSDP Leg 13 drilling in 1973; those who are actively involved in present-day MSC research; and the next generation (PhD students and young post-docs). The purpose of the workshop was to identify locations for multiple-site drilling (including riser-drilling) in the Mediterranean Sea that would contribute to solve the several open questions still existing about the causes, processes, timing and consequences at local and planetary scale of an outstanding case of natural environmental change in the recent Earth history: the Messinian Salinity Crisis in the Mediterranean Sea. The product of the workshop is the identification of the structure of an experimental design of site characterization, riser-less and riser drilling, sampling, measurements, and down-hole analyses that will be the core for at least one compelling and feasible multiple phase drilling proposal. Particular focus has been given to reviewing seismic site survey data available from different research groups at pan-Mediterranean basin scale, to the assessment of additional site survey activity including 3D seismics, and to ways of establishing firm links with oil and gas industry. The scientific community behind the DREAM initiative is willing to proceed with the submission to IODP of a Multi-phase Drilling Project including several drilling proposals addressing specific drilling objectives, all linked to the driving objectives of the MSC drilling and understanding . A series of critical drilling targets were identified to address the still open questions related to the MSC event. Several proposal ideas also emerged to support the Multi-phase drilling project concept: Salt tectonics and fluids, Deep stratigraphic and crustal drilling in the Gulf of Lion (deriving from the GOLD drilling project), Deep stratigraphic and crustal drilling in the Ionian Sea, Deep Biosphere, Sapropels, and the Red Sea. A second MagellanPlus workshop held in January 2014 in Paris (France), has proceeded a step further towards the drafting of the Multi-phase Drilling Project and a set of pre-proposals for submission to IODP.

Blocks in the asymmetric simple exclusion process

NASA Astrophysics Data System (ADS)

Tracy, Craig A.; Widom, Harold

2017-12-01

In earlier work, the authors obtained formulas for the probability in the asymmetric simple exclusion process that the mth particle from the left is at site x at time t. They were expressed in general as sums of multiple integrals and, for the case of step initial condition, as an integral involving a Fredholm determinant. In the present work, these results are generalized to the case where the mth particle is the left-most one in a contiguous block of L particles. The earlier work depended in a crucial way on two combinatorial identities, and the present work begins with a generalization of these identities to general L.

Inductive Double-Contingency Analysis of UO2 Powder Bulk Blending Operations at a Commercial Fuel Plant (U)

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

Skiles, S. K.

1994-12-22

An inductive double-contingency analysis (DCA) method developed by the criticality safety function at the Savannah River Site, was applied in Criticality Safety Evaluations (CSEs) of five major plant process systems at the Westinghouse Electric Corporation`s Commercial Nuclear Fuel Manufacturing Plant in Columbia, South Carolina (WEC-Cola.). The method emphasizes a thorough evaluation of the controls intended to provide barriers against criticality for postulated initiating events, and has been demonstrated effective at identifying common mode failure potential and interdependence among multiple controls. A description of the method and an example of its application is provided.

Groundwater data for selected wells within the Eastern San Joaquin Groundwater Subbasin, California, 2003-8

USGS Publications Warehouse

Clark, Dennis A.; Izbicki, John A.; Metzger, Loren F.; Everett, Rhett; Smith, Gregory A.; O'Leary, David R.; Teague, Nicholas F.; Burgess, Matthew K.

2012-01-01

Data were collected by the U.S. Geological Survey from 2003 through 2008 in the Eastern San Joaquin Groundwater Subbasin, 80 miles east of San Francisco, California, as part of a study of the increasing chloride concentrations in groundwater processes. Data collected include geologic, geophysical, chemical, and hydrologic data collected during and after the installation of five multiple-well monitoring sites, from three existing multiple-well sites, and from 79 selected public-supply, irrigation, and domestic wells. Each multiple-well monitoring site installed as part of this study contained three to five 2-inch diameter polyvinyl chloride (PVC)-cased wells ranging in depth from 68 to 880 feet below land surface. Continuous water-level data were collected from the 19 wells installed at these 5 sites and from 10 existing monitoring wells at 3 additional multiple-well sites in the study area. Thirty-one electromagnetic logs were collected seasonally from the deepest PVC-cased monitoring well at seven multiple-well sites. About 200 water samples were collected from 79 wells in the study area. Coupled well-bore flow data and depth-dependent water-quality data were collected from 12 production wells under pumped conditions, and well-bore flow data were collected from 10 additional wells under unpumped conditions.

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2013-01-01

The increasing availability of data from multi-site randomized trials provides a potential opportunity to use instrumental variables methods to study the effects of multiple hypothesized mediators of the effect of a treatment. We derive nine assumptions needed to identify the effects of multiple mediators when using site-by-treatment interactions…

Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations

PubMed Central

Streubel, Jana; Baum, Heidi; Grau, Jan; Stuttman, Johannes; Boch, Jens

2017-01-01

Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators. PMID:28301511

Dissection of TALE-dependent gene activation reveals that they induce transcription cooperatively and in both orientations.

PubMed

Streubel, Jana; Baum, Heidi; Grau, Jan; Stuttman, Johannes; Boch, Jens

2017-01-01

Plant-pathogenic Xanthomonas bacteria inject transcription activator-like effector proteins (TALEs) into host cells to specifically induce transcription of plant genes and enhance susceptibility. Although the DNA-binding mode is well-understood it is still ambiguous how TALEs initiate transcription and whether additional promoter elements are needed to support this. To systematically dissect prerequisites for transcriptional initiation the activity of one TALE was compared on different synthetic Bs4 promoter fragments. In addition, a large collection of artificial TALEs spanning the OsSWEET14 promoter was compared. We show that the presence of a TALE alone is not sufficient to initiate transcription suggesting the requirement of additional supporting promoter elements. At the OsSWEET14 promoter TALEs can initiate transcription from various positions, in a synergistic manner of multiple TALEs binding in parallel to the promoter, and even by binding in reverse orientation. TALEs are known to shift the transcriptional start site, but our data show that this shift depends on the individual position of a TALE within a promoter context. Our results implicate that TALEs function like classical enhancer-binding proteins and initiate transcription in both orientations which has consequences for in planta target gene prediction and design of artificial activators.

Biochemical Control of Fungal Biomass and Enzyme Production During Native Hawaiian Litter Degradation

NASA Astrophysics Data System (ADS)

Amatangelo, K. L.; Cordova, T. P.; Vitousek, P. M.

2007-12-01

Microbial growth and enzyme production during decomposition is controlled by the availability of carbon substrates, essential elements, and the ratios of these (such as lignin:N). We manipulated carbon:nutrient stoichiometry during decomposition using a natural fertility gradient in Hawaii and litter of varying initial biochemistry. We collected freshly senesced litter of seven biochemically distinct species from three sites offering differing levels of N, P, cations, and 15N , but similar yearly rainfall and temperature patterns. Litter types were decomposed at both the sites they were collected, and at the other site(s) that species was found. Litter was collected at multiple time points, and after one year of decomposition, calculated K constants varied an order of magnitude, from 0.276 to 2.76. Decomposition rates varied significantly with both litter site of origin and deployment, except at the oldest, P-limited site, where litter site of origin was not significantly correlated with decomposition within species. As microbial exocellular enzymes provide the catalyst for the breakdown of organic molecules including phenols, cellulose, and cutin, we assayed polyphenol oxidase, cellobiohydrolase, cutinase, chitinase, and lignin peroxidase to evaluate the breakdown sequence of different litter types. To measure the fungal biomass accumulating during decomposition, we extracted (22E)-Ergosta-5,7,22-trien-3beta- ol (ergosterol) on a subset of samples. The production of particular exocellular enzymes on litter species responded distinctly to origin and decomposition sites: after six months, chitinase and cellobiohydrolase were significantly affected by origin site, whereas polyphenol oxidase activity was controlled by deployment site. We conclude that site characteristics can alter the interaction between litter carbon:nutrient ratios and decomposition rate, mediated through microbial biomass and enzyme production.

Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

PubMed Central

van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

2014-01-01

Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

Identifying Martian Hydrothermal Sites: Geological Investigation Utilizing Multiple Datasets

NASA Technical Reports Server (NTRS)

Dohm, J. M.; Baker, V. R.; Anderson, R. C.; Scott, D. H.; Rice, J. W., Jr.; Hare, T. M.

2000-01-01

Comprehensive geological investigations of martian landscapes that may have been modified by magmatic-driven hydrothermal activity, utilizing multiple datasets, will yield prime target sites for future hydrological, mineralogical, and biological investigations.

Initiation and growth of multiple-site damage in the riveted lap joint of a curved stiffened fuselage panel: An experimental and analytical study

NASA Astrophysics Data System (ADS)

Ahmed, Abubaker Ali

As part of the structural integrity research of the National Aging Aircraft Research Program, a comprehensive study on multiple-site damage (MSD) initiation and growth in a pristine lap-joint fuselage panel has been conducted. The curved stiffened fuselage panel was tested at the Full-Scale Aircraft Structural Test Evaluation and Research (FASTER) facility located at the Federal Aviation Administration William J. Hughes Technical Center. A strain survey test was conducted to verify proper load application. The panel was then subjected to a fatigue test with constant-amplitude cyclic loading. The applied loading spectrum included underload marker cycles so that crack growth history could be reconstructed from post-test fractographic examinations. Crack formation and growth were monitored via nondestructive and high-magnification visual inspections. Strain gage measurements recorded during the strain survey tests indicated that the inner surface of the skin along the upper rivet row of the lap joint experienced high tensile stresses due to local bending. During the fatigue loading, cracks were detected by eddy-current inspections at multiple rivet holes along the upper rivet row. Through-thickness cracks were detected visually after about 80% of the fatigue life. Once MSD cracks from two adjacent rivet holes linked up, there was a quick deterioration in the structural integrity of the lap joint. The linkup resulted in a 2.87" (72.9-mm) lead fatigue crack that rapidly propagated across 12 rivet holes and crossed over into the next skin bay, at which stage the fatigue test was terminated. A post-fatigue residual strength test was then conducted by loading the panel quasi-statically up to final failure. The panel failed catastrophically when the crack extended instantaneously across three additional bays. Post-test fractographic examinations of the fracture surfaces in the lap joint of the fuselage panel were conducted to characterize subsurface crack initiation and growth. Results showed evidence of fretting damage and crack initiation at multiple locations near the rivet holes along the faying surface of the skin. The subsurface cracks grew significantly along the faying surface before reaching the outer surface of the skin, forming elliptical crack fronts. A finite element model (FE) of the panel was constructed and geometrically-nonlinear analyses conducted to determine strain distribution under the applied loads. The FE model was validated by comparing the analysis results with the strain gage measurements recorded during the strain survey test. The validated FE model was then used to determine stress-intensity factors at the crack tips. Stress-intensity factor results indicated that crack growth in the lap joint was under mixed-mode; however, the opening-mode stress intensity factor was dominant. The stress-intensity factors computed from the FE analysis were used to conduct cycle-by-cycle integration of fatigue crack growth. In the cycle-by-cycle integration, the NASGRO crack growth model was used with its parameters selected to account for the effects of plasticity-induced crack closure and the test environment on crack growth rate. Fatigue crack growth predictions from cycle-by-cycle computation were in good agreement with the experimental measured crack growth data. The results of the study provide key insights into the natural development and growth of MSD cracks in the pristine lap joint. The data provided by the study represent a valuable source for the evaluation and validation of analytical methodologies used for predicting MSD crack initiation and growth.

The value of testing multiple anatomic sites for gonorrhoea and chlamydia in sexually transmitted infection centres in the Netherlands, 2006-2010.

PubMed

Koedijk, F D H; van Bergen, J E A M; Dukers-Muijrers, N H T M; van Leeuwen, A P; Hoebe, C J P A; van der Sande, M A B

2012-09-01

National surveillance data from 2006 to 2010 of the Dutch sexually transmitted infection (STI) centres were used to analyse current practices on testing extragenital sites for chlamydia and gonorrhoea in men who have sex with men (MSM) and women. In MSM, 76.0% and 88.9% were tested at least at one extragenital site (pharyngeal and/or anorectal) for chlamydia and gonorrhoea, respectively; for women this was 20.5% and 30.2%. Testing more than one anatomic site differed by STI centre, ranging from 2% to 100%. In MSM tested at multiple sites, 63.0% and 66.5% of chlamydia and gonorrhoea diagnoses, respectively, would have been missed if screened at the urogenital site only, mainly anorectal infections. For women tested at multiple sites, the proportions of missed chlamydia and gonorrhoea diagnoses would have been 12.9% and 30.0%, respectively. Testing extragenital sites appears warranted, due to the numerous infections that would have been missed. Adding anorectal screening to urogenital screening for all MSM visiting an STI centre should be recommended. Since actual testing practices differ by centre, there is a need for clearer guidelines. Routine gonorrhoea and chlamydia screening at multiple sites in STI centres should be investigated further as this might be a more effective approach to reduce transmission than current practice.

Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use.

PubMed

Bagaglio, Sabrina; Uberti-Foppa, Caterina; Morsica, Giulia

2017-07-01

Multiple direct-acting antiviral (DAA)-based regimens are currently approved that provide one or more interferon-free treatment options for hepatitis C virus (HCV) genotypes (G) 1-6. The choice of a DAA regimen, duration of therapy, and use of ribavirin depends on multiple viral and host factors, including HCV genotype, the detection of resistance-associated amino acid (aa) substitutions (RASs), prior treatment experience, and presence of cirrhosis. In regard to viral factors that may guide the treatment choice, the most important is the infecting genotype because a number of DAAs are genotype-designed. The potency and the genetic barrier may also impact the choice of treatment. One important and debated possible virologic factor that may negatively influence the response to DAAs is the presence of baseline RASs. Baseline resistance testing is currently not routinely considered or recommended for initiating HCV treatment, due to the overall high response rates (sustained virological response >90%) obtained. Exceptions are patients infected by HCV G1a when initiating treatment with simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in sites of resistance. On the basis of these observations, first-line strategies should be optimized to overcome treatment failure due to HCV resistance.

The positive regulatory function of the 5'-proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences.

PubMed Central

Williams, N P; Mueller, P P; Hinnebusch, A G

1988-01-01

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function. Images PMID:3065626

Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting.

PubMed

Gibney, Geoffrey T; Gauthier, Geneviève; Ayas, Charles; Galebach, Philip; Wu, Eric Q; Abhyankar, Sarang; Reyes, Carolina; Guérin, Annie; Yim, Yeun Mi

2015-08-01

Brain metastases are a common and serious complication among patients with metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated clinical efficacy in patients with BRAF V600E-mutant melanoma brain metastases (MBM). We examined the real-world application and clinical outcomes of vemurafenib in this patient population. Demographic, treatment patterns, response, and survival data were collected from medical charts. Clinical data on 283 patients with active BRAF V600E-mutant MBM treated with vemurafenib were provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5% had ECOG performance status of 0-1, and 43.1% used corticosteroids at vemurafenib initiation. Median follow-up was 5.7 months. Following vemurafenib initiation, 48.1% of patients experienced intracranial response and 45.6% experienced extracranial response. The Kaplan-Meier estimate for overall survival was 59% at 12 months. Multivariate analyses showed associations between intracranial response and both corticosteroid use and vemurafenib as initial therapy after MBM diagnosis. Larger size (5-10 mm vs. < 5 mm) and number of brain metastases (≥ 5 vs. < 2) and progressive extracranial disease at treatment initiation were associated with decreased intracranial response and increased risk of disease progression. Multiple extracranial sites (2 vs. < 2) and the absence of local treatments were also associated with increased risk of progression. Increased risk of death was associated with ≥ 2 extracranial disease sites, progressive extracranial disease, and ≥ 5 brain metastases. Subgroups of MBM patients may derive more benefit with vemurafenib, warranting prospective investigation. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Laparoendoscopic single site (LESS) cholecystectomy.

PubMed

Hodgett, Steven E; Hernandez, Jonathan M; Morton, Connor A; Ross, Sharona B; Albrink, Michael; Rosemurgy, Alexander S

2009-02-01

The journey from conventional "open" operations to truly "minimally invasive" operations naturally includes progression from operations involving multiple trocars and multiple incisions to operations involving access through the umbilicus alone. Laparoscopic operations through the umbilicus alone, laparoendoscopic single site surgery (LESS), offer improved cosmesis and hopes for less pain and improved recovery. This study was undertaken to evaluate our initial experience with LESS cholecystectomy and to compare our initial experience to concurrent outcomes with more conventional multiport, multi-incision laparoscopic cholecystectomy. All patients referred for cholecystectomy over a 6-month period were offered LESS. Outcomes, including blood loss, operative time, complications, and length of stay were recorded. Outcomes with our first LESS cholecystectomies were compared to an uncontrolled group of concurrent patients undergoing multiport, multi-incision laparoscopic cholecystectomy at the same hospital by the same surgeon. Twenty-nine patients of median age 50 years undergoing LESS cholecystectomy from November 2007 until May 2008 were compared to 29* patients, median age 48 years, undergoing standard multiport, multiple-incision laparoscopic cholecystectomy over the same time period. Median operative time for patients undergoing LESS cholecystectomy was 72 min and was not different from that of patients undergoing multiport, multi-incision laparoscopic cholecystectomy (p = 0.81). Median length of hospital stay was 1.0 day for patients undergoing LESS cholecystectomy and was not different from patients undergoing standard laparoscopic cholecystectomy (p = 0.46). Operative estimated blood loss was less than 100 cc for all patients. No patients undergoing attempted LESS cholecystectomy had conversions to "open" operations; two patients had an additional trocar(s) placed distant from the umbilicus to aid in exposure. Three patients undergoing LESS cholecystectomy had complications: two were troubled by pain control and another had urinary retention. LESS cholecystectomy is a safe and effective alternative to standard laparoscopic cholecystectomy. It can be undertaken without the expense of added operative time and provides patients with minimal, if any, apparent scarring. We believe LESS cholecystectomy will be driven by consumer demand, and therefore, laparoscopic surgeons will need to become proficient with LESS procedures.

High-speed rupture during the initiation of the 2015 Bonin Islands deep earthquake

NASA Astrophysics Data System (ADS)

Zhan, Z.; Ye, L.; Shearer, P. M.; Lay, T.; Kanamori, H.

2015-12-01

Among the long-standing questions on how deep earthquakes rupture, the nucleation phase of large deep events is one of the most puzzling parts. Resolving the rupture properties of the initiation phase is difficult to achieve with far-field data because of the need for accurate corrections for structural effects on the waveforms (e.g., attenuation, scattering, and site effects) and alignment errors. Here, taking the 2015 Mw 7.9 Bonin Islands earthquake (depth = 678 km) as an example, we jointly invert its far-field P waves at multiple stations for the average rupture speed during the first second of the event. We use waveforms from a closely located aftershock as empirical Green's functions, and correct for possible differences in focal mechanisms and waveform misalignments with an iterative approach. We find that the average initial rupture speed is over 5 km/s, significantly higher than the average rupture speed of 3 km/s later in the event. This contrast suggests that rupture speeds of deep earthquakes can be highly variable during individual events and may define different stages of rupture, potentially with different mechanisms.

Pet Ownership and Cancer Risk in the Women's Health Initiative.

PubMed

Garcia, David O; Lander, Eric M; Wertheim, Betsy C; Manson, JoAnn E; Volpe, Stella L; Chlebowski, Rowan T; Stefanick, Marcia L; Lessin, Lawrence S; Kuller, Lewis H; Thomson, Cynthia A

2016-09-01

Pet ownership and cancer are both highly prevalent in the United States. Evidence suggests that associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. This was a prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women's Health Initiative observational study and clinical trials. Cox proportional hazards models were used to estimate HR and 95% confidence intervals for the association between pet ownership and cancer, adjusted for potential confounders. There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Pet ownership had no association with overall cancer incidence. This is the first large epidemiologic study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. Cancer Epidemiol Biomarkers Prev; 25(9); 1311-6. ©2016 AACR. ©2016 American Association for Cancer Research.

A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β

PubMed Central

Arima, Masaru; Iwata, Youhei; Morita, Yusuke; Kobayashi, Tsukane; Sasaki, Ryousuke; Suzuki, Kayoko; Matsunaga, Kayoko

2014-01-01

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion. PMID:24707255

Homologous Chromosome Pairing in Drosophila melanogaster Proceeds through Multiple Independent Initiations

PubMed Central

Fung, Jennifer C.; Marshall, Wallace F.; Dernburg, Abby; Agard, David A.; Sedat, John W.

1998-01-01

The dynamics by which homologous chromosomes pair is currently unknown. Here, we use fluorescence in situ hybridization in combination with three-dimensional optical microscopy to show that homologous pairing of the somatic chromosome arm 2L in Drosophila occurs by independent initiation of pairing at discrete loci rather than by a processive zippering of sites along the length of chromosome. By evaluating the pairing frequencies of 11 loci on chromosome arm 2L over several timepoints during Drosophila embryonic development, we show that all 11 loci are paired very early in Drosophila development, within 13 h after egg deposition. To elucidate whether such pairing occurs by directed or undirected motion, we analyzed the pairing kinetics of histone loci during nuclear cycle 14. By measuring changes of nuclear length and correlating these changes with progression of time during cycle 14, we were able to express the pairing frequency and distance between homologous loci as a function of time. Comparing the experimentally determined dynamics of pairing to simulations based on previously proposed models of pairing motion, we show that the observed pairing kinetics are most consistent with a constrained random walk model and not consistent with a directed motion model. Thus, we conclude that simple random contacts through diffusion could suffice to allow pairing of homologous sites. PMID:9531544

Homologous chromosome pairing in Drosophila melanogaster proceeds through multiple independent initiations.

PubMed

Fung, J C; Marshall, W F; Dernburg, A; Agard, D A; Sedat, J W

1998-04-06

The dynamics by which homologous chromosomes pair is currently unknown. Here, we use fluorescence in situ hybridization in combination with three-dimensional optical microscopy to show that homologous pairing of the somatic chromosome arm 2L in Drosophila occurs by independent initiation of pairing at discrete loci rather than by a processive zippering of sites along the length of chromosome. By evaluating the pairing frequencies of 11 loci on chromosome arm 2L over several timepoints during Drosophila embryonic development, we show that all 11 loci are paired very early in Drosophila development, within 13 h after egg deposition. To elucidate whether such pairing occurs by directed or undirected motion, we analyzed the pairing kinetics of histone loci during nuclear cycle 14. By measuring changes of nuclear length and correlating these changes with progression of time during cycle 14, we were able to express the pairing frequency and distance between homologous loci as a function of time. Comparing the experimentally determined dynamics of pairing to simulations based on previously proposed models of pairing motion, we show that the observed pairing kinetics are most consistent with a constrained random walk model and not consistent with a directed motion model. Thus, we conclude that simple random contacts through diffusion could suffice to allow pairing of homologous sites.

Pet Ownership and Cancer Risk in the Women’s Health Initiative

PubMed Central

Garcia, David O.; Lander, Eric M.; Wertheim, Betsy C.; Manson, JoAnn E.; Volpe, Stella L.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Lessin, Lawrence S.; Kuller, Lewis H.; Thomson, Cynthia A.

2016-01-01

Background Pet ownership and cancer are both highly prevalent in the U.S. Evidence suggest associations may exist between this potentially modifiable factor and cancer prevention, though studies are sparse. The present report examined whether pet ownership (dog, cat, or bird) is associated with lower risk for total cancer and site-specific obesity-related cancers. Methods A prospective analysis of 123,560 participants (20,981 dog owners; 19,288 cat owners; 1,338 bird owners; and 81,953 non-pet owners) enrolled in the Women’s Health Initiative (WHI) observational study and clinical trials. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between pet ownership and cancer, adjusted for potential confounders. Results There were no significant relationships between ownership of a dog, cat, or bird and incidence of cancer overall. When site-specific cancers were examined, no associations were observed after adjustment for multiple comparisons. Conclusion Pet ownership had no association with overall cancer incidence. Impact This is the first large epidemiological study to date to explore relationships between pet ownership and cancer risk, as well as associated risks for individual cancer types. This study requires replication in other sizable, diverse cohorts. PMID:27365150

A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β.

PubMed

Arima, Masaru; Iwata, Youhei; Morita, Yusuke; Kobayashi, Tsukane; Sasaki, Ryousuke; Suzuki, Kayoko; Matsunaga, Kayoko

2014-01-01

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion.

Application of multiple tracers (SF6 and chloride) to identify the transport by characteristics of contaminant at two separate contaminated sites

NASA Astrophysics Data System (ADS)

Lee, K. K.; Lee, S. S.; Kim, H. H.; Koh, E. H.; Kim, M. O.; Lee, K.; Kim, H. J.

2016-12-01

Multiple tracers were applied for source and pathway detection at two different sites. CO2 gas injected in the subsurface for a shallow-depth CO2 injection and leak test can be regarded as a potential contaminant source. Therefore, it is necessary to identify the migration pattern of CO2 gas. Also, at a DNAPL contaminated site, it is important to figure out the characteristics of plume evolution from the source zone. In this study, multiple tracers (SF6 and chloride) were used to evaluate the applicability of volatile and non-volatile tracers and to identify the characteristics of contaminant transport at each CO2 injection and leak test site and DNAPL contaminated site. Firstly, at the CO2 test site, multiple tracers were used to perform the single well push-drift-pull tracer test at total 3 specific depth zones. As results of tests, volatile and non-volatile tracers showed different mass recovery percentage. Most of chloride mass was recovered but less than half of SF6 mass was recovered due to volatile property. This means that only gaseous SF6 leak out to unsaturated zone. However, breakthrough curves of both tracers indicated similar peak time, effective porosity, and regional groundwater velocity. Also, at both contaminated sites, natural gradient tracer tests were performed with multiple tracers. With the results of natural gradient tracer test, it was possible to confirm the applicability of multiple tracers and to understand the contaminant transport in highly heterogeneous aquifer systems through the long-term monitoring of tracers. Acknowledgement: financial support was provided by the R&D Project on Environmental Management of Geologic CO2 Storage)" from the KEITI (Project Number: 2014001810003) and Korea Ministry of Environment as "The GAIA project (2014000540010)".

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

Adamson, P.

We report the first observation of seasonal modulations in the rates of cosmic ray multiple-muon events at two underground sites, the MINOS Near Detector with an overburden of 225 mwe, and the MINOS Far Detector site at 2100 mwe. Thus, at the deeper site, multiple-muon events with muons separated by more than 8 m exhibit a seasonal rate that peaks during the summer, similar to that of single-muon events. In contrast and unexpectedly, the rate of multiple-muon events with muons separated by less than 5–8 m, and the rate of multiple-muon events in the smaller, shallower Near Detector, exhibit amore » seasonal rate modulation that peaks in the winter.« less

Traditions in Spider Monkeys Are Biased towards the Social Domain

PubMed Central

Santorelli, Claire J.; Schaffner, Colleen M.; Campbell, Christina J.; Notman, Hugh; Pavelka, Mary S.; Weghorst, Jennifer A.; Aureli, Filippo

2011-01-01

Cross-site comparison studies of behavioral variation can provide evidence for traditions in wild species once ecological and genetic factors are excluded as causes for cross-site differences. These studies ensure behavior variants are considered within the context of a species' ecology and evolutionary adaptations. We examined wide-scale geographic variation in the behavior of spider monkeys (Ateles geoffroyi) across five long-term field sites in Central America using a well established ethnographic cross-site survey method. Spider monkeys possess a relatively rare social system with a high degree of fission-fusion dynamics, also typical of chimpanzees (Pan troglodytes) and humans (Homo sapiens). From the initial 62 behaviors surveyed 65% failed to meet the necessary criteria for traditions. The remaining 22 behaviors showed cross-site variation in occurrence ranging from absent through to customary, representing to our knowledge, the first documented cases of traditions in this taxon and only the second case of multiple traditions in a New World monkey species. Of the 22 behavioral variants recorded across all sites, on average 57% occurred in the social domain, 19% in food-related domains and 24% in other domains. This social bias contrasts with the food-related bias reported in great ape cross-site comparison studies and has implications for the evolution of human culture. No pattern of geographical radiation was found in relation to distance across sites. Our findings promote A. geoffroyi as a model species to investigate traditions with field and captive based experiments and emphasize the importance of the social domain for the study of animal traditions. PMID:21373196

ESTABLISHING A NATURE CONSERVANCY GULF OF MEXICO INITIATIVE MX974946

EPA Science Inventory

The Conservancy will initiate a three-year pilot program to create a Gulf of Mexico Initiative within TNC to coordinate and enhance site-based conservation work at priority Gulf coastal sites. TNC would hire an ecologist to serve as the director of TNC's Gulf of Mexico Initiative...

Tectonic evolution of the outer Izu-Bonin-Mariana fore arc system: initial results from IODP Expedition 352

NASA Astrophysics Data System (ADS)

Kurz, W.; Ferre, E. C.; Robertson, A. H. F.; Avery, A. J.; Kutterolf, S.

2015-12-01

During International Ocean Discovery Program (IODP) Expedition 352, a section through the volcanic stratigraphy of the outer fore arc of the Izu-Bonin-Mariana (IBM) system was drilled to trace magmatism, tectonics, and crustal accretion associated with subduction initiation. Structures within drill cores, borehole and site survey seismic data indicate that tectonic deformation in the outer IBM fore arc is mainly post-magmatic. Extension generated asymmetric sediment basins such as half-grabens at sites 352-U1439 and 352-U1442 on the upper trench slope. Along their eastern margins the basins are bounded by west-dipping normal faults. Deformation was localized along multiple sets of faults, accompanied by syn-tectonic pelagic and volcaniclastic sedimentation. The lowermost sedimentary units were tilted eastward by ~20°. Tilted beds were covered by sub-horizontal beds. Biostratigraphic constraints reveal a minimum age of the oldest sediments at ~ 35 Ma; timing of the sedimentary unconformities is between ~ 27 and 32 Ma. At sites 352-U1440 and 352-U1441 on the outer fore arc strike-slip faults are bounding sediment basins. Sediments were not significantly affected by tectonic tilting. Biostratigraphy gives a minimum age of the basement-cover contact between ~29.5 and 32 Ma. The post-magmatic structures reveal a multiphase tectonic evolution of the outer IBM fore arc. At sites 352-U1439 and 352-U1442, shear with dominant reverse to oblique reverse displacement was localized along subhorizontal fault zones, steep slickensides and shear fractures. These were either re-activated as or cut by normal-faults and strike-slip faults. Extension was also accommodated by steep to subvertical mineralized veins and extensional fractures. Faults at sites 352-U1440 and 352-U1441 show mainly strike-slip kinematics. Sediments overlying the igneous basement(maximum Late Eocene to Recent age), document ash and aeolian input, together with mass wasting of the fault-bounded sediment ponds.

Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

PubMed Central

Marseille, Elliot; Giganti, Mark J.; Mwango, Albert; Chisembele-Taylor, Angela; Mulenga, Lloyd; Over, Mead; Kahn, James G.; Stringer, Jeffrey S. A.

2012-01-01

Background We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ). Methods We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years. Results The program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector. Conclusions and Significance The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts. PMID:23284843

Taking ART to scale: determinants of the cost and cost-effectiveness of antiretroviral therapy in 45 clinical sites in Zambia.

PubMed

Marseille, Elliot; Giganti, Mark J; Mwango, Albert; Chisembele-Taylor, Angela; Mulenga, Lloyd; Over, Mead; Kahn, James G; Stringer, Jeffrey S A

2012-01-01

We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ). We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years. The program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector. The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.

Diagnosis and Treatment of Bone Disease in Multiple Myeloma: Spotlight on Spinal Involvement

PubMed Central

Tosi, Patrizia

2013-01-01

Bone disease is observed in almost 80% of newly diagnosed symptomatic multiple myeloma patients, and spine is the bone site that is more frequently affected by myeloma-induced osteoporosis, osteolyses, or compression fractures. In almost 20% of the cases, spinal cord compression may occur; diagnosis and treatment must be carried out rapidly in order to avoid a permanent sensitive or motor defect. Although whole body skeletal X-ray is considered mandatory for multiple myeloma staging, magnetic resonance imaging is presently considered the most appropriate diagnostic technique for the evaluation of vertebral alterations, as it allows to detect not only the exact morphology of the lesions, but also the pattern of bone marrow infiltration by the disease. Multiple treatment modalities can be used to manage multiple myeloma-related vertebral lesions. Surgery or radiotherapy is mainly employed in case of spinal cord compression, impending fractures, or intractable pain. Percutaneous vertebroplasty or balloon kyphoplasty can reduce local pain in a significant fraction of treated patients, without interfering with subsequent therapeutic programs. Systemic antimyeloma therapy with conventional chemotherapy or, more appropriately, with combinations of conventional chemotherapy and compounds acting on both neoplastic plasma cells and bone marrow microenvironment must be soon initiated in order to reduce bone resorption and, possibly, promote bone formation. Bisphosphonates should also be used in combination with antimyeloma therapy as they reduce bone resorption and prolong patients survival. A multidisciplinary approach is thus needed in order to properly manage spinal involvement in multiple myeloma. PMID:24381787

Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma.

PubMed

Simonsen, Trude G; Gaustad, Jon-Vidar; Rofstad, Einar K

2016-06-01

A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Health care administrators' perspectives on the role of absorptive capacity for strategic change initiatives: a qualitative study.

PubMed

Kash, Bita A; Spaulding, Aaron; Gamm, Larry; Johnson, Christopher E

2013-01-01

The dimensions of absorptive capacity (ACAP) are defined, and the importance of ACAP is established in the management literature, but the concept has not been applied to health care organizations attempting to implement multiple strategic initiatives. The aim of this study was to test the utility of ACAP by analyzing health care administrators' experiences with multiple strategic initiatives within two health systems. Results are drawn from administrators' assessments of multiple initiatives within two health systems using in-depth personal interviews with a total of 61 health care administrators. Data analysis was performed following deductive qualitative analysis guidelines. Interview transcripts were coded based on the four dimensions of ACAP: acquiring, assimilating, internalizing/transforming, and exploiting knowledge. Furthermore, we link results related to utilization of management resources, including number of key personnel involved and time consumption, to dimensions of ACAP. Participants' description of multiple strategic change initiatives confirmed the importance of the four ACAP dimensions. ACAP can be a useful framework to assess organizational capacity with respect to the organization's ability to concurrently implement multiple strategic initiatives. This capacity specifically revolves around human capital requirements from upper management based on the initiatives' location or stage within the ACAP framework. Strategic change initiatives in health care can be usefully viewed from an ACAP perspective. There is a tendency for those strategic initiatives ranking higher in priority and time consumption to reflect more advanced dimensions of ACAP (assimilate and transform), whereas few initiatives were identified in the ACAP "exploit" dimension. This may suggest that health care leaders tend to no longer identify as strategic initiatives those innovations that have moved to the exploitation stage or that less attention is given to the exploitation elements of a strategic initiative than to the earlier stages.

AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform

PubMed Central

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

Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

PubMed Central

Gizzi, Alessio; Cherry, Elizabeth M.; Gilmour, Robert F.; Luther, Stefan; Filippi, Simonetta; Fenton, Flavio H.

2013-01-01

Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events. PMID:23637684

MULTIPLE NONSPECIFIC SITES OF JOINT PAIN OUTSIDE THE KNEES DEVELOP IN PERSONS WITH KNEE PAIN

PubMed Central

Felson, David T.; Niu, Jingbo; Quinn, Emily K; Neogi, Tuhina; Lewis, Cara; Lewis, Cora E.; Law, Laura Frey; McCulloch, Chuck; Nevitt, Michael; LaValley, Michael

2017-01-01

Objective Many persons with knee pain have joint pain outside the knee but despite the impact and high frequency of this pain, its distribution and causes have not been studied. Those studying gait abnormalities have suggested that knee pain causes pain in adjacent joints but pain adaptation strategies are highly individualized. Methods We studied persons age 50-79 years with or at high risk of knee osteoarthritis drawn from two community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative and followed for 5-7 years. We excluded those with knee pain at baseline and compared those who developed and did not develop knee pain at the first follow-up examination (the index visit). We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint specific pain adjusted for age, sex, BMI, depression with sensitivity analyses excluding those with widespread pain. Results In the combined cohorts, there were 693 persons with index visit knee pain vs. 2793 without it. 79.6% of those with bilateral and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee vs. 49.9% of those without knee pain. An increased risk of pain was present in most extremity joint sites without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded. Conclusions Persons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern. PMID:27589036

AccrualNet: Addressing Low Accrual Via a Knowledge-Based, Community of Practice Platform.

PubMed

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.

Unmanned Aircraft Systems (UAS) Traffic Management (UTM) National Campaign II

NASA Technical Reports Server (NTRS)

Aweiss, Arwa S.; Owens, Brandon D.; Rios, Joseph L.; Homola, Jeffrey R.; Mohlenbrink, Christoph P.

2018-01-01

The Unmanned Aircraft System (UAS) Traffic Management (UTM) effort at NASA aims to enable access to low-altitude airspace for small UAS. This goal is being pursued partly through partnerships that NASA has developed with the UAS stakeholder community, the FAA, other government agencies, and the designated FAA UAS Test Sites. By partnering with the FAA UAS Test Sites, NASA's UTM project has performed a geographically diverse, simultaneous set of UAS operations at locations in six states. The demonstrations used an architecture that was developed by NASA in partnership with the FAA to safely coordinate such operations. These demonstrations-the second or 'Technical Capability Level (TCL 2)' National Campaign of UTM testing-was performed from May 15 through June 9, 2017. Multiple UAS operations occurred during the testing at sites located in Alaska, Nevada, Texas, North Dakota, Virginia, and New York with multiple organizations serving as UAS Service Suppliers and/or UAS Operators per the specifications provided by NASA. By engaging various members of the UAS community in development and operational roles, this campaign provided initial validation of different aspects of the UTM concept including: UAS Service Supplier technologies and procedures; geofencing technologies/conformance monitoring; ground-based surveillance/sense and avoid; airborne sense and avoid; communication, navigation, surveillance; and human factors related to UTM data creation and display. Additionally, measures of performance were defined and calculated from the flight data to establish quantitative bases for comparing flight test activities and to provide potential metrics that might be routinely monitored in future operational UTM systems.

Fire Severity and Soil Carbon Combustion in Boreal and Tundra Ecosystems

NASA Astrophysics Data System (ADS)

Walker, X. J.; Mack, M. C.; Baltzer, J. L.; Cummings, S.; Day, N.; Goetz, S.; Johnstone, J. F.; Rogers, B. M.; Turetsky, M. R.

2016-12-01

Climate warming in northern latitudes has led to an intensification of wildfire disturbance. Increased fire frequency, extent, and severity is expected to strongly impact the structure and function of northern ecosystems. In this study, we examined 50 sites in a recently burned tundra ecosystem of Alaska, USA and 250 sites in recently burned boreal conifer forest ecosystems of Northwest Territories, Canada. The majority of organic carbon (C) in both boreal and tundra ecosystems resides in the soil organic layer (SOL) and combustion of this layer can lead to large C emissions. Through examining multiple fire scars in different regions, ranging in moisture, elevation, and pre-fire vegetation communities, we can determine the ecosystem, landscape, and regional controls on SOL combustion and the potential shift in C storage. In this research, we use scalable SOL consumption metrics to estimate depth of burn and the associated C emissions. Preliminary results from boreal conifer sites indicate that nearly 50% of the pre-fire soil C pool was combusted and that over 75% of the total C emitted from the extreme fire year of 2014 can be attributed to combustion of the SOL. Increased combustion of SOL associated with an intensifying fire regime could shift boreal and tundra ecosystems across a C cycle threshold: from net accumulation of C from the atmosphere over multiple fire cycles, to a net loss. Understanding changes in SOL combustion and C storage is essential for assessing the consequences of an altered fire regime on permafrost dynamics, vegetation regeneration, and the initiation of successional trajectories in tundra and boreal ecosystems.

Management of Globally Distributed Software Development Projects in Multiple-Vendor Constellations

NASA Astrophysics Data System (ADS)

Schott, Katharina; Beck, Roman; Gregory, Robert Wayne

Global information systems development outsourcing is an apparent trend that is expected to continue in the foreseeable future. Thereby, IS-related services are not only increasingly provided from different geographical sites simultaneously but beyond that from multiple service providers based in different countries. The purpose of this paper is to understand how the involvement of multiple service providers affects the management of the globally distributed information systems development projects. As research on this topic is scarce, we applied an exploratory in-depth single-case study design as research approach. The case we analyzed comprises a global software development outsourcing project initiated by a German bank together with several globally distributed vendors. For data collection and data analysis we have adopted techniques suggested by the grounded theory method. Whereas the extant literature points out the increased management overhead associated with multi-sourcing, the analysis of our case suggests that the required effort for managing global outsourcing projects with multiple vendors depends among other things on the maturation level of the cooperation within the vendor portfolio. Furthermore, our data indicate that this interplay maturity is positively impacted through knowledge about the client that has been derived based on already existing client-vendor relationships. The paper concludes by offering theoretical and practical implications.

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study.

PubMed

Tewarie, Prejaas; Steenwijk, Martijn D; Brookes, Matthew J; Uitdehaag, Bernard M J; Geurts, Jeroen J G; Stam, Cornelis J; Schoonheim, Menno M

2018-06-01

To understand the heterogeneity of functional connectivity results reported in the literature, we analyzed the separate effects of grey and white matter damage on functional connectivity and networks in multiple sclerosis. For this, we employed a biophysical thalamo-cortical model consisting of interconnected cortical and thalamic neuronal populations, informed and amended by empirical diffusion MRI tractography data, to simulate functional data that mimic neurophysiological signals. Grey matter degeneration was simulated by decreasing within population connections and white matter degeneration by lowering between population connections, based on lesion predilection sites in multiple sclerosis. For all simulations, functional connectivity and functional network organization are quantified by phase synchronization and network integration, respectively. Modeling results showed that both cortical and thalamic grey matter damage induced a global increase in functional connectivity, whereas white matter damage induced an initially increased connectivity followed by a global decrease. Both white and especially grey matter damage, however, induced a decrease in network integration. These empirically informed simulations show that specific topology and timing of structural damage are nontrivial aspects in explaining functional abnormalities in MS. Insufficient attention to these aspects likely explains contradictory findings in multiple sclerosis functional imaging studies so far. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies

PubMed Central

von Kalckreuth, Vera; Konings, Frank; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Breiman, Robert F.; Bjerregaard-Andersen, Morten; Clemens, John D.; Crump, John A.; Cruz Espinoza, Ligia Maria; Deerin, Jessica Fung; Gasmelseed, Nagla; Sow, Amy Gassama; Im, Justin; Keddy, Karen H.; Cosmas, Leonard; May, Jürgen; Meyer, Christian G.; Mintz, Eric D.; Montgomery, Joel M.; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Rakotozandrindrainy, Raphaël; Schütt-Gerowitt, Heidi; Soura, Abdramane Bassiahi; Warren, Michelle R.; Wierzba, Thomas F.; Marks, Florian

2016-01-01

Background. New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Methods. Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Results. Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. Conclusions. By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs. PMID:26933028

Effect of the Drilling Technique on Heat Generation During Osteotomy Preparation for Wide-Diameter Implants.

PubMed

El-Kholey, Khalid E; Elkomy, Aamna

2016-12-01

To test the hypothesis that there would be no difference in heat generation by reducing the number of drills during the implant site preparation relative to conventional drilling sequence. A total of 80 implant site preparations with 2 different diameters (5.6 and 6.2 mm) were performed on bovine ribs. Within the same diameter group, half of the preparations were performed by a simplified drilling procedure (pilot drill + final diameter drill) and the other half using the conventional drilling protocol, where multiple drills of increasing diameter were utilized. Heat production by different drilling techniques was evaluated by measuring the bone temperature using K-type thermocouple and a sensitive thermometer before and after each drill. Mean for maximum temperature increase during site preparation of the 5.6- and 6.2-mm implants was 2.20°C, and it was 2.55°C when the site was prepared by the simplified procedure, whereas it was 2.80°C and 2.95°C for the sites prepared by the conventional technique, respectively. No significant difference in temperature increase was found when implants of the 2 chosen diameters were prepared either by the conventional or simplified drilling procedure. The simplified drilling protocol produces similar amount of heat comparable to the conventional technique, which proved the initial hypothesis.

Unveiled: Interrogating the Use of Applied Drama in Multiple and Specific Sites

ERIC Educational Resources Information Center

Daboo, Jerri

2007-01-01

This article examines a view of site through postcolonial feminism to suggest that multiple and contradictory discourses of culture, location, gender and context are all vital in an understanding of a specific site when working with a community. These views are applied to a project undertaken with a group of Asian women in Britain exploring issues…

Geospatial Optimization of Siting Large-Scale Solar Projects

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

Macknick, Jordan; Quinby, Ted; Caulfield, Emmet

2014-03-01

Recent policy and economic conditions have encouraged a renewed interest in developing large-scale solar projects in the U.S. Southwest. However, siting large-scale solar projects is complex. In addition to the quality of the solar resource, solar developers must take into consideration many environmental, social, and economic factors when evaluating a potential site. This report describes a proof-of-concept, Web-based Geographical Information Systems (GIS) tool that evaluates multiple user-defined criteria in an optimization algorithm to inform discussions and decisions regarding the locations of utility-scale solar projects. Existing siting recommendations for large-scale solar projects from governmental and non-governmental organizations are not consistent withmore » each other, are often not transparent in methods, and do not take into consideration the differing priorities of stakeholders. The siting assistance GIS tool we have developed improves upon the existing siting guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.« less

Instantaneous network RTK in Orange County, California

NASA Astrophysics Data System (ADS)

Bock, Y.

2003-04-01

The Orange County Real Time GPS Network (OCRTN) is an upgrade of a sub-network of SCIGN sites in southern California to low latency (1-2 sec), high-rate (1 Hz) data streaming, analysis, and dissemination. The project is a collaborative effort of the California Spatial Reference Center (CSRC) and the Orange County Public Resource and Facilities Division, with partners from the geophysical community, local and state government, and the private sector. Currently, ten sites are streaming 1 Hz raw data (Ashtech binary MBEN format) by means of dedicated, point-to-point radio modems to a network hub that translates the asynchronous serial data to TCP/IP and onto a PC workstation residing on a local area network. Software residing on the PC allows multiple clients to access the raw data simultaneously though TCP/IP. One of the clients is a Geodetics RTD server that receives and archives (1) the raw 1 Hz network data, (2) estimates of instantaneous positions and zenith tropospheric delays for quality control and detection of ground motion, and (3) RINEX data to decimated to 30 seconds. Data recovery is typically 99-100%. The server also produces 1 Hz RTCM data (messages 18, 19, 3 and 22) that are available by means of TCP/IP to RTK clients with wireless Internet modems. Coverage is excellent throughout the county. The server supports standard RTK users and is compatible with existing GPS instrumentation. Typical latency is 1-2 s, with initialization times of several seconds to minutes OCRTN site spacing is 10-15 km. In addition, the server supports “smart clients” who can retrieve data from the closest n sites (typically 3) and obtain an instantaneous network RTK position with 1-2 s latency. This mode currently requires a PDA running the RTD client software, and a wireless card. Since there is no initialization and re-initialization required this approach is well suited to support high-precision (centimeter-level) dynamic applications such as intelligent transportation and aircraft landing. We will discuss the results of field tests of this system, indicating that instantaneous network RTK can be performed accurately and reliably. If an Internet connection is available we will present a real-time demonstration.

Resuscitative endovascular balloon occlusion of the aorta may increase the bleeding of minor thoracic injury in severe multiple trauma patients: a case report.

PubMed

Maruhashi, Takaaki; Minehara, Hiroaki; Takeuchi, Ichiro; Kataoka, Yuichi; Asari, Yasushi

2017-12-14

The resuscitative endovascular balloon occlusion of the aorta, because of its efficacy and feasibility, has been widely used in treating patients with severe torso trauma. However, complications developing around the site proximal to the occlusion by resuscitative endovascular balloon occlusion of the aorta have almost never been studied. A 50-year-old Japanese woman fell from a height of approximately 10 m. At initial arrival, her respiratory rate was 24 breaths/minute, her blood oxygen saturation was 95% under 10 L/minute oxygenation, her pulse rate was 90 beats per minute, and her blood pressure was 180/120 mmHg. Mild lung contusion, hemopneumothorax, unstable pelvic fracture, and retroperitoneal bleeding with extravasation of contrast media were observed in initial computed tomography. As her vital signs had deteriorated during computed tomography, a 7-French aortic occlusion catheter (RESCUE BALLOON®, Tokai Medical Products, Aichi, Japan) was inserted and inflated for aortic occlusion at the first lumbar vertebra level and transcatheter arterial embolization was performed for the pelvic fracture. Her bilateral internal iliac arteries were embolized with a gelatin sponge; however, the embolized sites presented recanalization as coagulopathy appeared. Her bilateral internal iliac arteries were re-embolized by n-butyl-2-cyanoacrylate. The balloon was deflated 18 minutes later. After embolization, repeat computed tomography was performed and a massive hemothorax, which had not been captured on arrival, had appeared in her left pleural cavity. Thoracotomy hemostasis was performed and a hemothorax of approximately 2500 ml was aspirated to search for the source of bleeding. However, clear active bleeding was not captured; resuscitative endovascular balloon occlusion of the aorta may have been the cause of the increased bleeding of the thoracic injury at the proximal site of the aorta occlusion. It is necessary to note that the use of resuscitative endovascular balloon occlusion of the aorta may increase bleeding in sites proximal to occlusions, even in the case of minor injuries without active bleeding at the initial diagnosis.

Molecular Modeling and Imaging of Initial Stages of Cellulose Fibril Assembly: Evidence for a Disordered Intermediate Stage

PubMed Central

Haigler, Candace H.; Grimson, Mark J.; Gervais, Julien; Le Moigne, Nicolas; Höfte, Herman; Monasse, Bernard; Navard, Patrick

2014-01-01

The remarkable mechanical strength of cellulose reflects the arrangement of multiple β-1,4-linked glucan chains in a para-crystalline fibril. During plant cellulose biosynthesis, a multimeric cellulose synthesis complex (CSC) moves within the plane of the plasma membrane as many glucan chains are synthesized from the same end and in close proximity. Many questions remain about the mechanism of cellulose fibril assembly, for example must multiple catalytic subunits within one CSC polymerize cellulose at the same rate? How does the cellulose fibril bend to align horizontally with the cell wall? Here we used mathematical modeling to investigate the interactions between glucan chains immediately after extrusion on the plasma membrane surface. Molecular dynamics simulations on groups of six glucans, each originating from a position approximating its extrusion site, revealed initial formation of an uncrystallized aggregate of chains from which a protofibril arose spontaneously through a ratchet mechanism involving hydrogen bonds and van der Waals interactions between glucose monomers. Consistent with the predictions from the model, freeze-fracture transmission electron microscopy using improved methods revealed a hemispherical accumulation of material at points of origination of apparent cellulose fibrils on the external surface of the plasma membrane where rosette-type CSCs were also observed. Together the data support the possibility that a zone of uncrystallized chains on the plasma membrane surface buffers the predicted variable rates of cellulose polymerization from multiple catalytic subunits within the CSC and acts as a flexible hinge allowing the horizontal alignment of the crystalline cellulose fibrils relative to the cell wall. PMID:24722535

77 FR 28240 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... multiple site damage cracks in the radial web lap and tear strap splices of the aft pressure bulkhead at... multiple site damage cracks in the radial web lap and tear strap splices of the aft pressure bulkhead at...

Large-area experiment on uptake of metals by twelve plants growing in soils contaminated with multiple metals.

PubMed

Lai, Hung-Yu; Juang, Kai-Wei; Chen, Zueng-Sang

2010-01-01

A site in central Taiwan with an area of 1.3 ha and contaminated with Cr, Cu, Ni, and Zn was selected to examine the feasibility of phytoextraction. Based on the results of a preexperiment at this site, a total of approximately 20,000 plants of 12 species were selected from plants of 33 tested species to be used in a large-area phytoextraction experiment at this site. A comparison with the initial metal concentration of 12 plant species before planting demonstrated that most species accumulated significant amounts of Cr, Cu, Ni, and Zn in their shoots after growing in this contaminated site for 31 d. Among the 12 plant species, the following accumulated higher concentrations of metals in their shoots; Garden canna and Garden verbena (45-60 mg Cr kg(-1)), Chinese ixora and Kalanchoe (30 mg Cu kg(-1)), Rainbow pink and Sunflower (30 mg Ni kg(-1)), French marigold and Sunflower (300-470 mg Zn kg(-1)). The roots of the plants of most of the 12 plant species can accumulate higher concentrations of metals than the shoots and extending the growth period promotes accumulation in the shoots. Large-area experiments demonstrated that phytoextraction is a feasible method to enable metal-contaminated soil in central Taiwan to be reused.

Accumulation of impact markers in desert wetlands and implications for the Younger Dryas impact hypothesis.

PubMed

Pigati, Jeffrey S; Latorre, Claudio; Rech, Jason A; Betancourt, Julio L; Martínez, Katherine E; Budahn, James R

2012-05-08

The Younger Dryas impact hypothesis contends that an extraterrestrial object exploded over North America at 12.9 ka, initiating the Younger Dryas cold event, the extinction of many North American megafauna, and the demise of the Clovis archeological culture. Although the exact nature and location of the proposed impact or explosion remain unclear, alleged evidence for the fallout comes from multiple sites across North America and a site in Belgium. At 6 of the 10 original sites (excluding the Carolina Bays), elevated concentrations of various "impact markers" were found in association with black mats that date to the onset of the Younger Dryas. Black mats are common features in paleowetland deposits and typically represent shallow marsh environments. In this study, we investigated black mats ranging in age from approximately 6 to more than 40 ka in the southwestern United States and the Atacama Desert of northern Chile. At 10 of 13 sites, we found elevated concentrations of iridium in bulk and magnetic sediments, magnetic spherules, and/or titanomagnetite grains within or at the base of black mats, regardless of their age or location, suggesting that elevated concentrations of these markers arise from processes common to wetland systems, and not a catastrophic extraterrestrial impact event.

Accumulation of impact markers in desert wetlands and implications for the Younger Dryas impact hypothesis

PubMed Central

Pigati, Jeffrey S.; Latorre, Claudio; Rech, Jason A.; Betancourt, Julio L.; Martínez, Katherine E.; Budahn, James R.

2012-01-01

The Younger Dryas impact hypothesis contends that an extraterrestrial object exploded over North America at 12.9 ka, initiating the Younger Dryas cold event, the extinction of many North American megafauna, and the demise of the Clovis archeological culture. Although the exact nature and location of the proposed impact or explosion remain unclear, alleged evidence for the fallout comes from multiple sites across North America and a site in Belgium. At 6 of the 10 original sites (excluding the Carolina Bays), elevated concentrations of various “impact markers” were found in association with black mats that date to the onset of the Younger Dryas. Black mats are common features in paleowetland deposits and typically represent shallow marsh environments. In this study, we investigated black mats ranging in age from approximately 6 to more than 40 ka in the southwestern United States and the Atacama Desert of northern Chile. At 10 of 13 sites, we found elevated concentrations of iridium in bulk and magnetic sediments, magnetic spherules, and/or titanomagnetite grains within or at the base of black mats, regardless of their age or location, suggesting that elevated concentrations of these markers arise from processes common to wetland systems, and not a catastrophic extraterrestrial impact event. PMID:22529347

Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

NASA Astrophysics Data System (ADS)

Viswanathan, Kavitha; Dhabhar, Firdaus S.

2005-04-01

Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

Pilot-Scale Demonstration of In-Situ Chemical Oxidation ...

EPA Pesticide Factsheets

A pilot-scale in situ chemical oxidation (ISCO) demonstration, involving subsurface injections of sodium permanganate (NaMnO4), was performed at the US Marine Corp Recruit Depot (MCRD), site 45 (Parris Island (PI), SC). The ground water was originally contaminated with perchloroethylene (PCE) (also known as tetrachloroethylene), a chlorinated solvent used in dry cleaner operations. High resolution site characterization involved multiple iterations of soil core sampling and analysis. Nested micro-wells and conventional wells were also used to sample and analyze ground water for PCE and decomposition products (i.e., trichloroethyelene (TCE), dichloroethylene (c-DCE, t-DCE), and vinyl chloride (VC)), collectively referred to as chlorinated volatile organic compounds (CVOC). This characterization methodology was used to develop and refine the conceptual site model and the ISCO design, not only by identifying CVOC contamination but also by eliminating uncontaminated portions of the aquifer from further ISCO consideration. Direct-push injection was selected as the main method of NaMnO4 delivery due to its flexibility and low initial capital cost. Site impediments to ISCO activities in the source area involved subsurface utilities, including a high pressure water main, a high voltage power line, a communication line, and sanitary and stormwater sewer lines. Utility markings were used in conjunction with careful planning and judicious selection of injection locations. A

Multiscale Processes in Magnetic Reconnection

NASA Astrophysics Data System (ADS)

Surjalal Sharma, A.; Jain, Neeraj

The characteristic scales of the plasma processes in magnetic reconnection range from the elec-tron skin-depth to the magnetohydrodynamic (MHD) scale, and cross-scale coupling among them play a key role. Modeling these processes requires different physical models, viz. kinetic, electron-magnetohydrodynamics (EMHD), Hall-MHD, and MHD. The shortest scale processes are at the electron scale and these are modeled using an EMHD code, which provides many features of the multiscale behavior. In simulations using initial conditions consisting of pertur-bations with many scale sizes the reconnection takes place at many sites and the plasma flows from these interact with each other. This leads to thin current sheets with length less than 10 electron skin depths. The plasma flows also generate current sheets with multiple peaks, as observed by Cluster. The quadrupole structure of the magnetic field during reconnection starts on the electron scale and the interaction of inflow to the secondary sites and outflow from the dominant site generates a nested structure. In the outflow regions, the interaction of the electron outflows generated at the neighboring sites lead to the development of electron vortices. A signature of the nested structure of the Hall field is seen in Cluster observations, and more details of these features are expected from MMS.

Accumulation of impact markers in desert wetlands and implications for the Younger Dryas impact hypothesis

USGS Publications Warehouse

Pigati, Jeffrey S.; Latorre, Claudio; Rech, Jason A.; Betancourt, Julio L.; Martinez, Katherine E.; Budahn, James R.

2012-01-01

The Younger Dryas impact hypothesis contends that an extraterrestrial object exploded over North America at 12.9 ka, initiating the Younger Dryas cold event, the extinction of many North American megafauna, and the demise of the Clovis archeological culture. Although the exact nature and location of the proposed impact or explosion remain unclear, alleged evidence for the fallout comes from multiple sites across North America and a site in Belgium. At 6 of the 10 original sites (excluding the Carolina Bays), elevated concentrations of various "impact markers" were found in association with black mats that date to the onset of the Younger Dryas. Black mats are common features in paleowetland deposits and typically represent shallow marsh environments. In this study, we investigated black mats ranging in age from approximately 6 to more than 40 ka in the southwestern United States and the Atacama Desert of northern Chile. At 10 of 13 sites, we found elevated concentrations of iridium in bulk and magnetic sediments, magnetic spherules, and/or titanomagnetite grains within or at the base of black mats, regardless of their age or location, suggesting that elevated concentrations of these markers arise from processes common to wetland systems, and not a catastrophic extraterrestrial impact event.

Endogenous Hot Spots of De Novo Telomere Addition in the Yeast Genome Contain Proximal Enhancers That Bind Cdc13

PubMed Central

Obodo, Udochukwu C.; Epum, Esther A.; Platts, Margaret H.; Seloff, Jacob; Dahlson, Nicole A.; Velkovsky, Stoycho M.; Paul, Shira R.

2016-01-01

DNA double-strand breaks (DSBs) pose a threat to genome stability and are repaired through multiple mechanisms. Rarely, telomerase, the enzyme that maintains telomeres, acts upon a DSB in a mutagenic process termed telomere healing. The probability of telomere addition is increased at specific genomic sequences termed sites of repair-associated telomere addition (SiRTAs). By monitoring repair of an induced DSB, we show that SiRTAs on chromosomes V and IX share a bipartite structure in which a core sequence (Core) is directly targeted by telomerase, while a proximal sequence (Stim) enhances the probability of de novo telomere formation. The Stim and Core sequences are sufficient to confer a high frequency of telomere addition to an ectopic site. Cdc13, a single-stranded DNA binding protein that recruits telomerase to endogenous telomeres, is known to stimulate de novo telomere addition when artificially recruited to an induced DSB. Here we show that the ability of the Stim sequence to enhance de novo telomere addition correlates with its ability to bind Cdc13, indicating that natural sites at which telomere addition occurs at high frequency require binding by Cdc13 to a sequence 20 to 100 bp internal from the site at which telomerase acts to initiate de novo telomere addition. PMID:27044869

Reduction of pain via platelet-rich plasma in split-thickness skin graft donor sites: a series of matched pairs

PubMed Central

Miller, John D.; Rankin, Timothy M.; Hua, Natalie T.; Ontiveros, Tina; Giovinco, Nicholas A.; Mills, Joseph L.; Armstrong, David G.

2015-01-01

In the past decade, autologous platelet-rich plasma (PRP) therapy has seen increasingly widespread integration into medical specialties. PRP application is known to accelerate wound epithelialization rates, and may also reduce postoperative wound site pain. Recently, we observed an increase in patient satisfaction following PRP gel (Angel, Cytomedix, Rockville, MD) application to split-thickness skin graft (STSG) donor sites. We assessed all patients known to our university-based hospital service who underwent multiple STSGs up to the year 2014, with at least one treated with topical PRP. Based on these criteria, five patients aged 48.4±17.6 (80% male) were identified who could serve as their own control, with mean time of 4.4±5.1 years between operations. In both therapies, initial dressing changes occurred on postoperative day (POD) 7, with donor site pain measured by Likert visual pain scale. Paired t-tests compared the size and thickness of harvested skin graft and patient pain level, and STSG thickness and surface area were comparable between control and PRP interventions (p>0.05 for all). Donor site pain was reduced from an average of 7.2 (±2.6) to 3 (±3.7), an average reduction in pain of 4.2 (standard error 1.1, p=0.0098) following PRP use. Based on these results, the authors suggest PRP as a beneficial adjunct for reducing donor site pain following STSG harvest. PMID:25623477

An integrated approach to assess broad-scale condition of coastal wetlands - The Gulf of Mexico Coastal Wetlands pilot survey

USGS Publications Warehouse

Nestlerode, J.A.; Engle, V.D.; Bourgeois, P.; Heitmuller, P.T.; Macauley, J.M.; Allen, Y.C.

2009-01-01

The Environmental Protection Agency (EPA) and U.S. Geological Survey (USGS) initiated a two-year regional pilot survey in 2007 to develop, test, and validate tools and approaches to assess the condition of northern Gulf of Mexico (GOM) coastal wetlands. Sampling sites were selected from estuarine and palustrine wetland areas with herbaceous, forested, and shrub/scrub habitats delineated by the US Fish and Wildlife Service National Wetlands Inventory Status and Trends (NWI S&T) program and contained within northern GOM coastal watersheds. A multi-level, stepwise, iterative survey approach is being applied to multiple wetland classes at 100 probabilistically-selected coastal wetlands sites. Tier 1 provides information at the landscape scale about habitat inventory, land use, and environmental stressors associated with the watershed in which each wetland site is located. Tier 2, a rapid assessment conducted through a combination of office and field work, is based on best professional judgment and on-site evidence. Tier 3, an intensive site assessment, involves on-site collection of vegetation, water, and sediment samples to establish an integrated understanding of current wetland condition and validate methods and findings from Tiers 1 and 2. The results from this survey, along with other similar regional pilots from the Mid-Atlantic, West Coast, and Great Lakes Regions will contribute to a design and implementation approach for the National Wetlands Condition Assessment to be conducted by EPA's Office of Water in 2011. ?? Springer Science+Business Media B.V. 2008.

Using network screening methods to determine locations with specific safety issues: A design consistency case study.

PubMed

Butsick, Andrew J; Wood, Jonathan S; Jovanis, Paul P

2017-09-01

The Highway Safety Manual provides multiple methods that can be used to identify sites with promise (SWiPs) for safety improvement. However, most of these methods cannot be used to identify sites with specific problems. Furthermore, given that infrastructure funding is often specified for use related to specific problems/programs, a method for identifying SWiPs related to those programs would be very useful. This research establishes a method for Identifying SWiPs with specific issues. This is accomplished using two safety performance functions (SPFs). This method is applied to identifying SWiPs with geometric design consistency issues. Mixed effects negative binomial regression was used to develop two SPFs using 5 years of crash data and over 8754km of two-lane rural roadway. The first SPF contained typical roadway elements while the second contained additional geometric design consistency parameters. After empirical Bayes adjustments, sites with promise (SWiPs) were identified. The disparity between SWiPs identified by the two SPFs was evident; 40 unique sites were identified by each model out of the top 220 segments. By comparing sites across the two models, candidate road segments can be identified where a lack design consistency may be contributing to an increase in expected crashes. Practitioners can use this method to more effectively identify roadway segments suffering from reduced safety performance due to geometric design inconsistency, with detailed engineering studies of identified sites required to confirm the initial assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Continuum mesoscopic framework for multiple interacting species and processes on multiple site types and/or crystallographic planes.

PubMed

Chatterjee, Abhijit; Vlachos, Dionisios G

2007-07-21

While recently derived continuum mesoscopic equations successfully bridge the gap between microscopic and macroscopic physics, so far they have been derived only for simple lattice models. In this paper, general deterministic continuum mesoscopic equations are derived rigorously via nonequilibrium statistical mechanics to account for multiple interacting surface species and multiple processes on multiple site types and/or different crystallographic planes. Adsorption, desorption, reaction, and surface diffusion are modeled. It is demonstrated that contrary to conventional phenomenological continuum models, microscopic physics, such as the interaction potential, determines the final form of the mesoscopic equation. Models of single component diffusion and binary diffusion of interacting particles on single-type site lattice and of single component diffusion on complex microporous materials' lattices consisting of two types of sites are derived, as illustrations of the mesoscopic framework. Simplification of the diffusion mesoscopic model illustrates the relation to phenomenological models, such as the Fickian and Maxwell-Stefan transport models. It is demonstrated that the mesoscopic equations are in good agreement with lattice kinetic Monte Carlo simulations for several prototype examples studied.

Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

PubMed

Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

2016-02-01

Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed.

40 CFR 63.6610 - By what date must I conduct the initial performance tests or other initial compliance...

Code of Federal Regulations, 2010 CFR

2010-07-01

... initial performance tests or other initial compliance demonstrations if I own or operate a stationary RICE... performance tests or other initial compliance demonstrations if I own or operate a stationary RICE with a site... stationary RICE with a site rating of more than 500 brake HP located at a major source of HAP emissions you...

40 CFR 63.6610 - By what date must I conduct the initial performance tests or other initial compliance...

Code of Federal Regulations, 2011 CFR

2011-07-01

... initial performance tests or other initial compliance demonstrations if I own or operate a stationary RICE... performance tests or other initial compliance demonstrations if I own or operate a stationary RICE with a site... stationary RICE with a site rating of more than 500 brake HP located at a major source of HAP emissions you...

Modeling Complex Equilibria in ITC Experiments: Thermodynamic Parameters Estimation for a Three Binding Site Model

PubMed Central

Le, Vu H.; Buscaglia, Robert; Chaires, Jonathan B.; Lewis, Edwin A.

2013-01-01

Isothermal Titration Calorimetry, ITC, is a powerful technique that can be used to estimate a complete set of thermodynamic parameters (e.g. Keq (or ΔG), ΔH, ΔS, and n) for a ligand binding interaction described by a thermodynamic model. Thermodynamic models are constructed by combination of equilibrium constant, mass balance, and charge balance equations for the system under study. Commercial ITC instruments are supplied with software that includes a number of simple interaction models, for example one binding site, two binding sites, sequential sites, and n-independent binding sites. More complex models for example, three or more binding sites, one site with multiple binding mechanisms, linked equilibria, or equilibria involving macromolecular conformational selection through ligand binding need to be developed on a case by case basis by the ITC user. In this paper we provide an algorithm (and a link to our MATLAB program) for the non-linear regression analysis of a multiple binding site model with up to four overlapping binding equilibria. Error analysis demonstrates that fitting ITC data for multiple parameters (e.g. up to nine parameters in the three binding site model) yields thermodynamic parameters with acceptable accuracy. PMID:23262283

Tomographic phase analysis to detect the site of accessory conduction pathway in Wolff-Parkinson-White syndrome

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

Nakajima, K.; Bunko, H.; Tada, A.

1984-01-01

Phase analysis has been applied to Wolff-Parkinson-White syndrome (WPW) to detect the site of accessory conduction pathway (ACP); however, there was a limitation to estimate the precise location of ACP by planar phase analysis. In this study, the authors applied phase analysis to gated blood pool tomography. Twelve patients with WPW who underwent epicardial mapping and surgical division of ACP were studied by both of gated emission computed tomography (GECT) and routine gated blood pool study (GBPS). The GBPS was performed with Tc-99m red blood cells in multiple projections; modified left anterior oblique, right anterior oblique and/or left lateral views.more » In GECT, short axial, horizontal and vertical long axial blood pool images were reconstructed. Phase analysis was performed using fundamental frequency of the Fourier transform in both GECT and GBPS images, and abnormal initial contractions on both the planar and tomographic phase analysis were compared with the location of surgically confirmed ACPs. In planar phase analysis, abnormal initial phase was identified in 7 out of 12 (58%) patients, while in tomographic phase analysis, the localization of ACP was predicted in 11 out of 12 (92%) patients. Tomographic phase analysis is superior to planar phase images in 8 out of 12 patients to estimate the location of ACP. Phase analysis by GECT can avoid overlap of blood pool in cardiac chambers and has advantage to identify the propagation of phase three-dimensionally. Tomographic phase analysis is a good adjunctive method for patients with WPW to estimate the site of ACP.« less

Multiple bidirectional initiations and terminations of transcription in the Marek's disease virus long repeat regions.

PubMed Central

Chen, X B; Velicer, L F

1991-01-01

Marek's disease is an oncogenic disease of chickens caused by a herpesvirus, Marek's disease virus (MDV). Serial in vitro passage of pathogenic MDV results in amplification of a 132-bp direct repeat in the MDV genome's TRL and IRL repeat regions and loss of tumorigenicity. This led to the hypothesis that upon such expansion, one or more tumor-inducing genes fail to be expressed. In this report a group of cDNAs mapping in the expanded regions were isolated from a pathogenic MDV strain in which the 132-bp direct repeat number was found to range between one and seven. Partial cDNA sequencing and S1 nuclease protection analysis revealed that the corresponding transcripts are either initiated or terminated within or near the expanded regions at multiple sites in both rightward and leftward directions. Furthermore, each 132-bp repeat contains one TATA box and two polyadenylation consensus sequences in each direction. These RNAs contain a partial copy or one or more full copies of the 132-bp direct repeat at either their 5' or 3' end. Northern (RNA) blot analysis showed that the majority of transcripts are 1.8 kb in size, while the minor species range in size from 0.67 to 3.1 kb. Together, these data raise the possibility that the 132-bp direct repeat, and indirectly its copy number, may be involved in the regulation of transcriptional initiation and termination and therefore in the generation of four groups of transcripts from the TRL and IRL, although this remains to be demonstrated. Images PMID:1850022

Concept Mapping for Planning and Evaluation of a Community-Based Initiative

ERIC Educational Resources Information Center

Chiu, Korinne

2012-01-01

Community-based initiatives address community issues by providing a multi-agency approach to prevention and intervention services (Connell et al.,1995). When incorporating multiple agencies, it can be challenging to obtain multiple perspectives and gaining consensus on the priorities and direction for these initiatives. This study employed a…

Institutional transformation: An analysis of change initiatives at NSF ADVANCE institutions

NASA Astrophysics Data System (ADS)

Plummer, Ellen W.

The purpose of this study was to examine how institutional culture promoted or impeded the implementation of round one and two NSF ADVANCE initiatives designed to improve academic climates for women in science and engineering. This study was conducted in two phases. In phase one, 35 participants from 18 institutions were interviewed to answer three research questions. Participants identified a policy, process, or program designed to improve academic cultures for women in science and engineering fields. Participants also identified strategies that promoted the implementation of these efforts, and discussed factors that impeded these efforts. In phase two, site visits were conducted at two institutions to answer a fourth research question. How did institutional culture shape the design and implementation of faculty search processes? Policies, processes, and programs were implemented by participants at the institutional, departmental, and individual levels and included family friendly and dual career policies at the institutional level, improved departmental faculty search and climate improvement processes, and mentoring programs and training for department heads at the individual level. Communication and leadership strategies were key to the successful implementation of policies, processes, and programs designed to achieve institutional transformation. Communication strategies involved shaping change messages to reach varied audiences often with the argument that change efforts would improve the climate for everyone not just women faculty members. Administrative and faculty leaders from multiple levels proved important to change efforts. Institutional Transformation Institutional culture shaped initiatives to improve faculty search processes. Faculty leaders in both settings used data to persuade faculty members of the need for change. At one site, data that included national availability information was critical to advancing the change agenda. At the other site, social science data that illustrated gender bias was persuasive. Faculty members who were effective as change agents were those who were credible with their peers in that setting.

10 CFR Appendix N to Part 50 - Standardization of Nuclear Power Plant Designs: Permits To Construct and Licenses To Operate...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Construct and Licenses To Operate Nuclear Power Reactors of Identical Design at Multiple Sites N Appendix N... Construct and Licenses To Operate Nuclear Power Reactors of Identical Design at Multiple Sites Section 101... nuclear power reactors of essentially the same design to be located at different sites. 1 1 If the design...

10 CFR Appendix N to Part 50 - Standardization of Nuclear Power Plant Designs: Permits To Construct and Licenses To Operate...

Code of Federal Regulations, 2012 CFR

2012-01-01

... Construct and Licenses To Operate Nuclear Power Reactors of Identical Design at Multiple Sites N Appendix N... Construct and Licenses To Operate Nuclear Power Reactors of Identical Design at Multiple Sites Section 101... nuclear power reactors of essentially the same design to be located at different sites. 1 1 If the design...

10 CFR Appendix N to Part 50 - Standardization of Nuclear Power Plant Designs: Permits To Construct and Licenses To Operate...

Code of Federal Regulations, 2013 CFR

2013-01-01

... Construct and Licenses To Operate Nuclear Power Reactors of Identical Design at Multiple Sites N Appendix N... Construct and Licenses To Operate Nuclear Power Reactors of Identical Design at Multiple Sites Section 101... nuclear power reactors of essentially the same design to be located at different sites. 1 1 If the design...

Initial results from the Nankai Trough shallow splay and frontal thrust (IODP Expedition 316): Implications for fluid flow

NASA Astrophysics Data System (ADS)

Screaton, E.; Kimura, G.; Curewitz, D.; Scientists, E.

2008-12-01

Integrated Ocean Drilling Program (IODP) Expedition 316 examined the frontal thrust and the shallow portion of the megasplay fault offshore of the Kii peninsula, and was the third drilling expedition of the Nankai Trough Seismogenic Zone Experiment (NanTroSEIZE). NanTroSEIZE will integrate seafloor observations, drilling, and observatories to investigate the processes controlling slip along subduction zone plate boundary fault systems. Site C0004 examined a shallow portion of the splay fault system where it overrides slope basin sediments. Site C0008, located in the slope basin 1 km seaward of Site C0004, provided a reference site for the footwall sediments. Results of drilling indicate that the footwall sediments have dewatered significantly, suggesting permeable routes for fluid escape. These high-permeability pathways might be provided by coarse-grained layers within the slope sediments. In situ dewatering and multiple fluid escape paths will tend to obscure any geochemical signature of flow from depth. Sites C0006 and C0007 examined the frontal thrust system. Although poorly recovered, coarse-grained trench sediments were sampled within the footwall. These permeable sediments would be expected to allow rapid escape of any fluid pressures due to loading. At both sites, low porosities are observed at shallow depths, suggesting removal of overlying material. This observation is consistent with interpretations that the prism is unstable and currently in a period of collapse. Anomalously low temperatures were measured within boreholes at these sites. One possible explanation for the low temperatures is circulation of seawater along normal faults in the unstable prism.

Multilayer graphene as an effective corrosion protection coating for copper

NASA Astrophysics Data System (ADS)

Ravishankar, Vasumathy; Ramaprabhu, S.; Jaiswal, Manu

2018-04-01

Graphene grown by chemical vapor deposition (CVD) has been studied as a protective layer against corrosion of copper. The layer number dependence on the protective nature of graphene has been investigated using techniques such as Tafel analysis and Electroimpedance Spectroscopy. Multiple layers of graphene were achieved by wet transfer above CVD grown graphene. Though this might cause grain boundaries, the sites where corrosion is initiated, to be staggered, wet transfer inherently carries the disadvantage of tearing of graphene, as confirmed by Raman spectroscopy measurements. However, Electroimpedance Spectroscopy (EIS) reflects that graphene protected copper has a layer dependent resistance to corrosion. Decrease in corrosion current (Icorr) for graphene protected copper is presented. There is only small dependence of corrosion current on the layer number, Tafel plots clearly indicate passivation in the presence of graphene, whether it be single layer or multiple layers. Notwithstanding the crystallite size, defect free layers of graphene with staggered grain boundaries combined with passivation could offer good corrosion protection for metals.

Ferritins: dynamic management of biological iron and oxygen chemistry.

PubMed

Liu, Xiaofeng; Theil, Elizabeth C

2005-03-01

Ferritins are spherical, cage-like proteins with nanocavities formed by multiple polypeptide subunits (four-helix bundles) that manage iron/oxygen chemistry. Catalytic coupling yields diferric oxo/hydroxo complexes at ferroxidase sites in maxi-ferritin subunits (24 subunits, 480 kDa; plants, animals, microorganisms). Oxidation occurs at the cavity surface of mini-ferritins/Dps proteins (12 subunits, 240 kDa; bacteria). Oxidation products are concentrated as minerals in the nanocavity for iron-protein cofactor synthesis (maxi-ferritins) or DNA protection (mini-ferritins). The protein cage and nanocavity characterize all ferritins, although amino acid sequences diverge, especially in bacteria. Catalytic oxidation/di-iron coupling in the protein cage (maxi-ferritins, 480 kDa; plants, bacteria and animal cell-specific isoforms) or on the cavity surface (mini-ferritins/Dps proteins, 280 kDa; bacteria) initiates mineralization. Gated pores (eight or four), symmetrically arranged, control iron flow. The multiple ferritin functions combine pore, channel, and catalytic functions in compact protein structures required for life and disease response.

Malignant fibrous histiocytoma developing in irradiated sacral chordoma

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

Halpern, J.; Kopolovic, J.; Catane, R.

1984-06-15

Malignant fibrous histiocytoma (MFH), arising at the site of a sacral chordoma 8 years after massive radiotherapy, is described. Initially, the patient received 7000 rad to the sacral area and, on recurrence, 5 years later, an additional 4000 rad. Two years later, a sacral mass was noted again. Biopsy then revealed MFH; chest x-ray showed multiple lung metastases. A combination chemotherapy, consisting of cyclophosphamide, vincristine, adriamycin (doxorubicin), and DTIC, resulted in a 6 month partial response. Subsequently, the patient died because of progressive metastatic disease. At autopsy, 8 years after diagnosis, both the sacral lesion and the lung metastases provedmore » to be MFH, and no residual chordoma was found.« less

Oral Lesions: The Clue to Diagnosis of Pemphigus Vulgaris.

PubMed

Kuriachan, Diana; Suresh, Rakesh; Janardhanan, Mahija; Savithri, Vindhya

2015-01-01

Pemphigus is a group of potentially fatal dermatoses with both cutaneous and oral manifestations. Characterized by the appearance of vesicle or bullae, their manifestations in the oral cavity often precede those on the skin by many months or may remain as the only symptoms of the disease. It is therefore important that the oral manifestations of the disease are recognized on time, to make a proper diagnosis and initiate timely treatment. Here we present a case of Pemphigus Vulgaris (PV) that presented with oral lesions at multiple sites including tongue, to highlight the importance of timely recognition of the oral lesions during routine dental practice for the diagnosis and management of this disease.

Prevalence of avian haemosporidian parasites is positively related to the abundance of host species at multiple sites within a region.

PubMed

Ellis, Vincenzo A; Medeiros, Matthew C I; Collins, Michael D; Sari, Eloisa H R; Coffey, Elyse D; Dickerson, Rebecca C; Lugarini, Camile; Stratford, Jeffrey A; Henry, Donata R; Merrill, Loren; Matthews, Alix E; Hanson, Alison A; Roberts, Jackson R; Joyce, Michael; Kunkel, Melanie R; Ricklefs, Robert E

2017-01-01

Parasite prevalence is thought to be positively related to host population density owing to enhanced contagion. However, the relationship between prevalence and local abundance of multiple host species is underexplored. We surveyed birds and their haemosporidian parasites (genera Plasmodium and Haemoproteus) at multiple sites across eastern North America to test whether the prevalence of these parasites in a host species at a particular site is related to that host's local abundance. Prevalence was positively related to host abundance within most sites, although the effect was stronger and more consistent for Plasmodium than for Haemoproteus. In contrast, prevalence was not related to variation in the abundance of most individual host species among sites across the region. These results suggest that parasite prevalence partly reflects the relative abundances of host species in local assemblages. However, three nonnative host species had low prevalence despite being relatively abundant at one site, as predicted by the enemy release hypothesis.

MULTIPLE CURRENT SHEET SYSTEMS IN THE OUTER HELIOSPHERE: ENERGY RELEASE AND TURBULENCE

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

Burgess, D.; Gingell, P. W.; Matteini, L.

2016-05-01

In the outer heliosphere, beyond the solar wind termination shock, it is expected that the warped heliospheric current sheet forms a region of closely packed, multiple, thin current sheets. Such a system may be subject to the ion-kinetic tearing instability, and hence may generate magnetic islands and hot populations of ions associated with magnetic reconnection. Reconnection processes in this environment have important implications for local particle transport, and for particle acceleration at reconnection sites and in turbulence. We study this complex environment by means of three-dimensional hybrid simulations over long timescales, in order to capture the evolution from linear growthmore » of the tearing instability to a fully developed turbulent state at late times. The final state develops from the highly ordered initial state via both forward and inverse cascades. Component and spectral anisotropy in the magnetic fluctuations is present when a guide field is included. The inclusion of a population of newborn interstellar pickup protons does not strongly affect these results. Finally, we conclude that reconnection between multiple current sheets can act as an important source of turbulence in the outer heliosphere, with implications for energetic particle acceleration and propagation.« less

Sporotrichosis: An Overview and Therapeutic Options

PubMed Central

Mahajan, Vikram K.

2014-01-01

Sporotrichosis is a chronic granulomatous mycotic infection caused by Sporothrix schenckii, a common saprophyte of soil, decaying wood, hay, and sphagnum moss, that is endemic in tropical/subtropical areas. The recent phylogenetic studies have delineated the geographic distribution of multiple distinct Sporothrix species causing sporotrichosis. It characteristically involves the skin and subcutaneous tissue following traumatic inoculation of the pathogen. After a variable incubation period, progressively enlarging papulo-nodule at the inoculation site develops that may ulcerate (fixed cutaneous sporotrichosis) or multiple nodules appear proximally along lymphatics (lymphocutaneous sporotrichosis). Osteoarticular sporotrichosis or primary pulmonary sporotrichosis are rare and occur from direct inoculation or inhalation of conidia, respectively. Disseminated cutaneous sporotrichosis or involvement of multiple visceral organs, particularly the central nervous system, occurs most commonly in persons with immunosuppression. Saturated solution of potassium iodide remains a first line treatment choice for uncomplicated cutaneous sporotrichosis in resource poor countries but itraconazole is currently used/recommended for the treatment of all forms of sporotrichosis. Terbinafine has been observed to be effective in the treatment of cutaneous sporotrichosis. Amphotericin B is used initially for the treatment of severe, systemic disease, during pregnancy and in immunosuppressed patients until recovery, then followed by itraconazole for the rest of the therapy. PMID:25614735

A laboratory study of multiple site damage in fuselage lap splices

DOT National Transportation Integrated Search

1993-12-01

This report details an experimental study that was conducted to explore the causes of : fuselage lap splice multiple site damage (MSD), which has been observed in several : aging aircraft. MSD was partially responsible for the 1988 Aloha Airlines acc...

Multiple antibiotic resistant Escherichia coli from a tropical rain forest stream

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

Carrasco, C.E.; Alvarez, H.J.; Ortiz, N.

1988-12-31

High densities of fecal coliforms were obtained from a pristine site and sewage contaminated site in a tropical rain forest watershed in Puerto Rico. Confirmation of fecal coliform isolates as Escherichia coli was significantly lower than for temperate waters. Antibiotic resistance and multiple antibiotic resistance were common for isolates at both sites; however, the site receiving sewage effluent had a greater proportion of multiple antibiotic resistant isolates. R. plasmids were recovered from 4 MAR isolates, 2 from each site. All recovered plasmids were approximately 1 kilobase. The recovered plasmid were also capable of transforming E. coli HB101 in vitro. Themore » high concentrations of enterobacteriaceae, small R-plasmid size, R-plasmid transformability, and long term survival of fecal origin bacteria in tropical freshwater environments give increasing importance to adequate sewage treatment, and better indicator monitoring methods for tropical areas.« less

Presence of multiple sites containing polar material in spherical Escherichia coli cells that lack MreB.

PubMed

Nilsen, Trine; Yan, Arthur W; Gale, Gregory; Goldberg, Marcia B

2005-09-01

In rod-shaped bacteria, certain proteins are specifically localized to the cell poles. The nature of the positional information that leads to the proper localization of these proteins is unclear. In a screen for factors required for the localization of the Shigella sp. actin assembly protein IcsA to the bacterial pole, a mutant carrying a transposon insertion in mreB displayed altered targeting of IcsA. The phenotype of cells containing a transposon insertion in mreB was indistinguishable from that of cells containing a nonpolar mutation in mreB or that of wild-type cells treated with the MreB inhibitor A22. In cells lacking MreB, a green fluorescent protein (GFP) fusion to a cytoplasmic derivative of IcsA localized to multiple sites. Secreted full-length native IcsA was present in multiple faint patches on the surfaces of these cells in a pattern similar to that seen for the cytoplasmic IcsA-GFP fusion. EpsM, the polar Vibrio cholerae inner membrane protein, also localized to multiple sites in mreB cells and colocalized with IcsA, indicating that localization to multiple sites is not unique to IcsA. Our results are consistent with the requirement, either direct or indirect, for MreB in the restriction of certain polar material to defined sites within the cell and, in the absence of MreB, with the formation of ectopic sites containing polar material.

Mechanism of Intramembrane Cleavage of Alcadeins by γ-Secretase

PubMed Central

Piao, Yi; Kimura, Ayano; Urano, Satomi; Saito, Yuhki; Taru, Hidenori; Yamamoto, Tohru; Hata, Saori; Suzuki, Toshiharu

2013-01-01

Background Alcadein proteins (Alcs; Alcα, Alcβand Alcγ) are predominantly expressed in neurons, as is Alzheimer's β-amyloid (Aβ) precursor protein (APP). Both Alcs and APP are cleaved by primary α- or β-secretase to generate membrane-associated C-terminal fragments (CTFs). Alc CTFs are further cleaved by γ-secretase to secrete p3-Alc peptide along with the release of intracellular domain fragment (Alc ICD) from the membrane. In the case of APP, APP CTFβ is initially cleaved at the ε-site to release the intracellular domain fragment (AICD) and consequently the γ-site is determined, by which Aβ generates. The initial ε-site is thought to define the final γ-site position, which determines whether Aβ40/43 or Aβ42 is generated. However, initial intracellular ε-cleavage sites of Alc CTF to generate Alc ICD and the molecular mechanism that final γ-site position is determined remains unclear in Alcs. Methodology Using HEK293 cells expressing Alcs plus presenilin 1 (PS1, a catalytic unit of γ-secretase) and the membrane fractions of these cells, the generation of p3-Alc possessing C-terminal γ-cleavage site and Alc ICD possessing N-terminal ε-cleavage site were analysed with MALDI-TOF/MS. We determined the initial ε-site position of all Alcα, Alcβ and Alcγ, and analyzed the relationship between the initially determined ε-site position and the final γ-cleavage position. Conclusions The initial ε-site position does not always determine the final γ-cleavage position in Alcs, which differed from APP. No additional γ-cleavage sites are generated from artificial/non-physiological positions of ε-cleavage for Alcs, while the artificial ε-cleavage positions can influence in selection of physiological γ-site positions. Because alteration of γ-secretase activity is thought to be a pathogenesis of sporadic Alzheimer's disease, Alcs are useful and sensitive substrate to detect the altered cleavage of substrates by γ-secretase, which may be induced by malfunction of γ-secretase itself or changes of membrane environment for enzymatic reaction. PMID:23658629

Transduction of a Foreign Histocompatibility Gene into the Arterial Wall Induces Vasculitis

NASA Astrophysics Data System (ADS)

Nabel, Elizabeth G.; Plautz, Gregory; Nabel, Gary J.

1992-06-01

Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis.

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

PubMed Central

2012-01-01

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. PMID:16964229

Redox-controlled potassium intercalation into two polyaromatic hydrocarbon solids

NASA Astrophysics Data System (ADS)

Romero, F. Denis; Pitcher, M. J.; Hiley, C. I.; Whitehead, G. F. S.; Kar, S.; Ganin, A. Y.; Antypov, D.; Collins, C.; Dyer, M. S.; Klupp, G.; Colman, R. H.; Prassides, K.; Rosseinsky, M. J.

2017-07-01

Alkali metal intercalation into polyaromatic hydrocarbons (PAHs) has been studied intensely after reports of superconductivity in a number of potassium- and rubidium-intercalated materials. There are, however, no reported crystal structures to inform our understanding of the chemistry and physics because of the complex reactivity of PAHs with strong reducing agents at high temperature. Here we present the synthesis of crystalline K2Pentacene and K2Picene by a solid-solid insertion protocol that uses potassium hydride as a redox-controlled reducing agent to access the PAH dianions, and so enables the determination of their crystal structures. In both cases, the inserted cations expand the parent herringbone packings by reorienting the molecular anions to create multiple potassium sites within initially dense molecular layers, and thus interact with the PAH anion π systems. The synthetic and crystal chemistry of alkali metal intercalation into PAHs differs from that into fullerenes and graphite, in which the cation sites are pre-defined by the host structure.

The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture.

PubMed

Pai, Athma A; Henriques, Telmo; McCue, Kayla; Burkholder, Adam; Adelman, Karen; Burge, Christopher B

2017-12-27

Production of most eukaryotic mRNAs requires splicing of introns from pre-mRNA. The splicing reaction requires definition of splice sites, which are initially recognized in either intron-spanning ('intron definition') or exon-spanning ('exon definition') pairs. To understand how exon and intron length and splice site recognition mode impact splicing, we measured splicing rates genome-wide in Drosophila , using metabolic labeling/RNA sequencing and new mathematical models to estimate rates. We found that the modal intron length range of 60-70 nt represents a local maximum of splicing rates, but that much longer exon-defined introns are spliced even faster and more accurately. We observed unexpectedly low variation in splicing rates across introns in the same gene, suggesting the presence of gene-level influences, and we identified multiple gene level variables associated with splicing rate. Together our data suggest that developmental and stress response genes may have preferentially evolved exon definition in order to enhance the rate or accuracy of splicing.

The Meninges: New Therapeutic Targets For Multiple Sclerosis

PubMed Central

Russi, Abigail E.; Brown, Melissa A.

2014-01-01

The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. PMID:25241937

Signatures of Extended Storage of Used Nuclear Fuel in Casks

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

Rauch, Eric Benton

2016-09-28

As the amount of used nuclear fuel continues to grow, more and more used nuclear fuel will be transferred to storage casks. A consolidated storage facility is currently in the planning stages for storing these casks, where at least 10,000 MTHM of fuel will be stored. This site will have potentially thousands of casks once it is operational. A facility this large presents new safeguards and nuclear material accounting concerns. A new signature based on the distribution of neutron sources and multiplication within casks was part of the Department of Energy Office of Nuclear Energy’s Material Protection, Account and Controlmore » Technologies (MPACT) campaign. Under this project we looked at fingerprinting each cask's neutron signature. Each cask has a unique set of fuel, with a unique spread of initial enrichment, burnup, cooling time, and power history. The unique set of fuel creates a unique signature of neutron intensity based on the arrangement of the assemblies. The unique arrangement of neutron sources and multiplication produces a reliable and unique identification of the cask that has been shown to be relatively constant over long time periods. The work presented here could be used to restore from a loss of continuity of knowledge at the storage site. This presentation will show the steps used to simulate and form this signature from the start of the effort through its conclusion in September 2016.« less

The CUG-initiated larger form coat protein of Chinese wheat mosaic virus binds to the cysteine-rich RNA silencing suppressor.

PubMed

Sun, Liying; Andika, Ida Bagus; Shen, Jiangfeng; Yang, Di; Ratti, Claudio; Chen, Jianping

2013-10-01

Some viruses use alternative translation initiation at non-AUG codons as a strategy to produce multiple proteins during gene expression. Here we show that, using this strategy, Chinese wheat mosaic virus (CWMV; Furovirus) expresses a larger form of coat protein (N-ext/CP) in infected plants. Site-directed mutagenesis and transient expression analysis confirmed that CWMV N-ext/CP is initiated at an upstream in-frame CUG codon at nucleotide position 207-209 of RNA 2, which adds a 39 amino acid (aa) N-terminal extension to the major CP. Interestingly, in planta and in vitro analyses indicated that CWMV N-ext/CP but not CP interacts with the CWMV cysteine-rich protein (CRP), an RNA silencing suppressor. We further determined that the N-terminal 39 aa extension, particularly the 10 aa region immediately upstream of the major CP coding region is responsible for the interaction of N-ext/CP with CRP. In an Agrobacterium co-infiltration assay, co-expression with N-ext/CP did not affect CRP silencing suppression activity. Thus the alternative translation initiation at a CUG codon provides the CWMV N-ext/CP with the ability to bind to the viral silencing suppressor. Copyright © 2013 Elsevier B.V. All rights reserved.

Synchronous termination of replication of the two chromosomes is an evolutionary selected feature in Vibrionaceae

PubMed Central

Kemter, Franziska S.; Messerschmidt, Sonja J.; Schallopp, Nadine; Sobetzko, Patrick; Bunk, Boyke; Spröer, Cathrin; Teschler, Jennifer K.; Yildiz, Fitnat H.

2018-01-01

Vibrio cholerae, the causative agent of the cholera disease, is commonly used as a model organism for the study of bacteria with multipartite genomes. Its two chromosomes of different sizes initiate their DNA replication at distinct time points in the cell cycle and terminate in synchrony. In this study, the time-delayed start of Chr2 was verified in a synchronized cell population. This replication pattern suggests two possible regulation mechanisms for other Vibrio species with different sized secondary chromosomes: Either all Chr2 start DNA replication with a fixed delay after Chr1 initiation, or the timepoint at which Chr2 initiates varies such that termination of chromosomal replication occurs in synchrony. We investigated these two models and revealed that the two chromosomes of various Vibrionaceae species terminate in synchrony while Chr2-initiation timing relative to Chr1 is variable. Moreover, the sequence and function of the Chr2-triggering crtS site recently discovered in V. cholerae were found to be conserved, explaining the observed timing mechanism. Our results suggest that it is beneficial for bacterial cells with multiple chromosomes to synchronize their replication termination, potentially to optimize chromosome related processes as dimer resolution or segregation. PMID:29505558

Subunit III-depleted cytochrome c oxidase provides insight into the process of proton uptake by proteins

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan P.

2011-01-01

We review studies of subunit III-depleted cytochrome c oxidase (CcO III (−)) that elucidate the structural basis of steady-state proton uptake from solvent into an internal proton transfer pathway. The removal of subunit III from R. sphaeroides CcO makes proton uptake into the D pathway a rate-determining step, such that measurements of the pH dependence of steady-state O2 consumption can be used to compare the rate and functional pKa of proton uptake by D pathways containing different initial proton acceptors. The removal of subunit III also promotes spontaneous suicide inactivation by CcO, greatly shortening its catalytic lifespan. Because the probability of suicide inactivation is controlled by the rate at which the D pathway delivers protons to the active site, measurements of catalytic lifespan provide a second method to compare the relative efficacy of proton uptake by engineered CcO III (−) forms. These simple experimental systems have been used to explore general questions of proton uptake by proteins, such as the functional value of an initial proton acceptor, whether an initial acceptor must be surface-exposed, which side chains will function as initial proton acceptors and whether multiple acceptors can speed proton uptake. PMID:22023935

Conserved Sequence Preferences Contribute to Substrate Recognition by the Proteasome*

PubMed Central

Yu, Houqing; Singh Gautam, Amit K.; Wilmington, Shameika R.; Wylie, Dennis; Martinez-Fonts, Kirby; Kago, Grace; Warburton, Marie; Chavali, Sreenivas; Inobe, Tomonao; Finkelstein, Ilya J.; Babu, M. Madan

2016-01-01

The proteasome has pronounced preferences for the amino acid sequence of its substrates at the site where it initiates degradation. Here, we report that modulating these sequences can tune the steady-state abundance of proteins over 2 orders of magnitude in cells. This is the same dynamic range as seen for inducing ubiquitination through a classic N-end rule degron. The stability and abundance of His3 constructs dictated by the initiation site affect survival of yeast cells and show that variation in proteasomal initiation can affect fitness. The proteasome's sequence preferences are linked directly to the affinity of the initiation sites to their receptor on the proteasome and are conserved between Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human cells. These findings establish that the sequence composition of unstructured initiation sites influences protein abundance in vivo in an evolutionarily conserved manner and can affect phenotype and fitness. PMID:27226608

Introduction of the American Academy of Facial Plastic and Reconstructive Surgery FACE TO FACE Database.

PubMed

Abraham, Manoj T; Rousso, Joseph J; Hu, Shirley; Brown, Ryan F; Moscatello, Augustine L; Finn, J Charles; Patel, Neha A; Kadakia, Sameep P; Wood-Smith, Donald

2017-07-01

The American Academy of Facial Plastic and Reconstructive Surgery FACE TO FACE database was created to gather and organize patient data primarily from international humanitarian surgical mission trips, as well as local humanitarian initiatives. Similar to cloud-based Electronic Medical Records, this web-based user-generated database allows for more accurate tracking of provider and patient information and outcomes, regardless of site, and is useful when coordinating follow-up care for patients. The database is particularly useful on international mission trips as there are often different surgeons who may provide care to patients on subsequent missions, and patients who may visit more than 1 mission site. Ultimately, by pooling data across multiples sites and over time, the database has the potential to be a useful resource for population-based studies and outcome data analysis. The objective of this paper is to delineate the process involved in creating the AAFPRS FACE TO FACE database, to assess its functional utility, to draw comparisons to electronic medical records systems that are now widely implemented, and to explain the specific benefits and disadvantages of the use of the database as it was implemented on recent international surgical mission trips.

Application of the MIDAS approach for analysis of lysine acetylation sites.

PubMed

Evans, Caroline A; Griffiths, John R; Unwin, Richard D; Whetton, Anthony D; Corfe, Bernard M

2013-01-01

Multiple Reaction Monitoring Initiated Detection and Sequencing (MIDAS™) is a mass spectrometry-based technique for the detection and characterization of specific post-translational modifications (Unwin et al. 4:1134-1144, 2005), for example acetylated lysine residues (Griffiths et al. 18:1423-1428, 2007). The MIDAS™ technique has application for discovery and analysis of acetylation sites. It is a hypothesis-driven approach that requires a priori knowledge of the primary sequence of the target protein and a proteolytic digest of this protein. MIDAS essentially performs a targeted search for the presence of modified, for example acetylated, peptides. The detection is based on the combination of the predicted molecular weight (measured as mass-charge ratio) of the acetylated proteolytic peptide and a diagnostic fragment (product ion of m/z 126.1), which is generated by specific fragmentation of acetylated peptides during collision induced dissociation performed in tandem mass spectrometry (MS) analysis. Sequence information is subsequently obtained which enables acetylation site assignment. The technique of MIDAS was later trademarked by ABSciex for targeted protein analysis where an MRM scan is combined with full MS/MS product ion scan to enable sequence confirmation.

Single CA3 pyramidal cells trigger sharp waves in vitro by exciting interneurones.

PubMed

Bazelot, Michaël; Teleńczuk, Maria T; Miles, Richard

2016-05-15

The CA3 hippocampal region generates sharp waves (SPW), a population activity associated with neuronal representations. The synaptic mechanisms responsible for the generation of these events still require clarification. Using slices maintained in an interface chamber, we found that the firing of single CA3 pyramidal cells triggers SPW like events at short latencies, similar to those for the induction of firing in interneurons. Multi-electrode records from the CA3 stratum pyramidale showed that pyramidal cells triggered events consisting of putative interneuron spikes followed by field IPSPs. SPW fields consisted of a repetition of these events at intervals of 4-8 ms. Although many properties of induced and spontaneous SPWs were similar, the triggered events tended to be initiated close to the stimulated cell. These data show that the initiation of SPWs in vitro is mediated via pyramidal cell synapses that excite interneurons. They do not indicate why interneuron firing is repeated during a SPW. Sharp waves (SPWs) are a hippocampal population activity that has been linked to neuronal representations. We show that SPWs in the CA3 region of rat hippocampal slices can be triggered by the firing of single pyramidal cells. Single action potentials in almost one-third of pyramidal cells initiated SPWs at latencies of 2-5 ms with probabilities of 0.07-0.76. Initiating pyramidal cells evoked field IPSPs (fIPSPs) at similar latencies when SPWs were not initiated. Similar spatial profiles for fIPSPs and middle components of SPWs suggested that SPW fields reflect repeated fIPSPs. Multiple extracellular records showed that the initiated SPWs tended to start near the stimulated pyramidal cell, whereas spontaneous SPWs could emerge at multiple sites. Single pyramidal cells could initiate two to six field IPSPs with distinct amplitude distributions, typically preceeded by a short-duration extracellular action potential. Comparison of these initiated fields with spontaneously occurring inhibitory field motifs allowed us to identify firing in different interneurones during the spread of SPWs. Propagation away from an initiating pyramidal cell was typically associated with the recruitment of interneurones and field IPSPs that were not activated by the stimulated pyramidal cell. SPW fields initiated by single cells were less variable than spontaneous events, suggesting that more stereotyped neuronal ensembles were activated, although neither the spatial profiles of fields, nor the identities of interneurone firing were identical for initiated events. The effects of single pyramidal cell on network events are thus mediated by different sequences of interneurone firing. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Darwin Assembly: fast, efficient, multi-site bespoke mutagenesis

PubMed Central

Cozens, Christopher

2018-01-01

Abstract Engineering proteins for designer functions and biotechnological applications almost invariably requires (or at least benefits from) multiple mutations to non-contiguous residues. Several methods for multiple site-directed mutagenesis exist, but there remains a need for fast and simple methods to efficiently introduce such mutations – particularly for generating large, high quality libraries for directed evolution. Here, we present Darwin Assembly, which can deliver high quality libraries of >108 transformants, targeting multiple (>10) distal sites with minimal wild-type contamination (<0.25% of total population) and which takes a single working day from purified plasmid to library transformation. We demonstrate its efficacy with whole gene codon reassignment of chloramphenicol acetyl transferase, mutating 19 codons in a single reaction in KOD DNA polymerase and generating high quality, multiple-site libraries in T7 RNA polymerase and Tgo DNA polymerase. Darwin Assembly uses commercially available enzymes, can be readily automated, and offers a cost-effective route to highly complex and customizable library generation. PMID:29409059

Origin of Multiple Peaks in the Potentiodynamic Oxidation of CO Adlayers on Pt and Ru-Modified Pt Electrodes

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

Wang, Hongsen; Abruña, Héctor D.

2015-05-21

The study of the electrooxidation mechanism of COad on Pt based catalysts is very important for designing more effective CO-tolerant electrocatalysts for fuel cells. We have studied the origin of multiple peaks in the cyclic voltammograms of CO stripping from polycrystalline Pt and Ru modified polycrystalline Pt (Pt/Ru) surfaces in both acidic and alkaline media by differential electrochemical mass spectrometry (DEMS), DFT calculations, and kinetic Monte Carlo (KMC) simulations. A new COad electrooxidation kinetic model on heterogeneous Pt and Pt/Ru catalysts is proposed to account for the multiple peaks experimentally observed. In this model, OH species prefer to adsorb atmore » low-coordination sites or Ru sites and, thus, suppress CO repopulation from high-coordination sites onto these sites. Therefore, COad oxidation occurs on different facets or regions, leading to multiplicity of CO stripping peaks. This work provides a new insight into the CO electrooxidation mechanism and kinetics on heterogeneous catalysts.« less

HIV integration sites in latently infected cell lines: evidence of ongoing replication.

PubMed

Symons, Jori; Chopra, Abha; Malatinkova, Eva; De Spiegelaere, Ward; Leary, Shay; Cooper, Don; Abana, Chike O; Rhodes, Ajantha; Rezaei, Simin D; Vandekerckhove, Linos; Mallal, Simon; Lewin, Sharon R; Cameron, Paul U

2017-01-13

Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines. Latently infected cell lines infected with intact virus demonstrated multiple distinct HIV integration sites (28 different sites in U1, 110 in ACH-2 and 117 in J1.1 per 150,000 cells). In contrast, cell lines infected with replication-incompetent viruses (J-Lat cells) demonstrated single integration sites. Following in vitro passaging of the ACH-2 cell line, we observed a significant increase in the frequency of unique HIV integration sites and there were multiple mutations and large deletions in the proviral DNA. When the ACH-2 cell line was cultured with the integrase inhibitor raltegravir, there was a significant decrease in the number of unique HIV integration sites and a transient increase in the frequency of 2-LTR circles consistent with virus replication in these cells. Cell lines latently infected with intact HIV demonstrated multiple unique HIV integration sites indicating that these cell lines are not clonal and in the ACH-2 cell line there was evidence of low level virus replication. These findings have implications for the use of latently infected cell lines as models of HIV latency and for the use of these cells as standards.

Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli.

PubMed Central

Liu, J; Turnbough, C L

1994-01-01

In Escherichia coli, expression of the pyrC gene is regulated primarily by a translational control mechanism based on nucleotide-sensitive selection of transcriptional start sites at the pyrC promoter. When intracellular levels of CTP are high, pyrC transcripts are initiated predominantly with CTP at a site 7 bases downstream of the Pribnow box. These transcripts form a stable hairpin at their 5' ends that blocks ribosome binding. When the CTP level is low and the GTP level is high, conditions found in pyrimidine-limited cells, transcripts are initiated primarily with GTP at a site 9 bases downstream of the Pribnow box. These shorter transcripts are unable to form a hairpin at their 5' ends and are readily translated. In this study, we examined the effects of nucleotide sequence and position on the selection of transcriptional start sites at the pyrC promoter. We characterized promoter mutations that systematically alter the sequence at position 7 or 9 downstream of the Pribnow box or vary the spacing between the Pribnow box and wild-type transcriptional initiation region. The results reveal preferences for particular initiating nucleotides (ATP > or = GTP > UTP >> CTP) and for starting positions downstream of the Pribnow box (7 >> 6 and 8 > 9 > 10). The results indicate that optimal nucleotide-sensitive start site switching at the wild-type pyrC promoter is the result of competition between the preferred start site (position 7) that uses the poorest initiating nucleotide (CTP) and a weak start site (position 9) that uses a good initiating nucleotide (GTP). The sequence of the pyrC promoter also minimizes the synthesis of untranslatable transcripts and provides for maximum stability of the regulatory transcript hairpin. In addition, the results show that the effects of the mutations on pyrC expression and regulation are consistent with the current model for translational control. Possible effects of preferences for initiating nucleotides and start sites on the expression and regulation of other genes are discussed. Images PMID:7910603

A comparative study of rhodopsin function in the great bowerbird (Ptilonorhynchus nuchalis): Spectral tuning and light-activated kinetics.

PubMed

van Hazel, Ilke; Dungan, Sarah Z; Hauser, Frances E; Morrow, James M; Endler, John A; Chang, Belinda S W

2016-07-01

Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well-characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein-coupled receptors. While this substitution is present in some dim-light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site-directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue-shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light-activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure-function as well as their evolutionary significance for dim-light vision across vertebrates. © 2016 The Protein Society.

Importance of initial and final state effects for azimuthal correlations in p + Pb collisions

DOE PAGES

Greif, Moritz; Greiner, Carsten; Schenke, Bjorn; ...

2017-11-27

In this work, we investigate the relative importance of initial and final state effects on azimuthal correlations of gluons in low and high multiplicity p+Pb collisions. To achieve this, we couple Yang-Mills dynamics of pre-equilibrium gluon fields (IP-GLASMA) to a perturbative QCD based parton cascade for the final state evolution (BAMPS) on an event-by-event basis. We find that signatures of both the initial state correlations and final state interactions are seen in azimuthal correlation observables, such as v 2 {2PC} (p T), their strength depending on the event multiplicity and transverse momentum. Initial state correlations dominate v 2 {2PC} (pmore » T) in low multiplicity events for transverse momenta p T > 2 GeV. Lastly, while final state interactions are dominant in high multiplicity events, initial state correlations affect v 2 {2PC} (p T) for p T > 2 GeV as well as the pT integrated v 2 {2PC}.« less

Importance of initial and final state effects for azimuthal correlations in p + Pb collisions

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

Greif, Moritz; Greiner, Carsten; Schenke, Bjorn

In this work, we investigate the relative importance of initial and final state effects on azimuthal correlations of gluons in low and high multiplicity p+Pb collisions. To achieve this, we couple Yang-Mills dynamics of pre-equilibrium gluon fields (IP-GLASMA) to a perturbative QCD based parton cascade for the final state evolution (BAMPS) on an event-by-event basis. We find that signatures of both the initial state correlations and final state interactions are seen in azimuthal correlation observables, such as v 2 {2PC} (p T), their strength depending on the event multiplicity and transverse momentum. Initial state correlations dominate v 2 {2PC} (pmore » T) in low multiplicity events for transverse momenta p T > 2 GeV. Lastly, while final state interactions are dominant in high multiplicity events, initial state correlations affect v 2 {2PC} (p T) for p T > 2 GeV as well as the pT integrated v 2 {2PC}.« less

A Bayesian belief network approach for assessing uncertainty in conceptual site models at contaminated sites

NASA Astrophysics Data System (ADS)

Thomsen, Nanna I.; Binning, Philip J.; McKnight, Ursula S.; Tuxen, Nina; Bjerg, Poul L.; Troldborg, Mads

2016-05-01

A key component in risk assessment of contaminated sites is in the formulation of a conceptual site model (CSM). A CSM is a simplified representation of reality and forms the basis for the mathematical modeling of contaminant fate and transport at the site. The CSM should therefore identify the most important site-specific features and processes that may affect the contaminant transport behavior at the site. However, the development of a CSM will always be associated with uncertainties due to limited data and lack of understanding of the site conditions. CSM uncertainty is often found to be a major source of model error and it should therefore be accounted for when evaluating uncertainties in risk assessments. We present a Bayesian belief network (BBN) approach for constructing CSMs and assessing their uncertainty at contaminated sites. BBNs are graphical probabilistic models that are effective for integrating quantitative and qualitative information, and thus can strengthen decisions when empirical data are lacking. The proposed BBN approach facilitates a systematic construction of multiple CSMs, and then determines the belief in each CSM using a variety of data types and/or expert opinion at different knowledge levels. The developed BBNs combine data from desktop studies and initial site investigations with expert opinion to assess which of the CSMs are more likely to reflect the actual site conditions. The method is demonstrated on a Danish field site, contaminated with chlorinated ethenes. Four different CSMs are developed by combining two contaminant source zone interpretations (presence or absence of a separate phase contamination) and two geological interpretations (fractured or unfractured clay till). The beliefs in each of the CSMs are assessed sequentially based on data from three investigation stages (a screening investigation, a more detailed investigation, and an expert consultation) to demonstrate that the belief can be updated as more information becomes available.

Outdoor Education - A Guide to Site Planning and Implementation of Programs.

ERIC Educational Resources Information Center

Texas Education Agency, Austin. Div. of Curriculum Development.

This booklet presents guidelines for initiating outdoor instructional programs. Initially, the guide lists the objectives of outdoor education: survival, recreation, development of personal health and well-being, career opportunities, and social adjustment. A discussion follows on the three phases of site planning. The first phase is site analysis…

Use of model organism and disease databases to support matchmaking for human disease gene discovery.

PubMed

Mungall, Christopher J; Washington, Nicole L; Nguyen-Xuan, Jeremy; Condit, Christopher; Smedley, Damian; Köhler, Sebastian; Groza, Tudor; Shefchek, Kent; Hochheiser, Harry; Robinson, Peter N; Lewis, Suzanna E; Haendel, Melissa A

2015-10-01

The Matchmaker Exchange application programming interface (API) allows searching a patient's genotypic or phenotypic profiles across clinical sites, for the purposes of cohort discovery and variant disease causal validation. This API can be used not only to search for matching patients, but also to match against public disease and model organism data. This public disease data enable matching known diseases and variant-phenotype associations using phenotype semantic similarity algorithms developed by the Monarch Initiative. The model data can provide additional evidence to aid diagnosis, suggest relevant models for disease mechanism and treatment exploration, and identify collaborators across the translational divide. The Monarch Initiative provides an implementation of this API for searching multiple integrated sources of data that contextualize the knowledge about any given patient or patient family into the greater biomedical knowledge landscape. While this corpus of data can aid diagnosis, it is also the beginning of research to improve understanding of rare human diseases. © 2015 WILEY PERIODICALS, INC.

Low cycle fatigue behavior of a ferritic reactor pressure vessel steel

NASA Astrophysics Data System (ADS)

Sarkar, Apu; Kumawat, Bhupendra K.; Chakravartty, J. K.

2015-07-01

The cyclic stress-strain response and the low cycle fatigue (LCF) behavior of 20MnMoNi55 pressure vessel steel were studied. Tensile strength and LCF properties were examined at room temperature (RT) using specimens cut from rolling direction of a rolled block. The fully reversed strain-controlled LCF tests were conducted at a constant total strain rate with different axial strain amplitude levels. The cyclic strain-stress relationships and the strain-life relationships were obtained through the test results, and related LCF parameters of the steel were calculated. The studied steel exhibits cyclic softening behavior. Furthermore, analysis of stabilized hysteresis loops showed that the steel exhibits non-Masing behavior. Complementary scanning electron microscopy examinations were also carried out on fracture surfaces to reveal dominant damage mechanisms during crack initiation, propagation and fracture. Multiple crack initiation sites were observed on the fracture surface. The investigated LCF behavior can provide reference for pressure vessel life assessment and fracture mechanisms analysis.

Retention in Differentiated Care: Multiple Measures Analysis for a Decentralized HIV Care and Treatment Program in North Central Nigeria

PubMed Central

Agaba, Patricia A; Genberg, Becky L; Sagay, Atiene S; Agbaji, Oche O; Meloni, Seema T; Dadem, Nancin Y; Kolawole, Grace O; Okonkwo, Prosper; Kanki, Phyllis J; Ware, Norma C

2018-01-01

Objective Differentiated care refers collectively to flexible service models designed to meet the differing needs of HIV-infected persons in resource-scarce settings. Decentralization is one such service model. Retention is a key indicator for monitoring the success of HIV treatment and care programs. We used multiple measures to compare retention in a cohort of patients receiving HIV care at “hub” (central) and “spoke” (decentralized) sites in a large public HIV treatment program in north central Nigeria. Methods This retrospective cohort study utilized longitudinal program data representing central and decentralized levels of care in the Plateau State Decentralization Initiative, north central Nigeria. We examined retention with patient- level (retention at fixed times, loss-to-follow-up [LTFU]) and visit-level (gaps-in-care, visit constancy) measures. Regression models with generalized estimating equations (GEE) were used to estimate the effect of decentralization on visit-level measures. Patient-level measures were examined using survival methods with Cox regression models, controlling for baseline variables. Results Of 15,650 patients, 43% were enrolled at the hub. Median time in care was 3.1 years. Hub patients were less likely to be LTFU (adjusted hazard ratio (AHR)=0.91, 95% CI: 0.85-0.97), compared to spoke patients. Visit constancy was lower at the hub (−4.5%, 95% CI: −3.5, −5.5), where gaps in care were also more likely to occur (adjusted odds ratio=1.95, 95% CI: 1.83-2.08). Conclusion Decentralized sites demonstrated better retention outcomes using visit-level measures, while the hub achieved better retention outcomes using patient-level measures. Retention estimates produced by incorporating multiple measures showed substantial variation, confirming the influence of measurement strategies on the results of retention research. Future studies of retention in HIV care in sub-Saharan Africa will be well-served by including multiple measures. PMID:29682399

Retention in Differentiated Care: Multiple Measures Analysis for a Decentralized HIV Care and Treatment Program in North Central Nigeria.

PubMed

Agaba, Patricia A; Genberg, Becky L; Sagay, Atiene S; Agbaji, Oche O; Meloni, Seema T; Dadem, Nancin Y; Kolawole, Grace O; Okonkwo, Prosper; Kanki, Phyllis J; Ware, Norma C

2018-01-01

Differentiated care refers collectively to flexible service models designed to meet the differing needs of HIV-infected persons in resource-scarce settings. Decentralization is one such service model. Retention is a key indicator for monitoring the success of HIV treatment and care programs. We used multiple measures to compare retention in a cohort of patients receiving HIV care at "hub" (central) and "spoke" (decentralized) sites in a large public HIV treatment program in north central Nigeria. This retrospective cohort study utilized longitudinal program data representing central and decentralized levels of care in the Plateau State Decentralization Initiative, north central Nigeria. We examined retention with patient- level (retention at fixed times, loss-to-follow-up [LTFU]) and visit-level (gaps-in-care, visit constancy) measures. Regression models with generalized estimating equations (GEE) were used to estimate the effect of decentralization on visit-level measures. Patient-level measures were examined using survival methods with Cox regression models, controlling for baseline variables. Of 15,650 patients, 43% were enrolled at the hub. Median time in care was 3.1 years. Hub patients were less likely to be LTFU (adjusted hazard ratio (AHR)=0.91, 95% CI: 0.85-0.97), compared to spoke patients. Visit constancy was lower at the hub (-4.5%, 95% CI: -3.5, -5.5), where gaps in care were also more likely to occur (adjusted odds ratio=1.95, 95% CI: 1.83-2.08). Decentralized sites demonstrated better retention outcomes using visit-level measures, while the hub achieved better retention outcomes using patient-level measures. Retention estimates produced by incorporating multiple measures showed substantial variation, confirming the influence of measurement strategies on the results of retention research. Future studies of retention in HIV care in sub-Saharan Africa will be well-served by including multiple measures.

Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex

PubMed Central

Liu, Jun; McConnell, Kristopher; Dixon, Michael; Calvi, Brian R.

2012-01-01

Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID:22049023

24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Any development will likely have some impact on the surrounding environment. Development which... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Regulatory exemption-multiple site subdivision-determination required. 1710.15 Section 1710.15 Housing and Urban Development Regulations Relating...

24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Any development will likely have some impact on the surrounding environment. Development which... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Regulatory exemption-multiple site subdivision-determination required. 1710.15 Section 1710.15 Housing and Urban Development Regulations Relating...

24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Any development will likely have some impact on the surrounding environment. Development which... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Regulatory exemption-multiple site subdivision-determination required. 1710.15 Section 1710.15 Housing and Urban Development Regulations Relating...

24 CFR 1710.15 - Regulatory exemption-multiple site subdivision-determination required.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Any development will likely have some impact on the surrounding environment. Development which... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Regulatory exemption-multiple site subdivision-determination required. 1710.15 Section 1710.15 Housing and Urban Development Regulations Relating...

Impact of extended prostate biopsy including apical anterior region for cancer detection and prediction of surgical margin status for radical prostatectomy.

PubMed

Hashimoto, Kohei; Shinkai, Nobuo; Tanaka, Toshiaki; Masumori, Naoya

2017-06-01

We investigated diagnostic yield of initial biopsy and repeated biopsy including apical cores. We investigated 573 consecutive men with PSA of ≤20 ng/ml who underwent prostate biopsy between 2004 and 2013. The initial 14-core biopsy consisted of the sextant type, lateral sites at the base and middle, lateral apices (la) at anterior horn sites, and apical anterior sites (aa). The repeated 18-core biopsy consisted of the initial 14-core biopsy with four transition zone (TZ) sites at the base (tzb) and middle (tzm). Prostate cancer was diagnosed in 178 (38.9%) of 458 men with the initial 14-core biopsy, and 44 (38.3%) of 115 men with the repeated 18-core biopsy. In the initial biopsy setting, the unique cancer detection rate was high in apical sites (apex, la, and aa: 6.2%, 6.2% and 5.1%, respectively). In the repeated setting, it was high in the TZ site in addition to the apical site (apex, la, aa, tzm, and tzb: 6.8%, 6.8%, 11.4%, 9.1% and 11.4%, respectively). The positive SM rate at the apex was higher in patients whose cancer was detected only in sites other than the sextant region than for those in the sextant region (36.4% vs. 14.8%, P = 0.037). The initial 14-core and the repeated 18-core biopsy scheme including apical anterior cores are feasible for prostate cancer detection. We propose that apical biopsy cores can be used to predict not only the existence of cancer but also surgical margin status at the apex. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Consequences of germline variation disrupting the constitutional translational initiation codon start sites of MLH1 and BRCA2: use of potential alternative start sites and implications for predicting variant pathogenicity

PubMed Central

Parsons, Michael T.; Whiley, Phillip J.; Beesley, Jonathan; Drost, Mark; de Wind, Niels; Thompson, Bryony A.; Marquart, Louise; Hopper, John L.; Jenkins, Mark A.; Brown, Melissa A.; Tucker, Kathy; Warwick, Linda; Buchanan, Daniel D.; Spurdle, Amanda B.

2014-01-01

Variants that disrupt the translation initiation sequences in cancer predisposition genes are generally assumed to be deleterious. However few studies have validated these assumptions with functional and clinical data. Two cancer syndrome gene variants likely to affect native translation initiation were identified by clinical genetic testing: MLH1:c.1A>G p.(Met1?) and BRCA2:c.67+3A>G. In vitro GFP-reporter assays were conducted to assess the consequences of translation initiation disruption on alternative downstream initiation codon usage. Analysis of MLH1:c.1A>G p.(Met1?) showed that translation was mostly initiated at an in-frame position 103 nucleotides downstream, but also at two ATG sequences downstream. The protein product encoded by the in-frame transcript initiating from position c.103 showed loss of in vitro mismatch repair activity comparable to known pathogenic mutations. BRCA2:c.67+3A>G was shown by mRNA analysis to result in an aberrantly spliced transcript deleting exon 2 and the consensus ATG site. In the absence of exon 2, translation initiated mostly at an out-of-frame ATG 323 nucleotides downstream, and to a lesser extent at an in-frame ATG 370 nucleotides downstream. Initiation from any of the downstream alternative sites tested in both genes would lead to loss of protein function, but further clinical data is required to confirm if these variants are associated with a high cancer risk. Importantly, our results highlight the need for caution in interpreting the functional and clinical consequences of variation that leads to disruption of the initiation codon, since translation may not necessarily occur from the first downstream alternative start site, or from a single alternative start site. PMID:24302565

PreTIS: A Tool to Predict Non-canonical 5’ UTR Translational Initiation Sites in Human and Mouse

PubMed Central

Reuter, Kerstin; Helms, Volkhard

2016-01-01

Translation of mRNA sequences into proteins typically starts at an AUG triplet. In rare cases, translation may also start at alternative non–AUG codons located in the annotated 5’ UTR which leads to an increased regulatory complexity. Since ribosome profiling detects translational start sites at the nucleotide level, the properties of these start sites can then be used for the statistical evaluation of functional open reading frames. We developed a linear regression approach to predict in–frame and out–of–frame translational start sites within the 5’ UTR from mRNA sequence information together with their translation initiation confidence. Predicted start codons comprise AUG as well as near–cognate codons. The underlying datasets are based on published translational start sites for human HEK293 and mouse embryonic stem cells that were derived by the original authors from ribosome profiling data. The average prediction accuracy of true vs. false start sites for HEK293 cells was 80%. When applied to mouse mRNA sequences, the same model predicted translation initiation sites observed in mouse ES cells with an accuracy of 76%. Moreover, we illustrate the effect of in silico mutations in the flanking sequence context of a start site on the predicted initiation confidence. Our new webservice PreTIS visualizes alternative start sites and their respective ORFs and predicts their ability to initiate translation. Solely, the mRNA sequence is required as input. PreTIS is accessible at http://service.bioinformatik.uni-saarland.de/pretis. PMID:27768687

Structural Protein 4.1 in the Nucleus of Human Cells: Dynamic Rearrangements during Cell Division

PubMed Central

Krauss, Sharon Wald; Larabell, Carolyn A.; Lockett, Stephen; Gascard, Philippe; Penman, Sheldon; Mohandas, Narla; Chasis, Joel Anne

1997-01-01

Structural protein 4.1, first identified as a crucial 80-kD protein in the mature red cell membrane skeleton, is now known to be a diverse family of protein isoforms generated by complex alternative mRNA splicing, variable usage of translation initiation sites, and posttranslational modification. Protein 4.1 epitopes are detected at multiple intracellular sites in nucleated mammalian cells. We report here investigations of protein 4.1 in the nucleus. Reconstructions of optical sections of human diploid fibroblast nuclei using antibodies specific for 80-kD red cell 4.1 and for 4.1 peptides showed 4.1 immunofluorescent signals were intranuclear and distributed throughout the volume of the nucleus. After sequential extractions of cells in situ, 4.1 epitopes were detected in nuclear matrix both by immunofluorescence light microscopy and resinless section immunoelectron microscopy. Western blot analysis of fibroblast nuclear matrix protein fractions, isolated under identical extraction conditions as those for microscopy, revealed several polypeptide bands reactive to multiple 4.1 antibodies against different domains. Epitope-tagged protein 4.1 was detected in fibroblast nuclei after transient transfections using a construct encoding red cell 80-kD 4.1 fused to an epitope tag. Endogenous protein 4.1 epitopes were detected throughout the cell cycle but underwent dynamic spatial rearrangements during cell division. Protein 4.1 was observed in nucleoplasm and centrosomes at interphase, in the mitotic spindle during mitosis, in perichromatin during telophase, as well as in the midbody during cytokinesis. These results suggest that multiple protein 4.1 isoforms may contribute significantly to nuclear architecture and ultimately to nuclear function. PMID:9128242

Increasing bone sclerosis during bortezomib therapy in multiple myeloma patients: results of a reduced-dose whole-body MDCT study.

PubMed

Schulze, Maximilian; Weisel, Katja; Grandjean, Caroline; Oehrlein, Katharina; Zago, Manola; Spira, Daniel; Horger, Marius

2014-01-01

The objective of our study was to assess the frequency, location, extent, and patterns of bone sclerosis occurring in patients with multiple myeloma (MM) during bortezomib-based therapy. From June 2003 through December 2011, 593 whole-body reduced-dose MDCT studies were performed of 79 consecutive patients receiving bortezomib. The median surveillance time was 21 months (range, 3-67 months). Baseline studies were compared with follow-up studies during therapy (follow-up 1), at the end of therapy (follow-up 2), and 12 months after cessation of bortezomib therapy (follow-up 3). We recorded any sclerotic change occurring inside or along the margins of the osteolytic lesions, in the cancellous bone, or inside preexistent medullary or extramedullary lesions. The time point of occurrence of bone sclerosis was correlated with the best hematologic response category. Fourteen (17.7%) patients developed focal (n = 11) or diffuse (n = 3) bone sclerosis. The time window from bortezomib initiation to radiographic detection of bone sclerosis was 8 months (SD, 7 months). Sclerosis occurred at multiple sites (n = 7) or at an isolated site (n = 7). On subsequent whole-body reduced-dose MDCT studies, sclerosis further increased in seven (50%) patients. Hematologic best response during bortezomib treatment was complete response (n = 1), very good partial response (n = 2), partial response (n = 8), and stable disease (n = 3). Radiologic response at the time of sclerosis detection was partial response (n = 8), stable disease (n = 2), and progressive disease (n = 4). Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.

Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site.

PubMed

Letessier, Anne; Millot, Gaël A; Koundrioukoff, Stéphane; Lachagès, Anne-Marie; Vogt, Nicolas; Hansen, R Scott; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle

2011-02-03

Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks. Here we show, in contrast to this view, that the fragility of FRA3B--the most active common fragile site in human lymphocytes--does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting and replication timing are highly plastic in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes. Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.

Application of a topical vapocoolant spray decreases pain at the site of initial intradermal anaesthetic injection during ultrasound-guided breast needle biopsy.

PubMed

Collado-Mesa, F; Net, J M; Arheart, K; Klevos, G A; Yepes, M M

2015-09-01

To assess whether the application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy decreases pain at the site of the initial injection. In this institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study, 50 women aged 49.1 ± 1.6 years (mean ± standard error) were recruited and provided written informed consent. Participants served as their own controls and were blinded as to whether a topical vapocoolant spray or a placebo was used immediately prior to the initial local anaesthetic injection at two separate biopsy sites. With the exception of the application of vapocoolant or placebo, the entire ultrasound-guided procedure was performed according to a routine protocol. Participants recorded pain at initial injection site on a visual analogue scale. General linear mixed models for repeated measures analysis of variance and a 0.05 significance level were used. Application of topical vapocoolant spray was shown to significantly decrease pain at the site of initial intradermal anaesthetic injection as compared to placebo (p<0.001). Treatment effect was independent of age of the subject, race/ethnicity, operator, type of biopsy device, and histopathology result. No complications from vapocoolant spray use were reported. Application of a topical vapocoolant spray immediately prior to initial intradermal anaesthetic injection during ultrasound-guided breast biopsy significantly decreases pain at the site of the initial injection and could contribute to improve the patient's overall procedural experience. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice.

PubMed

Liu, Chengwen; Lou, Yanyan; Lizée, Gregory; Qin, Hong; Liu, Shujuan; Rabinovich, Brian; Kim, Grace J; Wang, Yi-Hong; Ye, Yang; Sikora, Andrew G; Overwijk, Willem W; Liu, Yong-Jun; Wang, Gang; Hwu, Patrick

2008-03-01

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-gamma production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells.

The Role of Outdoor Art in Urban Environmental Education

NASA Astrophysics Data System (ADS)

Filippelli, G. M.; Kesling, M.; Ryan, T.; Fraser, J.; McDonald, F.; Rollings, A.; Miss, M.; Kanpetch, B.; Trueblood, M.

2015-12-01

Finding ways to engage youth in inadvertent learning about nature and the environment is challenging, particularly in urban areas where environmental literacy is profoundly limited by access to safe and representative spaces. Termed the Nature Deficit Disorder, the lack of contact and connection between people and their environment leads to a less than holistic approach to environmental management at the personal and governmental levels. One of the challenges is developing ways to engage youth in science learning not by bringing them indoors to a science museum but rather by taking the science museum outdoors. Funded by the NSF Informal Science Learning program, we launched a collaborative between scientists and artists to understand the nature and impact of environmental learning through outdoor art and science programming, called StreamLines. Launched in 2014 and now near full deployment, the program is part of a bigger initiative in Indianapolis (Reconnecting to Our Waterways) to embrace the multiple waterways that traverse the city as a valuable community and health resource. This collaborative is designed to function on multiple levels. An Artist and Scientists Roundtable engages practitioners in regular conversations supplemented by external readings to share how practitioners use concepts and tools from the "opposite" side to inform their work and scholarship. Physical installations of iconic art at individual sites reflect the environmental conditions at individual sites are designed as tools for explicit and implicit learning and exploration about the environment. Music, poetry, and dance programming developed for individual sites portray cogent characteristics of place and are meant to allow visitors to see how artists engage with and draw from the environment for inspiration. A research approach unpins all of these efforts, utilizing a set of different sample populations to explore environmental education and potential advocacy after interactions with components of StreamLines.

Variation in Responses of Fishes across Multiple Reserves within a Network of Marine Protected Areas in Temperate Waters

PubMed Central

Starr, Richard M.; Wendt, Dean E.; Barnes, Cheryl L.; Marks, Corina I.; Malone, Dan; Waltz, Grant; Schmidt, Katherine T.; Chiu, Jennifer; Launer, Andrea L.; Hall, Nathan C.; Yochum, Noëlle

2015-01-01

Meta-analyses of field studies have shown that biomass, density, species richness, and size of organisms protected by no-take marine reserves generally increase over time. The magnitude and timing of changes in these response variables, however, vary greatly and depend upon the taxonomic groups protected, size and type of reserve, oceanographic regime, and time since the reserve was implemented. We conducted collaborative, fishery-independent surveys of fishes for seven years in and near newly created marine protected areas (MPAs) in central California, USA. Results showed that initially most MPAs contained more and larger fishes than associated reference sites, likely due to differences in habitat quality. The differences between MPAs and reference sites did not greatly change over the seven years of our study, indicating that reserve benefits will be slow to accumulate in California’s temperate eastern boundary current. Fishes in an older reserve that has been closed to fishing since 1973, however, were significantly more abundant and larger than those in associated reference sites. This indicates that reserve benefits are likely to accrue in the California Current ecosystem, but that 20 years or more may be needed to detect significant changes in response variables that are due to MPA implementation. Because of the high spatial and temporal variability of fish recruitment patterns, long-term monitoring is needed to identify positive responses of fishes to protection in the diverse set of habitats in a dynamic eastern boundary current. Qualitative estimates of response variables, such as would be obtained from an expert opinion process, are unlikely to provide an accurate description of MPA performance. Similarly, using one species or one MPA as an indicator is unlikely to provide sufficient resolution to accurately describe the performance of multiple MPAs. PMID:25760856

Multiple Nonspecific Sites of Joint Pain Outside the Knees Develop in Persons With Knee Pain.

PubMed

Felson, David T; Niu, Jingbo; Quinn, Emily K; Neogi, Tuhina; Lewis, Cara L; Lewis, Cora E; Frey Law, Laura; McCulloch, Chuck; Nevitt, Michael; LaValley, Michael

2017-02-01

Many persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized. We studied persons ages 50-79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5-7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain. In the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded. Persons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern. © 2016, American College of Rheumatology.

Multifocal pigmented villonodular synovitis in a child. A case report.

PubMed

Kay, R M; Eckardt, J J; Mirra, J M

1996-01-01

Pigmented villonodular synovitis is a well-described disease that almost universally involves a single site. This is a report of an unusual case of multiple site involvement of pigmented villonodular synovitis in a child. In addition to multiple site involvement, the case is unusual for several reasons: asymmetric involvement, involvement of both upper and lower extremities, involvement of the pes anserine tendons, and the patient is an otherwise healthy child.

Effectiveness of Shot Peening in Suppressing Fatigue Cracking at Non-Metallic Inclusions in Udimet(trademark) 720

NASA Technical Reports Server (NTRS)

Barrie, Robert L.; Gabb, Timothy P.; Telesman, Jack; Kantzos, Peter T.; Prescenzi, Anthony; Biles, Tiffany; Bonacuse, Peter J.

2005-01-01

The fatigue lives of modern powder metallurgy disk alloys can be reduced by over an order of magnitude by surface cracking at inherent non-metallic inclusions. The objective of this work was to study the effectiveness of shot peening in suppressing LCF crack initiation and growth at surface nonmetallic inclusions. Inclusions were carefully introduced at elevated levels during powder metallurgy processing of the nickel-base disk superalloy Udimet 720. Multiple strain-controlled fatigue tests were then performed on machined specimens at 427 and 650 C in peened and unpeened conditions. Analyses were performed to compare the low cycle fatigue lives and failure initiation sites as a function of inclusion content, shot peening, and fatigue conditions. A large majority of the failures in as-machined specimens with introduced inclusions occurred at cracks initiating from inclusions intersecting the specimen surface. The inclusions could reduce fatigue life by up to 100X. Large inclusions had the greatest effect on life in tests at low strain ranges and high strain ratios. Shot peening can be used to improve life in these conditions by reducing the most severe effects of inclusions.

DIY guide-needle-assisted conjunctivodacryocystorhinostomy (CDCR).

PubMed

Paik, Ji-Sun; Kim, Su-Ah; Doh, Sang-Hee

2013-01-01

In this study, we introduce DIY guide-needle-assisted conjunctivodacryocystorhinostomy (CDCR), in which a guide needle helps in measuring the initial Jones tube length for insertion and reduces unnecessary handling for tube changes. Three CDCR procedures were conducted in which the length of the Jones tube was calculated using a 22-gauge DIY guide needle, and a prospective study of tube position change and migration, (a major cause of CDCR failure) was done. Wound healing was almost complete within 4 weeks postoperatively in the osteotomy site, but in cases of partial middle turbinectomy, a little more time was necessary. There was a slight change in Jones tube position in the nasal cavity compared with the expected position of original tube tip, but no tube migration from the caruncle fixation position had occurred by the final follow-up time. This guide-needle-assisted CDCR has multiple advantages, such as easy measurement of the proper initial tube size, utilization of the initial needle path, and easy replacement of tubes. Finally, this approach to CDCR can be readily applied because it uses materials ordinarily found in hospitals to create the devices needed for the procedure, so there is no additional cost.

Effectiveness of Shot Peening In Suppressing Fatigue Cracking At Non-Metallic Inclusions In Udimet(Registered Trademark)720

NASA Technical Reports Server (NTRS)

Barrie, Robert L.; Gabb, Timothy P.; Telesman, Jack; Kantzos, Peter T.; Prescenzi, Anthony; Biles, T.; Bonacuse, P. J.

2006-01-01

The fatigue lives of modern powder metallurgy disk alloys can be reduced over an order of magnitude by cracking at inherent non-metallic inclusions. The objective of this work was to study the effectiveness of shot peening in suppressing LCF crack initiation and growth at surface nonmetallic inclusions. Inclusions were carefully introduced at elevated levels during powder metallurgy processing of the nickel-base disk superalloy Udimet 720. Multiple strain-controlled fatigue tests were then performed on machined specimens with and without shot peened test sections at 427 C and 650 C. The low cycle fatigue lives and failure initiation sites varied as functions of inclusion content, shot peening, and fatigue conditions. A large majority of the failures in as-machined specimens with the introduced inclusions occurred at cracks initiating from inclusions intersecting the specimen surface. These inclusions reduced fatigue life by up to 100X, when compared to lives of material without inclusions residing at specimen surface. Large inclusions produced the greatest reductions in life for tests at low strain ranges and high strain ratios. Shot peening improved life in many cases by reducing the most severe effects of inclusions.

The Protein Structure Initiative Structural Biology Knowledgebase Technology Portal: a structural biology web resource.

PubMed

Gifford, Lida K; Carter, Lester G; Gabanyi, Margaret J; Berman, Helen M; Adams, Paul D

2012-06-01

The Technology Portal of the Protein Structure Initiative Structural Biology Knowledgebase (PSI SBKB; http://technology.sbkb.org/portal/ ) is a web resource providing information about methods and tools that can be used to relieve bottlenecks in many areas of protein production and structural biology research. Several useful features are available on the web site, including multiple ways to search the database of over 250 technological advances, a link to videos of methods on YouTube, and access to a technology forum where scientists can connect, ask questions, get news, and develop collaborations. The Technology Portal is a component of the PSI SBKB ( http://sbkb.org ), which presents integrated genomic, structural, and functional information for all protein sequence targets selected by the Protein Structure Initiative. Created in collaboration with the Nature Publishing Group, the SBKB offers an array of resources for structural biologists, such as a research library, editorials about new research advances, a featured biological system each month, and a functional sleuth for searching protein structures of unknown function. An overview of the various features and examples of user searches highlight the information, tools, and avenues for scientific interaction available through the Technology Portal.

Structure of the ribosome post-recycling complex probed by chemical cross-linking and mass spectrometry

PubMed Central

Kiosze-Becker, Kristin; Ori, Alessandro; Gerovac, Milan; Heuer, André; Nürenberg-Goloub, Elina; Rashid, Umar Jan; Becker, Thomas; Beckmann, Roland; Beck, Martin; Tampé, Robert

2016-01-01

Ribosome recycling orchestrated by the ATP binding cassette (ABC) protein ABCE1 can be considered as the final—or the first—step within the cyclic process of protein synthesis, connecting translation termination and mRNA surveillance with re-initiation. An ATP-dependent tweezer-like motion of the nucleotide-binding domains in ABCE1 transfers mechanical energy to the ribosome and tears the ribosome subunits apart. The post-recycling complex (PRC) then re-initiates mRNA translation. Here, we probed the so far unknown architecture of the 1-MDa PRC (40S/30S·ABCE1) by chemical cross-linking and mass spectrometry (XL-MS). Our study reveals ABCE1 bound to the translational factor-binding (GTPase) site with multiple cross-link contacts of the helix–loop–helix motif to the S24e ribosomal protein. Cross-linking of the FeS cluster domain to the ribosomal protein S12 substantiates an extreme lever-arm movement of the FeS cluster domain during ribosome recycling. We were thus able to reconstitute and structurally analyse a key complex in the translational cycle, resembling the link between translation initiation and ribosome recycling. PMID:27824037

Understanding the causes and consequences of measles virus persistence

PubMed Central

Griffin, Diane E.; Lin, Wen-Hsuan W.; Nelson, Ashley N.

2018-01-01

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10–14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity. PMID:29560260

Understanding the causes and consequences of measles virus persistence.

PubMed

Griffin, Diane E; Lin, Wen-Hsuan W; Nelson, Ashley N

2018-01-01

Measles is an acute systemic viral disease with initial amplification of infection in lymphoid tissue and subsequent spread over 10-14 days to multiple organs. Failure of the innate response to control initial measles virus (MeV) replication is associated with the ability of MeV to inhibit the induction of type I interferon and interferon-stimulated antiviral genes. Rather, the innate response is characterized by the expression of proteins regulated by nuclear factor kappa B and the inflammasome. With eventual development of the adaptive response, the rash appears with immune cell infiltration into sites of virus replication to initiate the clearance of infectious virus. However, MeV RNA is cleared much more slowly than recoverable infectious virus and remains present in lymphoid tissue for at least 6 months after infection. Persistence of viral RNA and protein suggests persistent low-level replication in lymphoid tissue that may facilitate maturation of the immune response, resulting in lifelong protection from reinfection, while persistence in other tissues (for example, the nervous system) may predispose to development of late disease such as subacute sclerosing panencephalitis. Further studies are needed to identify mechanisms of viral clearance and to understand the relationship between persistence and development of lifelong immunity.

Efficient Inversion of Mult-frequency and Multi-Source Electromagnetic Data

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

Gary D. Egbert

2007-03-22

The project covered by this report focused on development of efficient but robust non-linear inversion algorithms for electromagnetic induction data, in particular for data collected with multiple receivers, and multiple transmitters, a situation extremely common in eophysical EM subsurface imaging methods. A key observation is that for such multi-transmitter problems each step in commonly used linearized iterative limited memory search schemes such as conjugate gradients (CG) requires solution of forward and adjoint EM problems for each of the N frequencies or sources, essentially generating data sensitivities for an N dimensional data-subspace. These multiple sensitivities allow a good approximation to themore » full Jacobian of the data mapping to be built up in many fewer search steps than would be required by application of textbook optimization methods, which take no account of the multiplicity of forward problems that must be solved for each search step. We have applied this idea to a develop a hybrid inversion scheme that combines features of the iterative limited memory type methods with a Newton-type approach using a partial calculation of the Jacobian. Initial tests on 2D problems show that the new approach produces results essentially identical to a Newton type Occam minimum structure inversion, while running more rapidly than an iterative (fixed regularization parameter) CG style inversion. Memory requirements, while greater than for something like CG, are modest enough that even in 3D the scheme should allow 3D inverse problems to be solved on a common desktop PC, at least for modest (~ 100 sites, 15-20 frequencies) data sets. A secondary focus of the research has been development of a modular system for EM inversion, using an object oriented approach. This system has proven useful for more rapid prototyping of inversion algorithms, in particular allowing initial development and testing to be conducted with two-dimensional example problems, before approaching more computationally cumbersome three-dimensional problems.« less

Initiation of Detonation in Multiple Shock-Compressed Liquid Explosives

NASA Astrophysics Data System (ADS)

Yoshinaka, A. C.; Zhang, F.; Petel, O. E.; Higgins, A. J.

2006-07-01

Initiation and resulting propagation of detonation via multiple shock reverberations between two high impedance plates has been investigated in amine-sensitized nitromethane. Experiments were designed so that the first reflected shock strength was below the critical value for initiation found previously. Luminosity combined with a distinct pressure hump indicated onset of reaction and successful initiation after double or triple shock reflection off the bottom plate. Final temperature estimates for double or triple shock reflection immediately before initiation lie between 700-720 K, consistent with those found previously for both incident and singly reflected shock initiation.

U.S. Department of Energy's site screening, site selection, and initial characterization for storage of CO2 in deep geological formations

USGS Publications Warehouse

Rodosta, T.D.; Litynski, J.T.; Plasynski, S.I.; Hickman, S.; Frailey, S.; Myer, L.

2011-01-01

The U.S. Department of Energy (DOE) is the lead Federal agency for the development and deployment of carbon sequestration technologies. As part of its mission to facilitate technology transfer and develop guidelines from lessons learned, DOE is developing a series of best practice manuals (BPMs) for carbon capture and storage (CCS). The "Site Screening, Site Selection, and Initial Characterization for Storage of CO2 in Deep Geological Formations" BPM is a compilation of best practices and includes flowchart diagrams illustrating the general decision making process for Site Screening, Site Selection, and Initial Characterization. The BPM integrates the knowledge gained from various programmatic efforts, with particular emphasis on the Characterization Phase through pilot-scale CO2 injection testing of the Validation Phase of the Regional Carbon Sequestration Partnership (RCSP) Initiative. Key geologic and surface elements that suitable candidate storage sites should possess are identified, along with example Site Screening, Site Selection, and Initial Characterization protocols for large-scale geologic storage projects located across diverse geologic and regional settings. This manual has been written as a working document, establishing a framework and methodology for proper site selection for CO2 geologic storage. This will be useful for future CO2 emitters, transporters, and storage providers. It will also be of use in informing local, regional, state, and national governmental agencies of best practices in proper sequestration site selection. Furthermore, it will educate the inquisitive general public on options and processes for geologic CO2 storage. In addition to providing best practices, the manual presents a geologic storage resource and capacity classification system. The system provides a "standard" to communicate storage and capacity estimates, uncertainty and project development risk, data guidelines and analyses for adequate site characterization, and guidelines for reporting estimates within the classification based on each project's status. 

Rating knowledge sharing in cross-domain collaborative filtering.

PubMed

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.

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies.

PubMed

von Kalckreuth, Vera; Konings, Frank; Aaby, Peter; Adu-Sarkodie, Yaw; Ali, Mohammad; Aseffa, Abraham; Baker, Stephen; Breiman, Robert F; Bjerregaard-Andersen, Morten; Clemens, John D; Crump, John A; Cruz Espinoza, Ligia Maria; Deerin, Jessica Fung; Gasmelseed, Nagla; Sow, Amy Gassama; Im, Justin; Keddy, Karen H; Cosmas, Leonard; May, Jürgen; Meyer, Christian G; Mintz, Eric D; Montgomery, Joel M; Olack, Beatrice; Pak, Gi Deok; Panzner, Ursula; Park, Se Eun; Rakotozandrindrainy, Raphaël; Schütt-Gerowitt, Heidi; Soura, Abdramane Bassiahi; Warren, Michelle R; Wierzba, Thomas F; Marks, Florian

2016-03-15

New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

On meta- and mega-analyses for gene–environment interactions

PubMed Central

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M.; Whitehead, Alexander S.; Blair, Ian A.; Vachani, Anil; Clapper, Margie L.; Muscat, Joshua E.; Lazarus, Philip; Scheet, Paul; Moore, Jason H.; Chen, Yong

2017-01-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a “mega” data set, which can be fit by a joint “mega-analysis.” Alternatively, analyses can be done at each site, and results across sites can be combined through a “meta-analysis” procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. PMID:29110346

The role of economics in the QUERI program: QUERI Series

PubMed Central

Smith, Mark W; Barnett, Paul G

2008-01-01

Background The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. Methods We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Results Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Conclusion Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics. PMID:18430199

The Center for HIV/AIDS Vaccine Immunology (CHAVI) Multi-site Quality Assurance Program for Cryopreserved Human Peripheral Blood Mononuclear Cells

PubMed Central

Sarzotti-Kelsoe, Marcella; Needham, Leila K.; Rountree, Wes; Bainbridge, John; Gray, Clive M.; Fiscus, Susan A.; Ferrari, Guido; Stevens, Wendy S.; Stager, Susan L.; Binz, Whitney; Louzao, Raul; Long, Kristy O.; Mokgotho, Pauline; Moodley, Niranjini; Mackay, Melanie; Kerkau, Melissa; McMillion, Takesha; Kirchherr, Jennifer; Soderberg, Kelly A.; Haynes, Barton F.; Denny, Thomas N.

2014-01-01

The Center for HIV/AIDS Vaccine Immunology (CHAVI) consortium was established to determine the host and virus factors associated with HIV transmission, infection and containment of virus replication, with the goal of advancing the development of an HIV protective vaccine. Studies to meet this goal required the use of cryopreserved Peripheral Blood Mononuclear Cell (PBMC) specimens, and therefore it was imperative that a quality assurance (QA) oversight program be developed to monitor PBMC samples obtained from study participants at multiple international sites. Nine site-affiliated laboratories in Africa and the USA collected and processed PBMCs, and cryopreserved PBMC were shipped to CHAVI repositories in Africa and the USA for long-term storage. A three-stage program was designed, based on Good Clinical Laboratory Practices (GCLP), to monitor PBMC integrity at each step of this process. The first stage evaluated the integrity of fresh PBMCs for initial viability, overall yield, and processing time at the site-affiliated laboratories (Stage 1); for the second stage, the repositories determined post-thaw viability and cell recovery of cryopreserved PBMC, received from the site-affiliated laboratories (Stage 2); the third stage assessed the long-term specimen storage at each repository (Stage 3). Overall, the CHAVI PBMC QA oversight program results highlight the relative importance of each of these stages to the ultimate goal of preserving specimen integrity from peripheral blood collection to long-term repository storage. PMID:24910414

On meta- and mega-analyses for gene-environment interactions.

PubMed

Huang, Jing; Liu, Yulun; Vitale, Steve; Penning, Trevor M; Whitehead, Alexander S; Blair, Ian A; Vachani, Anil; Clapper, Margie L; Muscat, Joshua E; Lazarus, Philip; Scheet, Paul; Moore, Jason H; Chen, Yong

2017-12-01

Gene-by-environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega- versus meta-analysis continues. In principle, data from different sites can be integrated at the individual level into a "mega" data set, which can be fit by a joint "mega-analysis." Alternatively, analyses can be done at each site, and results across sites can be combined through a "meta-analysis" procedure without integrating individual level data across sites. Although mega-analysis has been advocated in several recent initiatives, meta-analysis has the advantages of simplicity and feasibility, and has recently led to several important findings in identifying main genetic effects. In this paper, we conducted empirical and simulation studies, using data from a G × E study of lung cancer, to compare the mega- and meta-analyses in four commonly used G × E analyses under the scenario that the number of studies is small and sample sizes of individual studies are relatively large. We compared the two data integration approaches in the context of fixed effect models and random effects models separately. Our investigations provide valuable insights in understanding the differences between mega- and meta-analyses in practice of combining small number of studies in identifying G × E interactions. © 2017 WILEY PERIODICALS, INC.

The role of economics in the QUERI program: QUERI Series.

PubMed

Smith, Mark W; Barnett, Paul G

2008-04-22

The United States (U.S.) Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has implemented economic analyses in single-site and multi-site clinical trials. To date, no one has reviewed whether the QUERI Centers are taking an optimal approach to doing so. Consistent with the continuous learning culture of the QUERI Program, this paper provides such a reflection. We present a case study of QUERI as an example of how economic considerations can and should be integrated into implementation research within both single and multi-site studies. We review theoretical and applied cost research in implementation studies outside and within VA. We also present a critique of the use of economic research within the QUERI program. Economic evaluation is a key element of implementation research. QUERI has contributed many developments in the field of implementation but has only recently begun multi-site implementation trials across multiple regions within the national VA healthcare system. These trials are unusual in their emphasis on developing detailed costs of implementation, as well as in the use of business case analyses (budget impact analyses). Economics appears to play an important role in QUERI implementation studies, only after implementation has reached the stage of multi-site trials. Economic analysis could better inform the choice of which clinical best practices to implement and the choice of implementation interventions to employ. QUERI economics also would benefit from research on costing methods and development of widely accepted international standards for implementation economics.

Unifying Screening Processes Within the PROSPR Consortium: A Conceptual Model for Breast, Cervical, and Colorectal Cancer Screening

PubMed Central

Kim, Jane J.; Schapira, Marilyn M.; Tosteson, Anna N. A.; Zauber, Ann G.; Geiger, Ann M.; Kamineni, Aruna; Weaver, Donald L.; Tiro, Jasmin A.

2015-01-01

General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute–funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. PMID:25957378

The Duke Endowment Child Abuse Prevention Initiative: A Midpoint Assessment

ERIC Educational Resources Information Center

Daro, Deborah; Huang, Lee Ann; English, Brianna

2009-01-01

The Duke Endowment launched its Child Abuse Prevention Initiative in 2002 by funding two program sites, the Durham Family Initiative in Durham, North Carolina, and Strong Communities in Greenville, South Carolina. Both sites aimed to reduce rates of child abuse, improve parenting practices and behaviors, strengthen community service systems, and…

Implementation of Enhanced Recovery After Surgery: a strategy to transform surgical care across a health system.

PubMed

Gramlich, Leah M; Sheppard, Caroline E; Wasylak, Tracy; Gilmour, Loreen E; Ljungqvist, Olle; Basualdo-Hammond, Carlota; Nelson, Gregg

2017-05-19

Enhanced Recovery After Surgery (ERAS) programs have been shown to have a positive impact on outcome. The ERAS care system includes an evidence-based guideline, an implementation program, and an interactive audit system to support practice change. The purpose of this study is to describe the use of the Theoretic Domains Framework (TDF) in changing surgical care and application of the Quality Enhancement Research Initiative (QUERI) model to analyze end-to-end implementation of ERAS in colorectal surgery across multiple sites within a single health system. The ultimate intent of this work is to allow for the development of a model for spread, scale, and sustainability of ERAS in Alberta Health Services (AHS). ERAS for colorectal surgery was implemented at two sites and then spread to four additional sites. The ERAS Interactive Audit System (EIAS) was used to assess compliance with the guidelines, length of stay, readmissions, and complications. Data sources informing knowledge translation included surveys, focus groups, interviews, and other qualitative data sources such as minutes and status updates. The QUERI model and TDF were used to thematically analyze 189 documents with 2188 quotes meeting the inclusion criteria. Data sources were analyzed for barriers or enablers, organized into a framework that included individual to organization impact, and areas of focus for guideline implementation. Compliance with the evidence-based guidelines for ERAS in colorectal surgery at baseline was 40%. Post implementation compliance, consistent with adoption of best practice, improved to 65%. Barriers and enablers were categorized as clinical practice (22%), individual provider (26%), organization (19%), external environment (7%), and patients (25%). In the Alberta context, 26% of barriers and enablers to ERAS implementation occurred at the site and unit levels, with a provider focus 26% of the time, a patient focus 26% of the time, and a system focus 22% of the time. Using the ERAS care system and applying the QUERI model and TDF allow for identification of strategies that can support diffusion and sustainment of innovation of Enhanced Recovery After Surgery across multiple sites within a health care system.

BiP clustering facilitates protein folding in the endoplasmic reticulum.

PubMed

Griesemer, Marc; Young, Carissa; Robinson, Anne S; Petzold, Linda

2014-07-01

The chaperone BiP participates in several regulatory processes within the endoplasmic reticulum (ER): translocation, protein folding, and ER-associated degradation. To facilitate protein folding, a cooperative mechanism known as entropic pulling has been proposed to demonstrate the molecular-level understanding of how multiple BiP molecules bind to nascent and unfolded proteins. Recently, experimental evidence revealed the spatial heterogeneity of BiP within the nuclear and peripheral ER of S. cerevisiae (commonly referred to as 'clusters'). Here, we developed a model to evaluate the potential advantages of accounting for multiple BiP molecules binding to peptides, while proposing that BiP's spatial heterogeneity may enhance protein folding and maturation. Scenarios were simulated to gauge the effectiveness of binding multiple chaperone molecules to peptides. Using two metrics: folding efficiency and chaperone cost, we determined that the single binding site model achieves a higher efficiency than models characterized by multiple binding sites, in the absence of cooperativity. Due to entropic pulling, however, multiple chaperones perform in concert to facilitate the resolubilization and ultimate yield of folded proteins. As a result of cooperativity, multiple binding site models used fewer BiP molecules and maintained a higher folding efficiency than the single binding site model. These insilico investigations reveal that clusters of BiP molecules bound to unfolded proteins may enhance folding efficiency through cooperative action via entropic pulling.

Analysis and prediction of Multiple-Site Damage (MSD) fatigue crack growth

NASA Technical Reports Server (NTRS)

Dawicke, D. S.; Newman, J. C., Jr.

1992-01-01

A technique was developed to calculate the stress intensity factor for multiple interacting cracks. The analysis was verified through comparison with accepted methods of calculating stress intensity factors. The technique was incorporated into a fatigue crack growth prediction model and used to predict the fatigue crack growth life for multiple-site damage (MSD). The analysis was verified through comparison with experiments conducted on uniaxially loaded flat panels with multiple cracks. Configuration with nearly equal and unequal crack distribution were examined. The fatigue crack growth predictions agreed within 20 percent of the experimental lives for all crack configurations considered.

Automated statistical matching of multiple tephra records exemplified using five long maar sequences younger than 75 ka, Auckland, New Zealand

NASA Astrophysics Data System (ADS)

Green, Rebecca M.; Bebbington, Mark S.; Cronin, Shane J.; Jones, Geoff

2014-09-01

Detailed tephrochronologies are built to underpin probabilistic volcanic hazard forecasting, and to understand the dynamics and history of diverse geomorphic, climatic, soil-forming and environmental processes. Complicating factors include highly variable tephra distribution over time; difficulty in correlating tephras from site to site based on physical and chemical properties; and uncertain age determinations. Multiple sites permit construction of more accurate composite tephra records, but correctly merging individual site records by recognizing common events and site-specific gaps is complex. We present an automated procedure for matching tephra sequences between multiple deposition sites using stochastic local optimization techniques. If individual tephra age determinations are not significantly different between sites, they are matched and a more precise age is assigned. Known stratigraphy and mineralogical or geochemical compositions are used to constrain tephra matches. We apply this method to match tephra records from five long sediment cores (≤ 75 cal ka BP) in Auckland, New Zealand. Sediments at these sites preserve basaltic tephras from local eruptions of the Auckland Volcanic Field as well as distal rhyolitic and andesitic tephras from Okataina, Taupo, Egmont, Tongariro, and Tuhua (Mayor Island) volcanic centers. The new correlated record compiled is statistically more likely than previously published arrangements from this area.

Laparoendoscopic single site surgery in pediatric urology: does it require specialized tools?

PubMed Central

Patel, Nishant; Santomauro, Michael; Marietti, Sarah; Chiang, George

2016-01-01

ABSTRACT Purpose: To describe our experience utilizing Laparoendoscopic single site (LESS) surgery in pediatric urology. Materials and Methods: Retrospective chart review was performed on LESS urologic procedures from November 2009 through March 2013. A total of 44 patients underwent 54 procedures including: nephrectomy (23), orchiopexy (14), varicocelectomy (9), orchiectomy (2), urachal cyst excision (3), and antegrade continence enema (3) (ACE). Results: Median patient age was 6.9 years old. Estimated blood loss (EBL), ranged from less than 5cc to 47cc for a bilateral nephrectomy. Operative time varied from 56 mins for varicocelectomy to a median of 360 minutes for a bilateral nephroureterectomy. Incision length ranged between 2 and 2.5cm. In our initial experience we used a commercial port. However, as we progressed, we were able to perform the majority of our procedures via adjacent fascial punctures for instrumentation at the single incision site. One patient did require conversion to an open procedure as a result of bleeding. Three complications were noted (6.8%), with two Clavien Grade 3b complications. Two patients required additional procedures at 1-year follow-up. Conclusions: The use of LESS applies to many pediatric urologic procedures, ideally for ablative procedures or simple reconstructive efforts. The use of adjacent fascial puncture sites for instrumentation can obviate the need for a commercial port or multiple trocars. PMID:27256182

Outcome of and prognostic factors for relapse in children and adolescents with mature B-cell lymphoma and leukemia treated in three consecutive prospective "Lymphomes Malins B" protocols. A Société Française des Cancers de l'Enfant study.

PubMed

Jourdain, Anne; Auperin, Anne; Minard-Colin, Véronique; Aladjidi, Nathalie; Zsiros, Josef; Coze, Carole; Gandemer, Virginie; Bertrand, Yves; Leverger, Guy; Bergeron, Christophe; Michon, Jean; Patte, Catherine

2015-06-01

To describe relapsed B-cell lymphoma or leukemia in children/adolescents treated with a "Lymphomes Malins B" regimen and their outcome and to identify prognostic factors for survival, we studied relapses in the LMB89, 96 and 2001 studies of the Société Française d'Oncologie Pédiatrique (Société Française des Cancers de l'Enfant). Therapeutic guidelines at relapse were to obtain a second complete remission and to consolidate the remission with high-dose chemotherapy followed by autologous stem-cell transplantation. Between July 1989 and March 2007, 67 patients of 1322 (5%) relapsed: 57 had Burkitt lymphoma and 10 had large-cell histology. Three patients were initially treated in risk group A, 41 in group B and 23 in group C. Thirty-three patients had a relapse in one site (15 in the central nervous system) and 34 at multiple sites. Sixty-five patients received salvage chemotherapy and 33 achieved complete remission. Forty-one patients also received high-dose chemotherapy followed by autologous (n=33) or allogeneic (n=8) transplantation. With a median follow-up of 6.4 years, the 5-year survival rate was 29.9%. Nineteen patients were still alive, all but one (group A) received consolidation treatment. Multivariate analysis showed the following factors to be significantly associated with better survival: relapse at one site (P=0.0006), large-cell histology (P=0.012), initial prognostic group A or B with lactate dehydrogenase level below twice the normal value (P=0.005), and time to relapse more than 6 months (P=0.04). Copyright© Ferrata Storti Foundation.

The clinical effect of acellular dermal matrix on gingival thickness and root coverage compared to coronally positioned flap alone.

PubMed

Woodyard, James G; Greenwell, Henry; Hill, Margaret; Drisko, Connie; Iasella, John M; Scheetz, James

2004-01-01

The primary aim of this randomized, controlled, blinded, clinical investigation was to compare the coronally positioned flap (CPF) plus an acellular dermal matrix (ADM) allograft to CPF alone to determine their effect on gingival thickness and percent root coverage. Twenty-four subjects with one Miller Class I or II buccal recession defect of > or = 3 mm were treated with a CPF plus ADM or a CPF alone. Multiple additional recession sites were treated with the same flap procedure, and all sites were studied for 6 months. Tissue thickness was measured at the sulcus base and at the mucogingival junction of all teeth, with an SDM ultrasonic gingival thickness meter. For the ADM sites, mean initial recession of 3.46 mm was reduced to 0.04 mm for defect coverage of 3.42 mm or 99% (P < 0.05). For the CPF group, mean initial recession of 3.27 mm was reduced to 1.08 mm for defect coverage of 2.19 mm or 67% (P < 0.05). The difference between ADM and CPF groups was statistically significant (P < 0.05). Marginal soft-tissue thickness was increased by 0.40 mm (P < 0.05) for the ADM group, whereas the CPF group remained essentially unchanged. Keratinized tissue was increased for the ADM group by 0.81 mm (P < 0.05), whereas the CPF group increased by 0.33 mm (P > 0.05). No additional root coverage was gained due to creeping attachment between 2 and 6 months for either group. Treatment with a CPF plus an ADM allograft significantly increased gingival thickness when compared with a CPF alone. Recession defect coverage was significantly improved with the use of ADM.

STATIC AND KINETIC SITE-SPECIFIC PROTEIN-DNA PHOTOCROSSLINKING: ANALYSIS OF BACTERIAL TRANSCRIPTION INITIATION COMPLEXES

PubMed Central

Naryshkin, Nikolai; Druzhinin, Sergei; Revyakin, Andrei; Kim, Younggyu; Mekler, Vladimir; Ebright, Richard H.

2009-01-01

Static site-specific protein-DNA photocrosslinking permits identification of protein-DNA interactions within multiprotein-DNA complexes. Kinetic site-specific protein-DNA photocrosslinking--involving rapid-quench-flow mixing and pulsed-laser irradiation--permits elucidation of pathways and kinetics of formation of protein-DNA interactions within multiprotein-DNA complexes. We present detailed protocols for application of static and kinetic site-specific protein-DNA photocrosslinking to bacterial transcription initiation complexes. PMID:19378179

Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design

PubMed Central

Rohena, Cristina C.; Telang, Nakul S.; Da, Chenxiao; Risinger, April L.; Sikorski, James A.; Kellogg, Glen E.; Gupton, John T.

2016-01-01

A refined model of the colchicine site on tubulin was used to design an improved analog of the pyrrole parent compound, JG-03-14. The optimized compound, NT-7-16, was evaluated in biological assays that confirm that it has potent activities as a new colchicine site microtubule depolymerizer. NT-7-16 exhibits antiproliferative and cytotoxic activities against multiple cancer cell lines, with IC50 values of 10–16 nM, and it is able to overcome drug resistance mediated by the expression of P-glycoprotein and the βIII isotype of tubulin. NT-7-16 initiated the concentration-dependent loss of cellular microtubules and caused the formation of abnormal mitotic spindles, leading to mitotic accumulation. The direct interaction of NT-7-16 with purified tubulin was confirmed, and it was more potent than combretastatin A-4 in these assays. Binding studies verified that NT-7-16 binds to tubulin within the colchicine site. The antitumor effects of NT-7-16 were evaluated in an MDA-MB-435 xenograft model and it had excellent activity at concentrations that were not toxic. A second compound, NT-9-21, which contains dichloro moieties in place of the 3,5-dibromo substituents of NT-7-16, had a poorer fit within the colchicine site as predicted by modeling and the Hydropathic INTeractions score. Biological evaluations showed that NT-9-21 has 10-fold lower potency than NT-7-16, confirming the modeling predictions. These studies highlight the value of the refined colchicine-site model and identify a new pyrrole-based colchicine-site agent with potent in vitro activities and promising in vivo antitumor actions. PMID:26655304

A comparative study of rhodopsin function in the great bowerbird (P tilonorhynchus nuchalis): Spectral tuning and light‐activated kinetics

PubMed Central

van Hazel, Ilke; Dungan, Sarah Z.; Hauser, Frances E.; Morrow, James M.; Endler, John A.

2016-01-01

Abstract Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well‐characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein‐coupled receptors. While this substitution is present in some dim‐light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site‐directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue‐shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light‐activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure‐function as well as their evolutionary significance for dim‐light vision across vertebrates. PMID:26889650

Atypical anticipatory postural adjustments during gait initiation among individuals with sub-acute stroke.

PubMed

Rajachandrakumar, Roshanth; Fraser, Julia E; Schinkel-Ivy, Alison; Inness, Elizabeth L; Biasin, Lou; Brunton, Karen; McIlroy, William E; Mansfield, Avril

2017-02-01

Anticipatory postural adjustments, executed prior to gait initiation, help preserve lateral stability when stepping. Atypical patterns of anticipatory activity prior to gait initiation may occur in individuals with unilateral impairment (e.g., stroke). This study aimed to determine the prevalence, correlates, and consequences of atypical anticipatory postural adjustment patterns prior to gait initiation in a sub-acute stroke population. Forty independently-ambulatory individuals with sub-acute stroke stood on two force plates and initiated gait at a self-selected speed. Medio-lateral centre of pressure displacement was calculated and used to define anticipatory postural adjustments (shift in medio-lateral centre of pressure >10mm from baseline). Stroke severity, motor recovery, and functional balance and mobility status were also obtained. Three patterns were identified: single (typical), absent (atypical), and multiple (atypical) anticipatory postural adjustments. Thirty-five percent of trials had atypical anticipatory postural adjustments (absent and multiple). Frequency of absent anticipatory postural adjustments was negatively correlated with walking speed. Multiple anticipatory postural adjustments were more prevalent when leading with the non-paretic than the paretic limb. Trials with multiple anticipatory postural adjustments had longer duration of anticipatory postural adjustment and time to foot-off, and shorter unloading time than trials with single anticipatory postural adjustments. A high prevalence of atypical anticipatory control prior to gait initiation was found in individuals with stroke. Temporal differences were identified with multiple anticipatory postural adjustments, indicating altered gait initiation. These findings provide insight into postural control during gait initiation in individuals with sub-acute stroke, and may inform interventions to improve ambulation in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Foothill yellow-legged frog (Rana boylii) oviposition site choice at multiple spatial scales

Treesearch

Amy J. Lind; Hartwell H. Welsh; Clara A. Wheeler

2016-01-01

Studies of resource selection at multiple scales are critical to understanding ecological and evolutionary attributes of a species. We analyzed relative abundance, habitat use, and oviposition site selection of Foothill Yellow-Legged Frogs (Rana boylii) at 11 localities across two geographic regions in California (northern Coast Range and Sierra...

Person Name Disambiguation in the Multicultural and Online Setting

ERIC Educational Resources Information Center

Treeratpituk, Pucktada

2012-01-01

With the recent rise in popularity of social network sites, more and more personal information is becoming available online. Since a person's information is generally available in various formats across multiple sites, there are ever increasing interests in consolidating such personal information from multiple information sources. The goal of…

Imbalanced multi-modal multi-label learning for subcellular localization prediction of human proteins with both single and multiple sites.

PubMed

He, Jianjun; Gu, Hong; Liu, Wenqi

2012-01-01

It is well known that an important step toward understanding the functions of a protein is to determine its subcellular location. Although numerous prediction algorithms have been developed, most of them typically focused on the proteins with only one location. In recent years, researchers have begun to pay attention to the subcellular localization prediction of the proteins with multiple sites. However, almost all the existing approaches have failed to take into account the correlations among the locations caused by the proteins with multiple sites, which may be the important information for improving the prediction accuracy of the proteins with multiple sites. In this paper, a new algorithm which can effectively exploit the correlations among the locations is proposed by using gaussian process model. Besides, the algorithm also can realize optimal linear combination of various feature extraction technologies and could be robust to the imbalanced data set. Experimental results on a human protein data set show that the proposed algorithm is valid and can achieve better performance than the existing approaches.

Calculating the habitable zones of multiple star systems with a new interactive Web site

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

Müller, Tobias W. A.; Haghighipour, Nader

We have developed a comprehensive methodology and an interactive Web site for calculating the habitable zone (HZ) of multiple star systems. Using the concept of spectral weight factor, as introduced in our previous studies of the calculations of HZ in and around binary star systems, we calculate the contribution of each star (based on its spectral energy distribution) to the total flux received at the top of the atmosphere of an Earth-like planet, and use the models of the HZ of the Sun to determine the boundaries of the HZ in multiple star systems. Our interactive Web site for carryingmore » out these calculations is publicly available at http://astro.twam.info/hz. We discuss the details of our methodology and present its application to some of the multiple star systems detected by the Kepler space telescope. We also present the instructions for using our interactive Web site, and demonstrate its capabilities by calculating the HZ for two interesting analytical solutions of the three-body problem.« less

MicrobeWorld Radio and Communications Initiative

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

Barbara Hyde

2006-11-22

MicrobeWorld is a 90-second feature broadcast daily on more than 90 public radio stations and available from several sources as a podcast, including www.microbeworld.org. The feature has a strong focus on the use and adapatbility of microbes as alternative sources of energy, in bioremediation, their role in climate, and especially the many benefits and scientific advances that have resulting from decoding microbial genomes. These audio features are permanantly archived on an educational outreach site, microbeworld.org, where they are linked to the National Science Education Standards. They are also being used by instructors at all levels to introduce students to themore » multiple roles and potential of microbes, including a pilot curriculum program for middle-school students in New York.« less

Assessment of practicality of remote sensing techniques for a study of the effects of strip mining in Alabama

NASA Technical Reports Server (NTRS)

Hughes, T. H.; Dillion, A. C., III; White, J. R., Jr.; Drummond, S. E., Jr.; Hooks, W. G.

1975-01-01

Because of the volume of coal produced by strip mining, the proximity of mining operations, and the diversity of mining methods (e.g. contour stripping, area stripping, multiple seam stripping, and augering, as well as underground mining), the Warrior Coal Basin seemed best suited for initial studies on the physical impact of strip mining in Alabama. Two test sites, (Cordova and Searles) representative of the various strip mining techniques and environmental problems, were chosen for intensive studies of the correlation between remote sensing and ground truth data. Efforts were eventually concentrated in the Searles Area, since it is more accessible and offers a better opportunity for study of erosional and depositional processes than the Cordova Area.

Superfund Redevelopment Initiative Quarterly Webinar Series

EPA Pesticide Factsheets

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.

Non Secretory Multiple Myeloma With Extensive Extramedullary Plasmacytoma: A Diagnostic Dilemma

PubMed Central

Low, Soo Fin; Mohd Tap, Nor Hanani; Kew, Thean Yean; Ngiu, Chai Soon; Sridharan, Radhika

2015-01-01

Multiple myeloma (MM) is characterized by progressive proliferation of malignant plasma cells, usually initiating in the bone marrow. MM can affect any organ; a total of 7 - 18% of patients with MM demonstrate extramedullary involvement at diagnosis. Non-secretory multiple myeloma (NSMM) is a rare variant that accounts for 1 - 5% of all cases of multiple myeloma. The disease is characterized by the absence of monoclonal gammopathy in serum and urine electrophoresis. Our case report highlights the diagnostic challenge of a case of NSMM with extensive extramedullary involvement in a young female patient who initially presented with right shoulder pain and bilateral breasts lumps. Skeletal survey showed multiple lytic bony lesions. The initial diagnosis was primary breast carcinoma with osseous metastases. No monoclonal gammopathy was found in the serum or urine electrophoresis. Bone marrow and breast biopsies revealed marked plasmacytosis. The diagnosis was delayed for a month in view of the lack of clinical suspicion of multiple myeloma in a young patient and scant biochemical expression of non-secretory type of multiple myeloma. PMID:26528383

Evaluation of the Deadly Liver Mob program: insights for roll-out and scale-up of a pilot program to engage Aboriginal Australians in hepatitis C and sexual health education, screening, and care.

PubMed

Treloar, Carla; Hopwood, Max; Cama, Elena; Saunders, Veronica; Jackson, L Clair; Walker, Melinda; Ooi, Catriona; Ubrihien, Ashley; Ward, James

2018-02-01

Deadly Liver Mob (DLM) is a peer-driven, incentivised health promotion program aimed at increasing understanding of hepatitis C, promoting harm reduction in relation to injecting drug use, and linking participants to screening for hepatitis C, other blood borne viruses and sexually transmissible infections among Aboriginal people in Western Sydney, NSW. This paper presents the evaluation of a pilot study examining the acceptability of the program as a first step of a scalability assessment. Deadly Liver Mob operated in co-located needle and syringe programs and sexual health clinics in two sites: (Site 1: two and a half years for 2 days/week; Site 2: 1 year for 1 day per week). Comparisons were made of the proportion of Aboriginal clients (Site 1) and occasions of service provided to Aboriginal clients (Site 2) in the 12 months prior and post-introduction of DLM. Interviews were conducted with 13 staff involved in delivery of DLM and with 19 clients. A total of 655 and 55 Aboriginal clients, respectively, attended Site 1 and Site 2 for health education. The proportion of Aboriginal clients attending both sites was significantly higher during the DLM compared with prior to its implementation. Of those attending for health education, 79 and 73%, respectively, attended screening following education. DLM clients strongly endorsed the program. Some staff were concerned about workforce capacity to effectively engage Aboriginal clients with multiple and complex needs, managing the differing aims of the participating services involved, and about offering of incentives for attendance at health services. While acceptability was high among staff and clients and preliminary results show high engagement with Aboriginal communities, this evaluation of a pilot program raises some issues to consider in scale up of DLM to other sites. The initiation of additional DLM sites should address issues of alignment with governing strategies and workforce capacity.

Recent Multidisciplinary Research Initiatives and IODP Drilling in the South China Sea

NASA Astrophysics Data System (ADS)

Lin, J.; Li, C. F.; Wang, P.; Kulhanek, D. K.

2016-12-01

The South China Sea (SCS) is the largest low-latitude marginal sea in the world. Its formation and evolution are linked to the complex continental-oceanic tectonic interaction of the Eurasian, Pacific, and Indo-Australian plates. Despite its relatively small size and short history, the SCS has undergone nearly a complete Wilson cycle from continental break-up to seafloor spreading to subduction, serving as a natural laboratory for studying the linkages between tectonic, volcanic, and oceanic processes. The last several years have witnessed significant progress in investigation of the SCS through comprehensive research programs using multidisciplinary approaches and enhanced international collaboration. The International Ocean Discovery Program (IODP) Expedition 349 drilled and cored five sites in the SCS in 2014. The expedition successfully obtained the first basaltic rock samples of the SCS relict spreading center, discovered large and frequent deep-sea turbidity events, and sampled multiple seamount volcaniclastic layers. In addition, high-resolution near-seafloor magnetic surveys were conducted in the SCS with survey lines passing near some of the IODP drilling sites. Together the IODP drilling and deep-tow magnetic survey results confirmed, for the first time, that the entire SCS basin might have stopped seafloor spreading at similar ages in early Miocene, providing important constraints on marginal sea geodynamic models. In 2007, IODP Expeditions 367 and 368 will drill the northern margin of the SCS to investigate the mechanisms of rifting to spreading processes. Meanwhile, major progress in studying the SCS processes has also been made through comprehensive multidisciplinary programs, for example, the eight-year-long "South China Sea Deep" initiative, which also supports and encourages strong international collaboration. This presentation will highlight the recent multidisciplinary research initiatives in investigation of the SCS and the important role of international collaboration.

Different enzyme kinetic models.

PubMed

Seibert, Eleanore; Tracy, Timothy S

2014-01-01

As described in Chapter 2 , a large number of enzymatic reactions can be adequately described by Michaelis-Menten kinetics. The Michaelis-Menten equation represents a rectangular hyperbola, with a y-asymptote at the V max value. In many cases, more complex kinetic models are required to explain the observed data. Atypical kinetic profiles are believed to arise from the simultaneous binding of multiple molecules within the active site of the enzyme (Tracy and Hummel, Drug Metab Rev 36:231-242, 2004). Several cytochromes P450 have large active sites that enable binding of multiple molecules (Wester et al. J Biol Chem 279:35630-35637, 2004; Yano et al. J Biol Chem 279:38091-38094, 2004). Thus, atypical kinetics are not uncommon in in vitro drug metabolism studies. This chapter covers enzyme kinetic reactions in which a single enzyme has multiple binding sites for substrates and/or inhibitors as well as reactions catalyzed by multiple enzymes.

Uncertainty Analysis Framework - Hanford Site-Wide Groundwater Flow and Transport Model

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

Cole, Charles R.; Bergeron, Marcel P.; Murray, Christopher J.

2001-11-09

Pacific Northwest National Laboratory (PNNL) embarked on a new initiative to strengthen the technical defensibility of the predictions being made with a site-wide groundwater flow and transport model at the U.S. Department of Energy Hanford Site in southeastern Washington State. In FY 2000, the focus of the initiative was on the characterization of major uncertainties in the current conceptual model that would affect model predictions. The long-term goals of the initiative are the development and implementation of an uncertainty estimation methodology in future assessments and analyses using the site-wide model. This report focuses on the development and implementation of anmore » uncertainty analysis framework.« less

Feasibility Study of Biopower in East Helena, Montana. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

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

Moriarty, K.

2013-02-01

The U.S. Environmental Protection Agency (EPA) developed the RE-Powering America's Land initiative to reuse contaminated sites for renewable energy generation when aligned with the community's vision for the site. The former American Smelting and Refining Company (Asarco) smelter in East Helena, Montana, was selected for a feasibility study under the initiative. Biomass was chosen as the renewable energy resource based on the wood products industry in the area. Biopower was selected as the technology based on Montana's renewable portfolio standard (RPS) requiring utilities to purchase renewable power.

Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial.

PubMed

Mitha, Essack; Schumacher, H Ralph; Fouche, Leon; Luo, Shue-Fen; Weinstein, Steven P; Yancopoulos, George D; Wang, Jian; King-Davis, Shirletta; Evans, Robert R

2013-07-01

To evaluate the efficacy and safety of IL-1 inhibitor rilonacept (IL-1 Trap) for gout flare (GF) prevention during initiation of uric acid-lowering therapy (ULT) with allopurinol in a multiregional phase 3 clinical trial. Hyperuricaemic adults (n = 248) from South Africa, Germany and Asia with gout and two or more GFs within the past year were initiated on allopurinol and randomized 1:1:1 to once-weekly s.c. treatment with placebo (PBO), rilonacept 80 mg (R80) or rilonacept 160 mg (R160) for 16 weeks. The primary endpoint was the number of GFs per patient through week 16. The population was predominantly male and racially diverse (white, 53.2%; Asian, 33.1%; black, 13.7%). Across treatments, most patients completed the study (87.8-92.9%). At 16 weeks the mean number of GFs per patient was reduced by 71.3% with R80 (0.35) and by 72.6% with R160 (0.34) relative to PBO (1.23; both P < 0.0001). The proportion of patients without GFs was higher with R80 (74.4%) and R160 (79.5%) than with PBO (43.9%; both P ≤ 0.0001), and the proportions of patients on rilonacept with multiple GFs were significantly lower (P < 0.001). Overall, the incidence of adverse events (AEs) was similar between PBO (61.0%) and rilonacept (65.1%). Injection site reactions, generally mild, were the most frequent AE with rilonacept (1.2% PBO, 12.2% R80 and 17.9% R160); none of these injection site reactions led to withdrawal. There were no study drug-related serious AEs or deaths. Rilonacept significantly reduced the occurrence of GFs associated with initiation of ULT, with >70% of patients having no flares, and demonstrated an acceptable safety and tolerability profile. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00958438.

Retention in care, resource utilization, and costs for adults receiving antiretroviral therapy in Zambia: a retrospective cohort study

PubMed Central

2014-01-01

Background Of the estimated 800,000 adults living with HIV in Zambia in 2011, roughly half were receiving antiretroviral therapy (ART). As treatment scale up continues, information on the care provided to patients after initiating ART can help guide decision-making. We estimated retention in care, the quantity of resources utilized, and costs for a retrospective cohort of adults initiating ART under routine clinical conditions in Zambia. Methods Data on resource utilization (antiretroviral [ARV] and non-ARV drugs, laboratory tests, outpatient clinic visits, and fixed resources) and retention in care were extracted from medical records for 846 patients who initiated ART at ≥15 years of age at six treatment sites between July 2007 and October 2008. Unit costs were estimated from the provider’s perspective using site- and country-level data and are reported in 2011 USD. Results Patients initiated ART at a median CD4 cell count of 145 cells/μL. Fifty-nine percent of patients initiated on a tenofovir-containing regimen, ranging from 15% to 86% depending on site. One year after ART initiation, 75% of patients were retained in care. The average cost per patient retained in care one year after ART initiation was $243 (95% CI, $194-$293), ranging from $184 (95% CI, $172-$195) to $304 (95% CI, $290-$319) depending on site. Patients retained in care one year after ART initiation received, on average, 11.4 months’ worth of ARV drugs, 1.5 CD4 tests, 1.3 blood chemistry tests, 1.4 full blood count tests, and 6.5 clinic visits with a doctor or clinical officer. At all sites, ARV drugs were the largest cost component, ranging from 38% to 84% of total costs, depending on site. Conclusions Patients initiate ART late in the course of disease progression and a large proportion drop out of care after initiation. The quantity of resources utilized and costs vary widely by site, and patients utilize a different mix of resources under routine clinical conditions than if they were receiving fully guideline-concordant care. Improving retention in care and guideline concordance, including increasing the use of tenofovir in first-line ART regimens, may lead to increases in overall treatment costs. PMID:24684772

Managing data from multiple disciplines, scales, and sites to support synthesis and modeling

USGS Publications Warehouse

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.

Standardizing the intrinsic brain: Towards robust measurement of inter-individual variation in 1000 functional connectomes

PubMed Central

Yan, Chao-Gan; Craddock, R. Cameron; Zuo, Xi-Nian; Zang, Yu-Feng; Milham, Michael P.

2014-01-01

As researchers increase their efforts to characterize variations in the functional connectome across studies and individuals, concerns about the many sources of nuisance variation present and their impact on resting state fMRI (R-fMRI) measures continue to grow. Although substantial within-site variation can exist, efforts to aggregate data across multiple sites such as the 1000 Functional Connectomes Project (FCP) and International Neuroimaging Data-sharing Initiative (INDI) datasets amplify these concerns. The present work draws upon standardization approaches commonly used in the microarray gene expression literature, and to a lesser extent recent imaging studies, and compares them with respect to their impact on relationships between common R-fMRI measures and nuisance variables (e.g., imaging site, motion), as well as phenotypic variables of interest (age, sex). Standardization approaches differed with regard to whether they were applied post-hoc vs. during pre-processing, and at the individual vs. group level; additionally they varied in whether they addressed additive effects vs. additive + multiplicative effects, and were parametric vs. non-parametric. While all standardization approaches were effective at reducing undesirable relationships with nuisance variables, post-hoc approaches were generally more effective than global signal regression (GSR). Across approaches, correction for additive effects (global mean) appeared to be more important than for multiplicative effects (global SD) for all R-fMRI measures, with the exception of amplitude of low frequency fluctuations (ALFF). Group-level post-hoc standardizations for mean-centering and variance-standardization were found to be advantageous in their ability to avoid the introduction of artifactual relationships with standardization parameters; though results between individual and group-level post-hoc approaches were highly similar overall. While post-hoc standardization procedures drastically increased test–retest (TRT) reliability for ALFF, modest reductions were observed for other measures after post-hoc standardizations—a phenomena likely attributable to the separation of voxel-wise from global differences among subjects (global mean and SD demonstrated moderate TRT reliability for these measures). Finally, the present work calls into question previous observations of increased anatomical specificity for GSR over mean centering, and draws attention to the near equivalence of global and gray matter signal regression. PMID:23631983

A strategy for health promotion at multiple corporate sites.

PubMed

Alexy, B; Eynon, D

1991-02-01

1. The logistical problems associated with delivery of health promotion programs at multiple corporate sites can be addressed through the use of health education packets. 2. The role of the nurse or health coordinator is critical in assisting and guiding the employee as the health plan is executed. 3. Problematic areas related to implementation of programs at remote sites can be alleviated through careful planning and extensive communication. 4. Advertising, input from employees and staff, and follow up are important in the success of a program.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing.

PubMed

Malina, Abba; Cameron, Christopher J F; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-12-08

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification.

PAM multiplicity marks genomic target sites as inhibitory to CRISPR-Cas9 editing

PubMed Central

Malina, Abba; Cameron, Christopher J. F.; Robert, Francis; Blanchette, Mathieu; Dostie, Josée; Pelletier, Jerry

2015-01-01

In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification. PMID:26644285

Desert Research and Technology Studies (RATS) 2007 Field Campaign Objectives and Results

NASA Technical Reports Server (NTRS)

Kosmo, Joseph; Romig, Barbara

2008-01-01

Desert "RATS" (Research and Technology Studies) is a combined, multi-discipline group of inter-NASA center scientists and engineers, net-working and collaborating with representatives of industry and academia, for the purpose of conducting planetary surface exploration-focused remote field exercises. These integrated testing exercises conducted under representative analog Lunar and Mars surface terrain conditions, provide NASA the capability to validate experimental prototype hardware and software systems as well as to evaluate and develop mission operational techniques in order to identify and establish technical requirements and identify potential technology "gaps" applicable for future planetary human exploration. The 2007 D-RATS field campaign test activities were initiated based on the major themes and objectives of a notional 5-year plan developed for conducting relative analog test activities in support of the engineering evaluation and assessment of various system architectural requirements, conceptual prototype support equipment and selected technologies necessary for the establishment of a lunar outpost. Specifically, the major objectives included measuring task efficiency during robot, human, and human-robot interactive tasks associated with lunar outpost site surveying and reconnaissance activities and deployment of a representative solar panel power and distribution system. In addition, technology demonstrations were conducted with a new Lithium-ion battery and autonomous software to coordinate multiple robot activities. Secondary objectives were evaluating airlock concept mockups and prototype removable space suit over-garment elements for dust mitigation, and upgrades to the prototype extravehicular activities (EVA) communication and information system. Dry run test activities, prior to testing at a designated remote field site location, were initially conducted at the Johnson Space Center (JSC) Remote Field Demonstration Test Site. This is a multi-acre external test site located at JSC and has detailed representative terrain features simulating both Lunar and Mars surface characteristics. Both the local JSC and remote field test sites have terrain conditions that are representative and characteristic of both the Moon and Mars, such as strewn rock and volcanic ash fields, craters, rolling plains, hills, gullies, slopes, and outcrops. The D-RATS 2007 field campaign, representing the completion of its tenth year of analog testing, was conducted at the large Cinder Lake volcanic ash bed area adjacent to Flagstaff, Arizona.

Late Eocene stable isotope stratigraphy of North Atlantic IODP Site U1411: Orbitally paced climatic heartbeat at the close of the Eocene greenhouse

NASA Astrophysics Data System (ADS)

Coxall, Helen; Bohaty, Steve; Wilson, Paul; Liebrand, Diederik; Nyberg, Anna; Holmström, Max

2016-04-01

Integrated Ocean Drilling Program (IODP) Expedition 342 drilled sediment drifts on the Newfoundland margin to recover high-resolution records of North Atlantic ocean-climate history and track the evolution of the modern climate system through the Late Cretaceous and Early Cenozoic. An early Paleogene deep-sea benthic stable isotope composite record from multiple Exp. 342 sites is currently in development and will provide a key reference section for investigations of Atlantic and global climate dynamics. This study presents initial results for the late Eocene slice of the composite from Site U1411, located at mid depth (˜2850m Eocene paleodepth) on the Southeast Newfoundland Ridge. Stable oxygen (δ18O) and carbon (δ13C) isotope ratios were measured on 640 samples hosting exceptionally well-preserved epifaunal benthic foraminifera obtained from the microfossil-rich uppermost Eocene clays at 4cm spacing. Sedimentation rates average 2-3 cm/kyr through the late Eocene, such that our sampling resolution is sufficient to capture the dominant Milankovitch frequencies. Late Eocene Site U1411 benthic δ18O values (1.4 to 0.5‰ VPDB) are comparable to the Pacific and elsewhere in the Atlantic at similar depths; however, δ13C is lower by ˜0.5 ‰ with values intermediate between those of the Southern Labrador Sea to the north (-1 to 0) and mid latitude/South Atlantic (0.5 to 1.5) to the south, suggesting poorly ventilated bottom waters in the late Eocene North Atlantic and limited production of North Atlantic deep water. Applying the initial shipboard magneto-biostratigraphic age framework, the Site U1411 benthic δ13C and δ18O records display clear cyclicity on orbital timescales. Spectral analysis of the raw unfiltered datasets identifies eccentricity (400 and 100 kyr), obliquity (40 kyr) and precession (˜20 kyr) signals imprinted on our time series, revealing distinct climatic heart beats in the late Eocene prior to the transition into the 'ice house'.

History and evaluation of national-scale geochemical data sets for the United States

USGS Publications Warehouse

Smith, David B.; Smith, Steven M.; Horton, John D.

2013-01-01

Six national-scale, or near national-scale, geochemical data sets for soils or stream sediments exist for the United States. The earliest of these, here termed the ‘Shacklette’ data set, was generated by a U.S. Geological Survey (USGS) project conducted from 1961 to 1975. This project used soil collected from a depth of about 20 cm as the sampling medium at 1323 sites throughout the conterminous U.S. The National Uranium Resource Evaluation Hydrogeochemical and Stream Sediment Reconnaissance (NURE-HSSR) Program of the U.S. Department of Energy was conducted from 1975 to 1984 and collected either stream sediments, lake sediments, or soils at more than 378,000 sites in both the conterminous U.S. and Alaska. The sampled area represented about 65% of the nation. The Natural Resources Conservation Service (NRCS), from 1978 to 1982, collected samples from multiple soil horizons at sites within the major crop-growing regions of the conterminous U.S. This data set contains analyses of more than 3000 samples. The National Geochemical Survey, a USGS project conducted from 1997 to 2009, used a subset of the NURE-HSSR archival samples as its starting point and then collected primarily stream sediments, with occasional soils, in the parts of the U.S. not covered by the NURE-HSSR Program. This data set contains chemical analyses for more than 70,000 samples. The USGS, in collaboration with the Mexican Geological Survey and the Geological Survey of Canada, initiated soil sampling for the North American Soil Geochemical Landscapes Project in 2007. Sampling of three horizons or depths at more than 4800 sites in the U.S. was completed in 2010, and chemical analyses are currently ongoing. The NRCS initiated a project in the 1990s to analyze the various soil horizons from selected pedons throughout the U.S. This data set currently contains data from more than 1400 sites. This paper (1) discusses each data set in terms of its purpose, sample collection protocols, and analytical methods; and (2) evaluates each data set in terms of its appropriateness as a national-scale geochemical database and its usefulness for national-scale geochemical mapping.

Shared regulatory sites are abundant in the human genome and shed light on genome evolution and disease pleiotropy.

PubMed

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.

Study site characterization. Chapter 2

Treesearch

Chris Potter; Richard Birdsey

2008-01-01

This chapter is an overview of the main site characterization requirements at landscape-scale sampling locations. The overview is organized according to multiple "Site Attribute" headings that require descriptions throughout a given study site area, leading ultimately to a sufficient overall site characterization. Guidance is provided to describe the major...

Multiple sexual partnerships and their correlates among Facebook users in Swaziland: an online cross-sectional study.

PubMed

Lukhele, Bhekumusa Wellington; Techasrivichien, Teeranee; Musumari, Patou Masika; El-Saaidi, Christina; Suguimoto, S Pilar; Ono-Kihara, Masako; Kihara, Masahiro

2016-09-01

Social networking sites (SNSs) have been suggested to facilitate risky sexual activities. However, it is unknown and of concern how SNSs such as Facebook shape risky sexual activities in developing settings such as Swaziland, the country hardest hit by HIV and AIDS. We conducted an online cross-sectional study in 2012 to explore the prevalence of multiple sexual partnerships (MSPs) and their correlates among Facebook users in Swaziland. The response rate was 44.1% (N = 882); relatively, an equal proportion of men 82.7% (341/414) and 82.9% (388/468) women had ever had sex. Of those sexually active, 44.9% of men and 30.7% of women reported having sex with someone they met on Facebook. Approximately half of the participants (61.6% men, 41.0% women and 50.6% total) reported MSPs over the past 12 months. Multiple logistic regression analysis revealed that time spent on Facebook, "finding it easier to initiate a romantic conversation on Facebook" and having had sex with someone met on Facebook were significantly associated with having MSPs (adjusted odds ratio = 1.6-3.8). The potential impact of risky sexual behaviour among Facebook users should be appropriately addressed particularly in high HIV-prevalent settings like Swaziland.

Using Standardized Pre-Posttests to Establish Program Equivalency at Multiple Sites

ERIC Educational Resources Information Center

Ritchie, William F.; Kreitner, David

2005-01-01

Keiser College is a private, for-profit Level II institution with thirteen branch campuses throughout Florida. Most of its academic programs are offered at multiple sites. A major concern has been to establish and maintain the consistency of its academic offerings at all campuses as the College expands. Building on a pre- posttesting mechanism…

Recruitment of local inhibitory networks by horizontal connections in layer 2/3 of ferret visual cortex.

PubMed

Tucker, Thomas R; Katz, Lawrence C

2003-01-01

To investigate how neurons in cortical layer 2/3 integrate horizontal inputs arising from widely distributed sites, we combined intracellular recording and voltage-sensitive dye imaging to visualize the spatiotemporal dynamics of neuronal activity evoked by electrical stimulation of multiple sites in visual cortex. Individual stimuli evoked characteristic patterns of optical activity, while delivering stimuli at multiple sites generated interacting patterns in the regions of overlap. We observed that neurons in overlapping regions received convergent horizontal activation that generated nonlinear responses due to the emergence of large inhibitory potentials. The results indicate that co-activation of multiple sets of horizontal connections recruit strong inhibition from local inhibitory networks, causing marked deviations from simple linear integration.

The meninges: new therapeutic targets for multiple sclerosis.

PubMed

Russi, Abigail E; Brown, Melissa A

2015-02-01

The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Diabetes and Risk of Surgical Site Infection: A systematic review and meta-analysis

PubMed Central

Kaye, Keith S.; Knott, Caitlin; Nguyen, Huong; Santarossa, Maressa; Evans, Richard; Bertran, Elizabeth; Jaber, Linda

2016-01-01

Objective To determine the independent association between diabetes and SSI across multiple surgical procedures. Design Systematic review and meta-analysis. Methods Studies indexed in PubMed published between December 1985 and through July 2015 were identified through the search terms “risk factors” or “glucose” and “surgical site infection”. A total of 3,631 abstracts were identified through the initial search terms. Full texts were reviewed for 522 articles. Of these, 94 articles met the criteria for inclusion. Standardized data collection forms were used to extract study-specific estimates for diabetes, blood glucose levels, and body mass index (BMI). Random-effects meta-analysis was used to generate pooled estimates and meta-regression was used to evaluate specific hypothesized sources of heterogeneity. Results The primary outcome was SSI, as defined by the Centers for Disease Control and Prevention surveillance criteria. The overall effect size for the association between diabetes and SSI was OR=1.53 (95% Predictive Interval 1.11, 2.12, I2: 57.2%). SSI class, study design, or patient BMI did not significantly impact study results in a meta-regression model. The association was higher for cardiac surgery 2.03 (95% Predictive Interval 1.13, 4.05) compared to surgeries of other types (p=0.001). Conclusion These results support the consideration of diabetes as an independent risk factor for SSIs for multiple surgical procedure types. Continued efforts are needed to improve surgical outcomes for diabetic patients. PMID:26503187

Can multidetector CT detect the site of gastrointestinal tract injury in trauma? – A retrospective study

PubMed Central

Panda, Ananya; Kumar, Atin; Gamanagatti, Shivanand; Das, Ranjita; Paliwal, Swati; Gupta, Amit; Kumar, Subodh

2017-01-01

PURPOSE We aimed to assess the performance of computed tomography (CT) in localizing site of traumatic gastrointestinal tract (GIT) injury and determine the diagnostic value of CT signs in site localization. METHODS CT scans of 97 patients with surgically proven GIT or mesenteric injuries were retrospectively reviewed by radiologists blinded to surgical findings. Diagnosis of either GIT or mesenteric injuries was made. In patients with GIT injuries, site of injury and presence of CT signs such as focal bowel wall hyperenhancement, hypoenhancement, wall discontinuity, wall thickening, extramural air, intramural air, perivisceral infiltration, and active vascular contrast leak were evaluated. RESULTS Out of 97 patients, 90 had GIT injuries (70 single site injuries and 20 multiple site injuries) and seven had isolated mesenteric injury. The overall concordance between CT and operative findings for exact site localization was 67.8% (61/90), partial concordance rate was 11.1% (10/90), and discordance rate was 21.1% (19/90). For single site localization, concordance rate was 77.1% (54/70), discordance rate was 21.4% (15/70), and partial concordance rate was 1.4% (1/70). In multiple site injury, concordance rate for all sites of injury was 35% (7/20), partial concordance rate was 45% (9/20), and discordance rate was 20% (4/20). For upper GIT injuries, wall discontinuity was the most accurate sign for localization. For small bowel injury, intramural air and hyperenhancement were the most specific signs for site localization, while for large bowel injury, wall discontinuity and hypoenhancement were the most specific signs. CONCLUSION CT performs better in diagnosing small bowel injury compared with large bowel injury. CT can well predict the presence of multiple site injury but has limited performance in exact localization of all injury sites. PMID:27924777

Concentration-Dependent Multiple Binding Sites on Saliva-Treated Hydroxyapatite for Streptococcus sanguis

PubMed Central

Gibbons, R. J.; Moreno, E. C.; Etherden, I.

1983-01-01

The influence of bacterial cell concentration on estimates of the number of binding sites and the affinity for the adsorption of a strain of Streptococcus sanguis to saliva-treated hydroxyapatite was determined, and the possible presence of multiple binding sites for this organism was tested. The range of concentrations of available bacteria varied from 4.7 × 106 to 5,960 × 106 cells per ml. The numbers of adsorbed bacteria increased over the entire range tested, but a suggestion of a break in an otherwise smooth adsorption isotherm was evident. Values for the number of binding sites and the affinity varied considerably depending upon the range of available bacterial concentrations used to estimate them; high correlation coefficients were obtained in all cases. The use of low bacterial cell concentrations yielded lower values for the number of sites and much higher values for the affinity constant than did the use of high bacterial cell concentrations. When data covering the entire range of bacterial concentrations were employed, values for the number of sites and the affinity were similar to those obtained by using only high bacterial cell concentrations. The simplest explanation for these results is that there are multiple binding sites for S. sanguis on saliva-treated hydroxyapatite surfaces. When present in low concentration, the streptococci evidently attach to more specific high-affinity sites which become saturated when higher bacterial concentrations are employed. The possibility of multiple binding sites was substantiated by comparing estimates of the adsorption parameters from a computer-simulated isotherm with those derived from the experimentally generated isotherm. A mathematical model describing bacterial adsorption to binary binding sites was further evidence for the existence of at least two classes of binding sites for S. sanguis. Far fewer streptococci adsorbed to experimental pellicles prepared from saliva depleted of bacterial aggregating activity when low numbers of streptococci were used, but the magnitude of this difference was considerably less when high streptococcal concentrations were employed. This suggests an association between salivary components which possess bacterial-aggregating activity and bacterial adsorption to high-affinity specific binding sites on saliva-treated hydroxyapatite surfaces. PMID:6822416

CsrA Participates in a PNPase Autoregulatory Mechanism by Selectively Repressing Translation of pnp Transcripts That Have Been Previously Processed by RNase III and PNPase

PubMed Central

Park, Hongmarn; Yakhnin, Helen; Connolly, Michael; Romeo, Tony

2015-01-01

ABSTRACT Csr is a conserved global regulatory system that represses or activates gene expression posttranscriptionally. CsrA of Escherichia coli is a homodimeric RNA binding protein that regulates transcription elongation, translation initiation, and mRNA stability by binding to the 5′ untranslated leader or initial coding sequence of target transcripts. pnp mRNA, encoding the 3′ to 5′ exoribonuclease polynucleotide phosphorylase (PNPase), was previously identified as a CsrA target by transcriptome sequencing (RNA-seq). Previous studies also showed that RNase III and PNPase participate in a pnp autoregulatory mechanism in which RNase III cleavage of the untranslated leader, followed by PNPase degradation of the resulting 5′ fragment, leads to pnp repression by an undefined translational repression mechanism. Here we demonstrate that CsrA binds to two sites in pnp leader RNA but only after the transcript is fully processed by RNase III and PNPase. In the absence of processing, both of the binding sites are sequestered in an RNA secondary structure, which prevents CsrA binding. The CsrA dimer bridges the upstream high-affinity site to the downstream site that overlaps the pnp Shine-Dalgarno sequence such that bound CsrA causes strong repression of pnp translation. CsrA-mediated translational repression also leads to a small increase in the pnp mRNA decay rate. Although CsrA has been shown to regulate translation and mRNA stability of numerous genes in a variety of organisms, this is the first example in which prior mRNA processing is required for CsrA-mediated regulation. IMPORTANCE CsrA protein represses translation of numerous mRNA targets, typically by binding to multiple sites in the untranslated leader region preceding the coding sequence. We found that CsrA represses translation of pnp by binding to two sites in the pnp leader transcript but only after it is processed by RNase III and PNPase. Processing by these two ribonucleases alters the mRNA secondary structure such that it becomes accessible to the ribosome for translation as well as to CsrA. As one of the CsrA binding sites overlaps the pnp ribosome binding site, bound CsrA prevents ribosome binding. This is the first example in which regulation by CsrA requires prior mRNA processing and should link pnp expression to conditions affecting CsrA activity. PMID:26438818

A mathematical analysis of multiple-target SELEX.

PubMed

Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

2010-10-01

SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following statement: For any initial pool of nucleic acids such that all N species are represented, the dynamical system defined by the multiple target SELEX process will converge to a unique subset of nucleic acids, each of whose concentrations depend only upon the total nucleic acid concentration, the initial fractional target distribution (both of which are assumed to be the same from round to round), and the overall limiting association constant. (The overall association constant is the equilibrium constant for the system of MN reactions when viewed as a composite single reaction). This condition is equivalent to the statement that every member of a certain family of chemical potentials at infinite target dilution can have at most one critical point. (The condition replaces the statement for single target SELEX that the dynamical system generated via the process always converges to a pool that contains only the nucleic acid that binds best to the target). This suggests that the effectiveness of multiple target SELEX as a separation procedure may not be as useful as single target SELEX unless the thermodynamic properties of these chemical potentials are well understood.

USEPA SITE PROGRAM APPROACH TO TECHNOLOGY TRANSFER AND REGULATORY ACCEPTANCE

EPA Science Inventory

The USEPA's SITE program was created to meet the demand for innovative technologies for hazardous waste treatment. The primary mission of the SITe Program is to expedite the cleanup of sites on the NPL. These sites often have multiple contaminants in soil and groundwater, and few...

Minute Virus of Mice Initiator Protein NS1 and a Host KDWK Family Transcription Factor Must Form a Precise Ternary Complex with Origin DNA for Nicking To Occur

PubMed Central

Christensen, Jesper; Cotmore, Susan F.; Tattersall, Peter

2001-01-01

Parvoviral rolling hairpin replication generates palindromic genomic concatemers whose junctions are resolved to give unit-length genomes by a process involving DNA replication initiated at origins derived from each viral telomere. The left-end origin of minute virus of mice (MVM), oriL, contains binding sites for the viral initiator nickase, NS1, and parvovirus initiation factor (PIF), a member of the emerging KDWK family of transcription factors. oriL is generated as an active form, oriLTC, and as an inactive form, oriLGAA, which contains a single additional nucleotide inserted between the NS1 and PIF sites. Here we examined the interactions on oriLTC which lead to activation of NS1 by PIF. The two subunits of PIF, p79 and p96, cooperatively bind two ACGT half-sites, which can be flexibly spaced. When coexpressed from recombinant baculoviruses, the PIF subunits preferentially form heterodimers which, in the presence of ATP, show cooperative binding with NS1 on oriL, but this interaction is preferentially enhanced on oriLTC compared to oriLGAA. Without ATP, NS1 is unable to bind stably to its cognate site, but PIF facilitates this interaction, rendering the NS1 binding site, but not the nick site, resistant to DNase I. Varying the spacing of the PIF half-sites shows that the distance between the NS1 binding site and the NS1-proximal half-site is critical for nickase activation, whereas the position of the distal half-site is unimportant. When expressed separately, both PIF subunits form homodimers that bind site specifically to oriL, but only complexes containing p79 activate the NS1 nickase function. PMID:11435581

Bioinformatic prediction and in vivo validation of residue-residue interactions in human proteins

NASA Astrophysics Data System (ADS)

Jordan, Daniel; Davis, Erica; Katsanis, Nicholas; Sunyaev, Shamil

2014-03-01

Identifying residue-residue interactions in protein molecules is important for understanding both protein structure and function in the context of evolutionary dynamics and medical genetics. Such interactions can be difficult to predict using existing empirical or physical potentials, especially when residues are far from each other in sequence space. Using a multiple sequence alignment of 46 diverse vertebrate species we explore the space of allowed sequences for orthologous protein families. Amino acid changes that are known to damage protein function allow us to identify specific changes that are likely to have interacting partners. We fit the parameters of the continuous-time Markov process used in the alignment to conclude that these interactions are primarily pairwise, rather than higher order. Candidates for sites under pairwise epistasis are predicted, which can then be tested by experiment. We report the results of an initial round of in vivo experiments in a zebrafish model that verify the presence of multiple pairwise interactions predicted by our model. These experimentally validated interactions are novel, distant in sequence, and are not readily explained by known biochemical or biophysical features.

A case study of multi-seam coal mine entry stability analysis with strength reduction method

PubMed Central

Tulu, Ihsan Berk; Esterhuizen, Gabriel S; Klemetti, Ted; Murphy, Michael M.; Sumner, James; Sloan, Michael

2017-01-01

In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines. PMID:28239503

A case study of multi-seam coal mine entry stability analysis with strength reduction method.

PubMed

Tulu, Ihsan Berk; Esterhuizen, Gabriel S; Klemetti, Ted; Murphy, Michael M; Sumner, James; Sloan, Michael

2016-03-01

In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines.

Monte Carlo approach in assessing damage in higher order structures of DNA

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Schmidt, J. B.; Holley, W. R.

1994-01-01

We have developed a computer monitor of nuclear DNA in the form of chromatin fibre. The fibres are modeled as a ideal solenoid consisting of twenty helical turns with six nucleosomes per turn. The chromatin model, in combination with are Monte Carlo theory of radiation damage induces by charged particles, based on general features of tack structure and stopping power theory, has been used to evaluate the influence of DNA structure on initial damage. An interesting has emerged from our calculations. Our calculated results predict the existence of strong spatial correlations in damage sites associated with the symmetries in the solenoidal model. We have calculated spectra of short fragments of double stranded DNA produced by multiple double strand breaks induced by both high and low LET radiation. The spectra exhibit peaks at multiples of approximately 85 base pairs (the nucleosome periodicity), and approximately 1000 base pairs (solenoid periodicity). Preliminary experiments to investigate the fragment distributions from irradiated DNA, made by B. Rydberg at Lawrence Berkeley Laboratory, confirm the existence of short DNA fragments and are in substantial agreement with the predictions of our theory.

Nutrient dynamics in two seagrass species, Posidonia coriacea and Zostera tasmanica, on Success Bank, Western Australia

NASA Astrophysics Data System (ADS)

Walker, D. I.; Campey, M. L.; Kendrick, G. A.

2004-06-01

Nutrient concentrations and seasonal differences in atomic ratios (N:P) in plant tissue of Posidonia coriacea Kuo and Cambridge and Zostera tasmanica Aschers (formerly Heterozostera tasmanica (Syst Bot 27 (2002) 468) were measured from multiple locations on Success Bank, southwestern Australia, and used to infer nutritional constraints on seagrass vegetative growth, particularly by phosphorus. Posidonia plant tissue at the west site had higher nitrogen than the east site in both summer and winter. Nitrogen concentrations increased in winter, particularly in sheath tissue, but there was little change in root nitrogen concentrations between sites or seasons. Nitrogen concentrations of leaf tissue were all less than median seagrass values reported by Duarte (Mar Ecol Prog Ser 67 (1990) 201). The seasonality in nutrient concentrations in plant tissues suggests greater nutritional constraints in summer, during periods of high growth. Vegetative growth of Posidonia coriacea was more nutrient limited than that of Zostera tasmanica. Translocation of nutrients along rhizomes to the apex may ensure that growing points are not nutrient limited and that growth can be maintained, and was more apparent in Z. tasmanica than P. coriacea. Sexual reproduction placed large demands on P. coriacea through the high investment of nutrients into fruit, resulting in reduced nutritional constraints on successful seedling recruitment by initially providing seedlings with nutrients.

Pollution Prevention through Peer Education: A Community Health Worker and Small and Home-Based Business Initiative on the Arizona-Sonora Border

PubMed Central

Moreno Ramírez, Denise; Ramírez-Andreotta, Mónica D.; Vea, Lourdes; Estrella-Sánchez, Rocío; Wolf, Ann Marie A.; Kilungo, Aminata; Spitz, Anna H.; Betterton, Eric A.

2015-01-01

Government-led pollution prevention programs tend to focus on large businesses due to their potential to pollute larger quantities, therefore leaving a gap in programs targeting small and home-based businesses. In light of this gap, we set out to determine if a voluntary, peer education approach led by female, Hispanic community health workers (promotoras) can influence small and home-based businesses to implement pollution prevention strategies on-site. This paper describes a partnership between promotoras from a non-profit organization and researchers from a university working together to reach these businesses in a predominately Hispanic area of Tucson, Arizona. From 2008 to 2011, the promotora-led pollution prevention program reached a total of 640 small and home-based businesses. Program activities include technical trainings for promotoras and businesses, generation of culturally and language appropriate educational materials, and face-to-face peer education via multiple on-site visits. To determine the overall effectiveness of the program, surveys were used to measure best practices implemented on-site, perceptions towards pollution prevention, and overall satisfaction with the industry-specific trainings. This paper demonstrates that promotoras can promote the implementation of pollution prevention best practices by Hispanic small and home-based businesses considered “hard-to-reach” by government-led programs. PMID:26371028

Dynamics of TBP binding to the TATA box

NASA Astrophysics Data System (ADS)

Schluesche, Peter; Heiss, Gregor; Meisterernst, Michael; Lamb, Don C.

2008-02-01

Gene expression is highly controlled and regulated in living cells. One of the first steps in gene transcription is recognition of the promoter site by the TATA box Binding Protein (TBP). TBP recruits other transcriptions factors and eventually the RNA polymerase II to transcribe the DNA in mRNA. We developed a single pair Förster Resonance Energy Transfer (spFRET) assay to investigate the mechanism of gene regulation. Here, we apply this assay to investigate the initial binding process of TBP to the adenovirus major late (AdML) promoter site. From the spFRET measurements, we were able to identify two conformations of the TBP-DNA complex that correspond to TBP bound in the correct and the opposite orientation. Increased incubation times or the presence of the transcription factor TFIIA improved the alignment of TBP on the promoter site. Binding of TBP to the TATA box shows a rich dynamics with abrupt transitions between multiple FRET states. A frame-wise histogram analysis revealed the presence of at least six discrete states, showing that TBP binding is more complicated than previously thought. Hence, the spFRET assay is very sensitive to the conformation of the TBP-DNA complex and is very promising tool for investigating the pathway of TBP binding in detail.

Remote sensing of changes in morphology and physiology of trees under stress

NASA Technical Reports Server (NTRS)

Olson, C. E., Jr.; Rohde, W. G.; Ward, J. M.

1970-01-01

Results of continuing studies of forest trees subjected to varying types of stress are reported. Both greenhouse and field studies are included. Greenhouse work with tree seedlings exposed to varying levels of NaCl and CaCl2 in the soil indicated that, in the initial stages, palisade cells shrink and the amount of air space in the leaf increases. As the severity of damage increases, the cells of the spongy mesophyll shrink and flatten, and the amount of air space in the leaf decreases. Statistical analysis of foliar reflectance and associated moisture content data led to a series of regression equations for predicting foliar moisture content from reflectance data. Equations were calculated for three species, yellow birch (Betula alleghaniensis Britton), sugar maple (Acer saccharum Marsh.) and white ash (Fraxinus americana L.) having multiple correlation coefficients of 0.98, 0.94 and 0.93 respectively. Interpretation of multispectral imagery of the Ann Arbor Forestry Test Site (NASA Site 190) provided evidence that infections of Fomes annosus can be detected in the early stages. Infections of two needle cast diseases were also detected in conifer plantations in the test site. A study of automatic interpretation of multispectral scanner imagery for tree species recognition provided encouraging results.

Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

PubMed

Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

2018-01-01

The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Phenology Across the LTER Network: Initial Findings, Future Directions

NASA Astrophysics Data System (ADS)

Henebry, G. M.

2007-12-01

Phenology is, in the words of Aldo Leopold, a "horizontal science" that cuts across and binds together multiple biological disciplines. It is a far-reaching but poorly understood aspect of the environmental sciences. Phenological research has been a component of the Long Term Ecological Research (LTER) Network at several sites over the years. However, it has not received the attention or resources to bring it to the forefront as an effective theme for interdisciplinary and cross-site synthesis. With the recent establishment of the USA National Phenology Network (USA-NPN), it is appropriate to assess the status of phenological knowledge across the LTER Network. A workshop funded by the LTER Network Office took place at the Sevilleta Field Station during February 26 to March 2, 2007. From the workshop three main products emerged: (1) an inventory of LTER phenology datasets, (2) establishment of a website to facilitate information interchange, and (3) a white paper recommending next steps for the LTER Network to engage the USA-NPN. This poster relates the findings and recommendations of the workshop, including a summary of phenologically explicit and phenologically implicit LTER datasets and illustrations of how the climatic envelopes described by simple weather variables can provide context for phenological comparisons within and across sites.

Pollution Prevention through Peer Education: A Community Health Worker and Small and Home-Based Business Initiative on the Arizona-Sonora Border.

PubMed

Ramírez, Denise Moreno; Ramírez-Andreotta, Mónica D; Vea, Lourdes; Estrella-Sánchez, Rocío; Wolf, Ann Marie A; Kilungo, Aminata; Spitz, Anna H; Betterton, Eric A

2015-09-09

Government-led pollution prevention programs tend to focus on large businesses due to their potential to pollute larger quantities, therefore leaving a gap in programs targeting small and home-based businesses. In light of this gap, we set out to determine if a voluntary, peer education approach led by female, Hispanic community health workers (promotoras) can influence small and home-based businesses to implement pollution prevention strategies on-site. This paper describes a partnership between promotoras from a non-profit organization and researchers from a university working together to reach these businesses in a predominately Hispanic area of Tucson, Arizona. From 2008 to 2011, the promotora-led pollution prevention program reached a total of 640 small and home-based businesses. Program activities include technical trainings for promotoras and businesses, generation of culturally and language appropriate educational materials, and face-to-face peer education via multiple on-site visits. To determine the overall effectiveness of the program, surveys were used to measure best practices implemented on-site, perceptions towards pollution prevention, and overall satisfaction with the industry-specific trainings. This paper demonstrates that promotoras can promote the implementation of pollution prevention best practices by Hispanic small and home-based businesses considered "hard-to-reach" by government-led programs.

Immunoglobulin A multiple myeloma with cutaneous involvement in a dog.

PubMed

Mayer, Monique N; Kerr, Moira E; Grier, Candace K; Macdonald, Valerie S

2008-07-01

An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed.

Immunoglobulin A multiple myeloma with cutaneous involvement in a dog

PubMed Central

Mayer, Monique N.; Kerr, Moira E.; Grier, Candace K.; MacDonald, Valerie S.

2008-01-01

An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed. PMID:18827847

Estimating hydraulic properties using a moving-model approach and multiple aquifer tests

USGS Publications Warehouse

Halford, K.J.; Yobbi, D.

2006-01-01

A new method was developed for characterizing geohydrologic columns that extended >600 m deep at sites with as many as six discrete aquifers. This method was applied at 12 sites within the Southwest Florida Water Management District. Sites typically were equipped with multiple production wells, one for each aquifer and one or more observation wells per aquifer. The average hydraulic properties of the aquifers and confining units within radii of 30 to >300 m were characterized at each site. Aquifers were pumped individually and water levels were monitored in stressed and adjacent aquifers during each pumping event. Drawdowns at a site were interpreted using a radial numerical model that extended from land surface to the base of the geohydrologic column and simulated all pumping events. Conceptually, the radial model moves between stress periods and recenters on the production well during each test. Hydraulic conductivity was assumed homogeneous and isotropic within each aquifer and confining unit. Hydraulic property estimates for all of the aquifers and confining units were consistent and reasonable because results from multiple aquifers and pumping events were analyzed simultaneously. Copyright ?? 2005 National Ground Water Association.

Estimating hydraulic properties using a moving-model approach and multiple aquifer tests.

PubMed

Halford, Keith J; Yobbi, Dann

2006-01-01

A new method was developed for characterizing geohydrologic columns that extended >600 m deep at sites with as many as six discrete aquifers. This method was applied at 12 sites within the Southwest Florida Water Management District. Sites typically were equipped with multiple production wells, one for each aquifer and one or more observation wells per aquifer. The average hydraulic properties of the aquifers and confining units within radii of 30 to >300 m were characterized at each site. Aquifers were pumped individually and water levels were monitored in stressed and adjacent aquifers during each pumping event. Drawdowns at a site were interpreted using a radial numerical model that extended from land surface to the base of the geohydrologic column and simulated all pumping events. Conceptually, the radial model moves between stress periods and recenters on the production well during each test. Hydraulic conductivity was assumed homogeneous and isotropic within each aquifer and confining unit. Hydraulic property estimates for all of the aquifers and confining units were consistent and reasonable because results from multiple aquifers and pumping events were analyzed simultaneously.

EPA RE-Powering Mapper Completed Installations

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. Using publically available information, RE-Powering maintains a list of completed renewable energy installations on contaminated sites and landfills. To date, the RE-Powering Initiative has identified 179 renewable energy installations on 171 contaminated lands, landfills, and mine sites, with a cumulative installed capacity of just over 1,124 megawatts (MW) and consistent growth in total installations since the inception of the RE-Powering Initiative. This dataset is current as of April 2016.

An evaluation of two methods for increasing self-initiated verbalizations in autistic children.

PubMed Central

Matson, J L; Sevin, J A; Box, M L; Francis, K L; Sevin, B M

1993-01-01

Three children with autism and mental retardation were treated for deficits in self-initiated speech. A novel treatment package employing visual cue fading was compared with a graduated time-delay procedure previously shown to be effective for increasing self-initiated language. Both treatments included training multiple self-initiated verbalizations using multiple therapists and settings. Both treatments were effective, with no differences in measures of acquisition of target phrases, maintenance of behavioral gains, acquisition with additional therapists and settings, and social validity. PMID:8407687

EPA RE-Powering Mapper Feasibility Studies

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. As part of the RE-Powering America's Land Initiative, the EPA and the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) evaluated the feasibility of developing renewable energy production on Superfund, brownfields, and former landfill or mining sites. These reports pair EPA's expertise on contaminated sites with the renewable energy expertise of NREL.

Airborne net-centric multi-INT sensor control, display, fusion, and exploitation systems

NASA Astrophysics Data System (ADS)

Linne von Berg, Dale C.; Lee, John N.; Kruer, Melvin R.; Duncan, Michael D.; Olchowski, Fred M.; Allman, Eric; Howard, Grant

2004-08-01

The NRL Optical Sciences Division has initiated a multi-year effort to develop and demonstrate an airborne net-centric suite of multi-intelligence (multi-INT) sensors and exploitation systems for real-time target detection and targeting product dissemination. The goal of this Net-centric Multi-Intelligence Fusion Targeting Initiative (NCMIFTI) is to develop an airborne real-time intelligence gathering and targeting system that can be used to detect concealed, camouflaged, and mobile targets. The multi-INT sensor suite will include high-resolution visible/infrared (EO/IR) dual-band cameras, hyperspectral imaging (HSI) sensors in the visible-to-near infrared, short-wave and long-wave infrared (VNIR/SWIR/LWIR) bands, Synthetic Aperture Radar (SAR), electronics intelligence sensors (ELINT), and off-board networked sensors. Other sensors are also being considered for inclusion in the suite to address unique target detection needs. Integrating a suite of multi-INT sensors on a single platform should optimize real-time fusion of the on-board sensor streams, thereby improving the detection probability and reducing the false alarms that occur in reconnaissance systems that use single-sensor types on separate platforms, or that use independent target detection algorithms on multiple sensors. In addition to the integration and fusion of the multi-INT sensors, the effort is establishing an open-systems net-centric architecture that will provide a modular "plug and play" capability for additional sensors and system components and provide distributed connectivity to multiple sites for remote system control and exploitation.

Growth rates of fine aerosol particles at a site near Beijing in June 2013

NASA Astrophysics Data System (ADS)

Zhao, Chuanfeng; Li, Yanan; Zhang, Fang; Sun, Yele; Wang, Pucai

2018-02-01

Growth of fine aerosol particles is investigated during the Aerosol-CCN-Cloud Closure Experiment campaign in June 2013 at an urban site near Beijing. Analyses show a high frequency (˜ 50%) of fine aerosol particle growth events, and show that the growth rates range from 2.1 to 6.5 nm h-1 with a mean value of ˜ 5.1 nm h-1. A review of previous studies indicates that at least four mechanisms can affect the growth of fine aerosol particles: vapor condensation, intramodal coagulation, extramodal coagulation, and multi-phase chemical reaction. At the initial stage of fine aerosol particle growth, condensational growth usually plays a major role and coagulation efficiency generally increases with particle sizes. An overview of previous studies shows higher growth rates over megacity, urban and boreal forest regions than over rural and oceanic regions. This is most likely due to the higher condensational vapor, which can cause strong condensational growth of fine aerosol particles. Associated with these multiple factors of influence, there are large uncertainties for the aerosol particle growth rates, even at the same location.

The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture

PubMed Central

Pai, Athma A; Henriques, Telmo; McCue, Kayla; Burkholder, Adam; Adelman, Karen

2017-01-01

Production of most eukaryotic mRNAs requires splicing of introns from pre-mRNA. The splicing reaction requires definition of splice sites, which are initially recognized in either intron-spanning (‘intron definition’) or exon-spanning (‘exon definition’) pairs. To understand how exon and intron length and splice site recognition mode impact splicing, we measured splicing rates genome-wide in Drosophila, using metabolic labeling/RNA sequencing and new mathematical models to estimate rates. We found that the modal intron length range of 60–70 nt represents a local maximum of splicing rates, but that much longer exon-defined introns are spliced even faster and more accurately. We observed unexpectedly low variation in splicing rates across introns in the same gene, suggesting the presence of gene-level influences, and we identified multiple gene level variables associated with splicing rate. Together our data suggest that developmental and stress response genes may have preferentially evolved exon definition in order to enhance the rate or accuracy of splicing. PMID:29280736

The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture

DOE PAGES

Pai, Athma A.; Henriques, Telmo; McCue, Kayla; ...

2017-12-27

Production of most eukaryotic mRNAs requires splicing of introns from pre-mRNA. The splicing reaction requires definition of splice sites, which are initially recognized in either intron-spanning (‘intron definition’) or exon-spanning (‘exon definition’) pairs. To understand how exon and intron length and splice site recognition mode impact splicing, we measured splicing rates genome-wide in Drosophila, using metabolic labeling/RNA sequencing and new mathematical models to estimate rates. We found that the modal intron length range of 60–70 nt represents a local maximum of splicing rates, but that much longer exon-defined introns are spliced even faster and more accurately. We observed unexpectedly lowmore » variation in splicing rates across introns in the same gene, suggesting the presence of gene-level influences, and we identified multiple gene level variables associated with splicing rate. Together our data suggest that developmental and stress response genes may have preferentially evolved exon definition in order to enhance the rate or accuracy of splicing.« less

The kinetics of pre-mRNA splicing in the Drosophila genome and the influence of gene architecture

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

Pai, Athma A.; Henriques, Telmo; McCue, Kayla

Production of most eukaryotic mRNAs requires splicing of introns from pre-mRNA. The splicing reaction requires definition of splice sites, which are initially recognized in either intron-spanning (‘intron definition’) or exon-spanning (‘exon definition’) pairs. To understand how exon and intron length and splice site recognition mode impact splicing, we measured splicing rates genome-wide in Drosophila, using metabolic labeling/RNA sequencing and new mathematical models to estimate rates. We found that the modal intron length range of 60–70 nt represents a local maximum of splicing rates, but that much longer exon-defined introns are spliced even faster and more accurately. We observed unexpectedly lowmore » variation in splicing rates across introns in the same gene, suggesting the presence of gene-level influences, and we identified multiple gene level variables associated with splicing rate. Together our data suggest that developmental and stress response genes may have preferentially evolved exon definition in order to enhance the rate or accuracy of splicing.« less

Trypsin cleavage of the baculovirus occlusion-derived virus attachment protein P74 is prerequisite in per os infection.

PubMed

Slack, Jeffrey M; Lawrence, Susan D; Krell, Peter J; Arif, Basil M

2008-10-01

Baculovirus occlusion-derived virions (ODVs) contain a number of infectivity factors essential for the initiation of infection in larval midgut cells. Deletion of any of these factors neutralizes infectivity by the per os route. We have observed that P74 of the group I alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is N-terminally cleaved when a soluble form of the protein was incubated with insect midgut tissues under alkaline conditions and that cleavage was prevented by soybean trypsin inhibitor (SBTI). Presently, biological assays were carried out that suggest SBTI inhibits and trypsin enhances baculovirus per os infectivity. We developed a method to rescue per os infectivity of a P74 null virus involving co-transfection of viral DNA with a plasmid that transiently expresses p74. We used this plasmid rescue method to functionally characterize P74. A series of site-directed mutants were generated at the N terminus to evaluate if trypsin cleavage sites were necessary for function. Mutagenesis of R195, R196 and R199 compromised per os infectivity and rendered P74 resistant to midgut trypsin.

Designing Reliable Cohorts of Cardiac Patients across MIMIC and eICU

PubMed Central

Chronaki, Catherine; Shahin, Abdullah; Mark, Roger

2016-01-01

The design of the patient cohort is an essential and fundamental part of any clinical patient study. Knowledge of the Electronic Health Records, underlying Database Management System, and the relevant clinical workflows are central to an effective cohort design. However, with technical, semantic, and organizational interoperability limitations, the database queries associated with a patient cohort may need to be reconfigured in every participating site. i2b2 and SHRINE advance the notion of patient cohorts as first class objects to be shared, aggregated, and recruited for research purposes across clinical sites. This paper reports on initial efforts to assess the integration of Medical Information Mart for Intensive Care (MIMIC) and Philips eICU, two large-scale anonymized intensive care unit (ICU) databases, using standard terminologies, i.e. LOINC, ICD9-CM and SNOMED-CT. Focus of this work is lab and microbiology observations and key demographics for patients with a primary cardiovascular ICD9-CM diagnosis. Results and discussion reflecting on reference core terminology standards, offer insights on efforts to combine detailed intensive care data from multiple ICUs worldwide. PMID:27774488

Structural mechanism of ligand activation in human calcium-sensing receptor

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

Geng, Yong; Mosyak, Lidia; Kurinov, Igor

2016-07-19

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca 2+homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation.more » Our structures reveal multiple binding sites for Ca 2+and PO 4 3-ions. Both ions are crucial for structural integrity of the receptor. While Ca 2+ions stabilize the active state, PO 4 3-ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.« less

Emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care.

PubMed

Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih; De Libero, Gennaro; Singhal, Amit; Demirci, Utkan

2014-11-30

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care. Copyright © 2014 Elsevier B.V. All rights reserved.

Emerging Technologies for Monitoring Drug-Resistant Tuberculosis at the Point-of-Care

PubMed Central

Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih; De Libero, Gennaro; Singhal, Amit; Demirci, Utkan

2014-01-01

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and at least one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care. PMID:24882226

40 CFR 63.6612 - By what date must I conduct the initial performance tests or other initial compliance...

Code of Federal Regulations, 2011 CFR

2011-07-01

... stationary RICE with a site rating of less than or equal to 500 brake HP located at a major source of HAP emissions or an existing stationary RICE located at an area source of HAP emissions? 63.6612 Section 63.6612... other initial compliance demonstrations if I own or operate an existing stationary RICE with a site...

40 CFR 63.6612 - By what date must I conduct the initial performance tests or other initial compliance...

Code of Federal Regulations, 2010 CFR

2010-07-01

... stationary RICE with a site rating of less than or equal to 500 brake HP located at a major source of HAP emissions or an existing stationary RICE located at an area source of HAP emissions? 63.6612 Section 63.6612... other initial compliance demonstrations if I own or operate an existing stationary RICE with a site...

Single-site labeling of lysine in proteins through a metal-free multicomponent approach.

PubMed

Chilamari, Maheshwerreddy; Kalra, Neetu; Shukla, Sanjeev; Rai, Vishal

2018-06-15

We report a chemoselective and site-selective approach that distinguishes one Lys from its multiple copies, N-terminus, and other competitors. The phospha-Mannich protocol works with multiple proteins and installs probes without structural and functional perturbations. It delivers an antibody-drug conjugate with selective anti-proliferative activity towards HER2 expressing SKBR3 breast cancer cells.

A methodology for evaluating organizational change in community-based chronic disease interventions.

PubMed

Hanni, Krista D; Mendoza, Elsa; Snider, John; Winkleby, Marilyn A

2007-10-01

In 2003, the Monterey County Health Department, serving Salinas, California, was awarded one of 12 grants from the Steps to a HealthierUS Program to implement a 5-year, multiple-intervention community approach to reduce diabetes, asthma, and obesity. National adult and youth surveys to assess long-term outcomes are required by all Steps sites; however, site-specific surveys to assess intermediate outcomes are not required. Salinas is a medically underserved community of primarily Mexican American residents with high obesity rates and other poor health outcomes. The health department's Steps program has partnered with traditional organizations such as schools, senior centers, clinics, and faith-based organizations as well as novel organizations such as employers of agricultural workers and owners of taquerias. The health department and the Stanford Prevention Research Center developed new site-specific, community-focused partner surveys to assess intermediate outcomes to augment the nationally mandated surveys. These site-specific surveys will evaluate changes in organizational practices, policies, or both following the socioecological model, specifically the Spectrum of Prevention. Our site-specific partner surveys helped to 1) identify promising new partners, select initial partners from neighborhoods with the greatest financial need, and identify potentially successful community approaches; and 2) provide data for evaluating intermediate outcomes matched to national long-term outcomes so that policy and organizational level changes could be assessed. These quantitative surveys also provide important context-specific qualitative data, identifying opportunities for strengthening community partnerships. Developing site-specific partner surveys in multisite intervention studies can provide important data to guide local program efforts and assess progress toward intermediate outcomes matched to long-term outcomes from nationally mandated surveys.

Pathways to Medical Home Recognition: A Qualitative Comparative Analysis of the PCMH Transformation Process.

PubMed

Mendel, Peter; Chen, Emily K; Green, Harold D; Armstrong, Courtney; Timbie, Justin W; Kress, Amii M; Friedberg, Mark W; Kahn, Katherine L

2017-12-15

To understand the process of practice transformation by identifying pathways for attaining patient-centered medical home (PCMH) recognition. The CMS Federally Qualified Health Center (FQHC) Advanced Primary Care Practice Demonstration was designed to help FQHCs achieve NCQA Level 3 PCMH recognition and improve patient outcomes. We used a stratified random sample of 20 (out of 503) participating sites for this analysis. We developed a conceptual model of structural, cultural, and implementation factors affecting PCMH transformation based on literature and initial qualitative interview themes. We then used conventional cross-case analysis, followed by qualitative comparative analysis (QCA), a cross-case method based on Boolean logic algorithms, to systematically identify pathways (i.e., combinations of factors) associated with attaining-or not attaining-Level 3 recognition. Site-level indicators were derived from semistructured interviews with site leaders at two points in time (mid- and late-implementation) and administrative data collected prior to and during the demonstration period. The QCA results identified five distinct pathways to attaining PCMH recognition and four distinct pathways to not attaining recognition by the end of the demonstration. Across these pathways, one condition (change leader capacity) was common to all pathways for attaining recognition, and another (previous improvement or recognition experience) was absent in all pathways for not attaining recognition. In general, sites could compensate for deficiencies in one factor with capacity in others, but they needed a threshold of strengths in cultural and implementation factors to attain PCMH recognition. Future efforts at primary care transformation should take into account multiple pathways sites may pursue. Sites should be assessed on key cultural and implementation factors, in addition to structural components, in order to differentiate interventions and technical assistance. © Health Research and Educational Trust.

Martian Dune Ripples as Indicators of Recent Surface Wind Patterns

NASA Astrophysics Data System (ADS)

Johnson, M.; Zimbelman, J. R.

2015-12-01

Sand dunes have been shown to preserve the most recent wind patterns in their ripple formations. This investigation continues the manual documentation of ripples on Martian dunes in order to assess surface wind flow. Study sites investigated must have clear HiRISE frames and be able to represent diverse locations across the surface, decided primarily by their spread of latitude and longitude values. Additionally, frames with stereo pairs are preferred because of their ability to create digital terrain models. This will assist in efforts to relate dune slopes and obstacles to ripple patterns. The search and analysis period resulted in 40 study sites with mapped ripples. Lines were drawn perpendicular to ripple crests across three adjacent ripples in order to document both ripple wavelength from line length and inferred wind direction from azimuth. It is not possible to infer a unique wind direction from ripple orientation alone and therefore these inferred directions have a 180 degree ambiguity. Initial results from all study sites support previous observations that the Martian surface has many dune types in areas with adequate sand supply. The complexity of ripple patterns varies greatly across sites as well as within individual sites. Some areas of uniform directionality for hundreds of kilometers suggest a unimodal wind regime while overlapping patterns suggest multiple dominant winds or seasonally varying winds. In most areas, form flow related to dune shape seems to have a large effect on orientation and must be considered along with the dune type. As long as the few steep slip faces on these small dunes are avoided, form flow can be considered the dominant cause of deviation from the regional wind direction. Regional results, wind roses, and comparisons to previous work will be presented for individual sites.

Unifying screening processes within the PROSPR consortium: a conceptual model for breast, cervical, and colorectal cancer screening.

PubMed

Beaber, Elisabeth F; Kim, Jane J; Schapira, Marilyn M; Tosteson, Anna N A; Zauber, Ann G; Geiger, Ann M; Kamineni, Aruna; Weaver, Donald L; Tiro, Jasmin A

2015-06-01

General frameworks of the cancer screening process are available, but none directly compare the process in detail across different organ sites. This limits the ability of medical and public health professionals to develop and evaluate coordinated screening programs that apply resources and population management strategies available for one cancer site to other sites. We present a trans-organ conceptual model that incorporates a single screening episode for breast, cervical, and colorectal cancers into a unified framework based on clinical guidelines and protocols; the model concepts could be expanded to other organ sites. The model covers four types of care in the screening process: risk assessment, detection, diagnosis, and treatment. Interfaces between different provider teams (eg, primary care and specialty care), including communication and transfer of responsibility, may occur when transitioning between types of care. Our model highlights across each organ site similarities and differences in steps, interfaces, and transitions in the screening process and documents the conclusion of a screening episode. This model was developed within the National Cancer Institute-funded consortium Population-based Research Optimizing Screening through Personalized Regimens (PROSPR). PROSPR aims to optimize the screening process for breast, cervical, and colorectal cancer and includes seven research centers and a statistical coordinating center. Given current health care reform initiatives in the United States, this conceptual model can facilitate the development of comprehensive quality metrics for cancer screening and promote trans-organ comparative cancer screening research. PROSPR findings will support the design of interventions that improve screening outcomes across multiple cancer sites. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Unravelling the Mysteries of Slip Histories, Validating Cosmogenic 36Cl Derived Slip Rates on Normal Faults

NASA Astrophysics Data System (ADS)

Goodall, H.; Gregory, L. C.; Wedmore, L.; Roberts, G.; Shanks, R. P.; McCaffrey, K. J. W.; Amey, R.; Hooper, A. J.

2017-12-01

The cosmogenic isotope chlorine-36 (36Cl) is increasingly used as a tool to investigate normal fault slip rates over the last 10-20 thousand years. These slip histories are being used to address complex questions, including investigating slip clustering and understanding local and large scale fault interaction. Measurements are time consuming and expensive, and as a result there has been little work done validating these 36Cl derived slip histories. This study aims to investigate if the results are repeatable and therefore reliable estimates of how normal faults have been moving in the past. Our approach is to test if slip histories derived from 36Cl are the same when measured at different points along the same fault. As normal fault planes are progressively exhumed from the surface they accumulate 36Cl. Modelling these 36Cl concentrations allows estimation of a slip history. In a previous study, samples were collected from four sites on the Magnola fault in the Italian Apennines. Remodelling of the 36Cl data using a Bayesian approach shows that the sites produced disparate slip histories, which we interpret as being due to variable site geomorphology. In this study, multiple sites have been sampled along the Campo Felice fault in the central Italian Apennines. Initial results show strong agreement between the sites we have processed so far and a previous study. This indicates that if sample sites are selected taking the geomorphology into account, then 36Cl derived slip histories will be highly similar when sampled at any point along the fault. Therefore our study suggests that 36Cl derived slip histories are a consistent record of fault activity in the past.

A knowledge translation tool improved osteoporosis disease management in primary care: an interrupted time series analysis.

PubMed

Kastner, Monika; Sawka, Anna M; Hamid, Jemila; Chen, Maggie; Thorpe, Kevin; Chignell, Mark; Ewusie, Joycelyne; Marquez, Christine; Newton, David; Straus, Sharon E

2014-09-25

Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems, yet gaps in management still exist. In response, we developed a multi-component osteoporosis knowledge translation (Op-KT) tool involving a patient-initiated risk assessment questionnaire (RAQ), which generates individualized best practice recommendations for physicians and customized education for patients at the point of care. The objective of this study was to evaluate the effectiveness of the Op-KT tool for appropriate disease management by physicians. The Op-KT tool was evaluated using an interrupted time series design. This involved multiple assessments of the outcomes 12 months before (baseline) and 12 months after tool implementation (52 data points in total). Inclusion criteria were family physicians and their patients at risk for osteoporosis (women aged ≥ 50 years, men aged ≥ 65 years). Primary outcomes were the initiation of appropriate osteoporosis screening and treatment. Analyses included segmented linear regression modeling and analysis of variance. The Op-KT tool was implemented in three family practices in Ontario, Canada representing 5 family physicians with 2840 age eligible patients (mean age 67 years; 76% women). Time series regression models showed an overall increase from baseline in the initiation of screening (3.4%; P < 0.001), any osteoporosis medications (0.5%; P = 0.006), and calcium or vitamin D (1.2%; P = 0.001). Improvements were also observed at site level for all the three sites considered, but these results varied across the sites. Of 351 patients who completed the RAQ unprompted (mean age 64 years, 77% women), the mean time for completing the RAQ was 3.43 minutes, and 56% had any disease management addressed by their physician. Study limitations included the inherent susceptibility of our design compared with a randomized trial. The multicomponent Op-KT tool significantly increased osteoporosis investigations in three family practices, and highlights its potential to facilitate patient self-management. Next steps include wider implementation and evaluation of the tool in primary care.

Analysis in Motion Initiative – Summarization Capability

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

Arendt, Dustin; Pirrung, Meg; Jasper, Rob

2017-06-22

Analysts are tasked with integrating information from multiple data sources for important and timely decision making. What if sense making and overall situation awareness could be improved through visualization techniques? The Analysis in Motion initiative is advancing the ability to summarize and abstract multiple streams and static data sources over time.

Impact of 18F-fluorodeoxyglucose positron emission tomography before and after definitive radiation therapy in patients with apparently solitary plasmacytoma.

PubMed

Kim, Paul J; Hicks, Rodney J; Wirth, Andrew; Ryan, Gail; Seymour, John F; Prince, H Miles; Mac Manus, Michael P

2009-07-01

To evaluate the impact of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) on management of patients with apparently isolated plasmacytoma. Twenty-one patients with apparently solitary plasmacytoma who underwent FDG-PET for staging or restaging were identified from a central PET database. They were either candidates for or had received definitive radiation therapy (RT). Seventeen patients had initial staging scans for bone (n = 11) or soft tissue (n = 6) plasmacytomas, and 11 had PET scans after RT. Only 1 of 14 known untreated sites of plasmacytoma was not identified on staging PET (lesion sensitivity = 93%). Three plasmacytomas were excised before PET. Staging PET influenced management in 6 of 17 patients (35%) by showing multiple myeloma (n = 1), discouraging RT after complete resection (n = 1), excluding plasmacytoma at a second site (n = 1), by increasing RT fields (n = 2), or by suggesting sarcoidosis (n = 1). Fifteen of 17 patients with initial staging PET scans received definitive RT. Restaging PET scans after RT showed complete metabolic response in 8 of 11 cases and progressive disease in 2. Two patients with either no response or partial metabolic response had late responses. Staging sestamibi and PET scans were concordant in five of six occasions (one sestamibi scan was false negative). FDG-PET has value for staging and RT planning in plasmacytoma and potentially could have a role in response-assessment after RT. Slow resolution of FDG uptake posttreatment does not necessarily imply an adverse prognosis.

The ADIPS pilot National Diabetes in Pregnancy Audit Project.

PubMed

Simmons, David; Cheung, N Wah; McIntyre, H David; Flack, Jeff R; Lagstrom, Janet; Bond, Dianne; Johnson, Elizabeth; Wolmarans, Louise; Wein, Peter; Sinha, Ashim K

2007-06-01

Limited resources are available to compare outcomes of pregnancies complicated by diabetes across different centres. To compare the use of paper, stand alone and networked electronic processes for a sustainable, systematic international audit of diabetes in pregnancy care. Development of diabetes in pregnancy minimum dataset using nominal group technique, email user survey of difficulties with audit tools and collation of audit data from nine pilot sites across Australia and New Zealand. Seventy-nine defined data items were collected: 33 were for all women, nine for those with gestational diabetes (GDM) and 37 for women with pregestational diabetes. After the pilot, four new fields were requested and 18 fields had queries regarding utility or definition. A range of obstacles hampered the implementation of the audit including Medical Records Committee processes, other medical/non-medical staff not initially involved, temporary staff, multiple clinical records used by different parts of the health service, difficulty obtaining the postnatal test results and time constraints. Implementation of electronic audits in both the networked and the stand-alone settings had additional problems relating to the need to nest within pre-existing systems. Among the 496 women (45 type 1; 43 type 2; 399 GDM) across the nine centres, there were substantial differences in key quality and outcome indicators between sites. We conclude that an international, multicentre audit and benchmarking program is feasible and sustainable, but can be hampered by pre-existing processes, particularly in the initial introduction of electronic methods.

Multisite Light-Induced Phosphorylation of the Transcription Factor PIF3 Is Necessary for Both Its Rapid Degradation and Concomitant Negative Feedback Modulation of Photoreceptor phyB Levels in Arabidopsis[C][W

PubMed Central

Ni, Weimin; Xu, Shou-Ling; Chalkley, Robert J.; Pham, Thao Nguyen D.; Guan, Shenheng; Maltby, Dave A.; Burlingame, Alma L.; Wang, Zhi-Yong; Quail, Peter H.

2013-01-01

Plants constantly monitor informational light signals using sensory photoreceptors, which include the phytochrome (phy) family (phyA to phyE), and adjust their growth and development accordingly. Following light-induced nuclear translocation, photoactivated phy molecules bind to and induce rapid phosphorylation and degradation of phy-interacting basic Helix Loop Helix (bHLH) transcription factors (PIFs), such as PIF3, thereby regulating the expression of target genes. However, the mechanisms underlying the signal-relay process are still not fully understood. Here, using mass spectrometry, we identify multiple, in vivo, light-induced Ser/Thr phosphorylation sites in PIF3. Using transgenic expression of site-directed mutants of PIF3, we provide evidence that a set of these phosphorylation events acts collectively to trigger rapid degradation of the PIF3 protein in response to initial exposure of dark-grown seedlings to light. In addition, we show that phyB-induced PIF3 phosphorylation is also required for the known negative feedback modulation of phyB levels in prolonged light, potentially through codegradation of phyB and PIF3. This mutually regulatory intermolecular transaction thus provides a mechanism with the dual capacity to promote early, graded, or threshold regulation of the primary, PIF3-controlled transcriptional network in response to initial light exposure, and later, to attenuate global sensitivity to the light signal through reductions in photoreceptor levels upon prolonged exposure. PMID:23903316

[Impact of volatile sulphur compounds in periodontal pockets on initial periodontal therapy].

PubMed

Li, Xiao-Jun; Dong, Ling-Ling; Kong, Jing-Jia

2008-07-01

To investigate the relationship of volatile sulphur compounds((VSC)levels in periodontal pockets with severity of periodontitis, and the impact of VSC on the result of initial periodontal therapy. Twenty-five patients with chronic periodontitis(CP)(13 males and 12 females with average age of 35) were included in this study. Clinical periodontal parameters, plaque index, probing depth(PD), attachment loss(AL), and bleeding on probing(BOP) were recorded before and 3 months after the initial therapy. VSC levels were measured with a portable monitor in a digital score ranging from 0.0 to 5.0. All of 5 054 sites for 840 teeth were included in this study. Before treatment the percentage of VSC-positive sites was 17.1%, 52.3% and 86.0% for shallow (PD<3 mm), moderate(PD 4-6 mm) and deep (PD>7 mm) pocket, respectively (P<0.001). In most VSC-positive sites the VSC levels were<1.0. Percentage of sites with a high VSC levels was significantly different among three groups (P<0.01). All clinical parameters in VSC-negative sites were reduced significantly following the initial therapy. The reduction of PD and AL in VSC-positive sites by treatment was less marked than that in VSC-negative sites. VSC in periodontal pockets may be a potential indicator for detecting severity of CP and a useful predictor for therapeutic success.

A standardized online clinical education and assessment tool for neurology clerkship students assigned to multiple sites.

PubMed

Holland, Neil R; Grinberg, Ilya; Tabby, David

2014-01-01

The Drexel neurology clerkship experience can vary from large groups at a university hospital inpatient unit to smaller groups at private physician offices. Evaluations are based on the site director's subjective assessment and performance on the National Board of Medical Examiners neurology shelf examination. We are developing a standardized online clinical neurology course and quiz for the whole clerkship. We piloted the course and quiz at a single site for one academic year and compared their test scores with a control group of students at other clerkship sites who took the online quiz without viewing the course. Students at the pilot site achieved higher scores both on the neurology shelf examination and the clinical quiz and also reported higher teaching satisfaction scores than students at all other sites. There was a 97 % participation rate in the online quiz from the other sites. Use of this online course and quiz provides effective standardized clinical neurology teaching and evaluation that can be applied to students across multiple sites.

External Validity in Policy Evaluations That Choose Sites Purposively

ERIC Educational Resources Information Center

Olsen, Robert B.; Orr, Larry L.; Bell, Stephen H.; Stuart, Elizabeth A.

2013-01-01

Evaluations of the impact of social programs are often carried out in multiple sites, such as school districts, housing authorities, local TANF offices, or One-Stop Career Centers. Most evaluations select sites purposively following a process that is nonrandom. Unfortunately, purposive site selection can produce a sample of sites that is not…

Informative graphing of continuous safety variables relative to normal reference limits.

PubMed

Breder, Christopher D

2018-05-16

Interpreting graphs of continuous safety variables can be complicated because differences in age, gender, and testing site methodologies data may give rise to multiple reference limits. Furthermore, data below the lower limit of normal are compressed relative to those points above the upper limit of normal. The objective of this study is to develop a graphing technique that addresses these issues and is visually intuitive. A mock dataset with multiple reference ranges is initially used to develop the graphing technique. Formulas are developed for conditions where data are above the upper limit of normal, normal, below the lower limit of normal, and below the lower limit of normal when the data value equals zero. After the formulae are developed, an anonymized dataset from an actual set of trials for an approved drug is evaluated comparing the technique developed in this study to standard graphical methods. Formulas are derived for the novel graphing method based on multiples of the normal limits. The formula for values scaled between the upper and lower limits of normal is a novel application of a readily available scaling formula. The formula for the lower limit of normal is novel and addresses the issue of this value potentially being indeterminate when the result to be scaled as a multiple is zero. The formulae and graphing method described in this study provides a visually intuitive method to graph continuous safety data including laboratory values, vital sign data.

Geologic, hydrologic, and water-quality data from multiple-well monitoring sites in the Central and West Coast basins, Los Angeles County, California, 1995-2000

USGS Publications Warehouse

Land, Michael; Everett, R.R.; Crawford, S.M.

2002-01-01

In 1995, the U.S. Geological Survey (USGS), in cooperation with the HYPERLINK 'http://wrd.org' Water Replenishment District of Southern California (WRDSC), began a study to examine ground-water resources in the Central and West Coast Basins in Los Angeles County, California. The study characterizes the geohydrology and geochemistry of the regional ground-water flow system and provides extensive data for evaluating ground-water management issues. This report is a compilation of geologic, hydrologic, and water-quality data collected from 24 recently constructed multiple-well monitoring sites for the period 1995?2000. Descriptions of the collected drill cuttings were compiled into lithologic logs, which are summarized along with geophysical logs?including gamma-ray, spontaneous potential, resistivity, electromagnetic induction, and temperature tool logs?for each monitoring site. At selected sites, cores were analyzed for magnetic orientation, physical and thermal properties, and mineralogy. Field and laboratory estimates of hydraulic conductivity are presented for most multiple-well monitoring sites. Periodic water-level measurements are also reported. Water-quality information for major ions, nutrients, trace elements, deuterium and oxygen-18, and tritium is presented for the multiple-well monitoring locations, and for selected existing production and observation wells. In addition, boron-11, carbon-13, carbon-14, sulfur-34, and strontium-87/86 data are presented for selected wells.

Integrated multiple patch-clamp array chip via lateral cell trapping junctions

NASA Astrophysics Data System (ADS)

Seo, J.; Ionescu-Zanetti, C.; Diamond, J.; Lal, R.; Lee, L. P.

2004-03-01

We present an integrated multiple patch-clamp array chip by utilizing lateral cell trapping junctions. The intersectional design of a microfluidic network provides multiple cell addressing and manipulation sites for efficient electrophysiological measurements at a number of patch sites. The patch pores consist of openings in the sidewall of a main fluidic channel, and a membrane patch is drawn into a smaller horizontal channel. This device geometry not only minimizes capacitive coupling between the cell reservoir and the patch channel, but also allows simultaneous optical and electrical measurements of ion channel proteins. Evidence of the hydrodynamic placement of mammalian cells at the patch sites as well as measurements of patch sealing resistance is presented. Device fabrication is based on micromolding of polydimethylsiloxane, thus allowing inexpensive mass production of disposable high-throughput biochips.

Feasibility Study of Economics and Performance of Biomass Power Generation at the Former Farmland Industries Site in Lawrence, Kansas. A Study Prepared in Partnership with the Environmental Protection Agency for the RE-Powering America's Land Initiative: Siting Renewable Energy on Potentially Contaminated Land and Mine Sites

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

Tomberlin, G.; Mosey, G.

2013-03-01

Under the RE-Powering America's Land initiative, the U.S. Environmental Protection Agency (EPA) provided funding to the National Renewable Energy Laboratory (NREL) to support a feasibility study of biomass renewable energy generation at the former Farmland Industries site in Lawrence, Kansas. Feasibility assessment team members conducted a site assessment to gather information integral to this feasibility study. Information such as biomass resources, transmission availability, on-site uses for heat and power, community acceptance, and ground conditions were considered.

"None of the above" as a correct and incorrect alternative on a multiple-choice test: implications for the testing effect.

PubMed

Odegard, Timothy N; Koen, Joshua D

2007-11-01

Both positive and negative testing effects have been demonstrated with a variety of materials and paradigms (Roediger & Karpicke, 2006b). The present series of experiments replicate and extend the research of Roediger and Marsh (2005) with the addition of a "none-of-the-above" response option. Participants (n=32 in both experiments) read a set of passages, took an initial multiple-choice test, completed a filler task, and then completed a final cued-recall test (Experiment 1) or multiple-choice test (Experiment 2). Questions were manipulated on the initial multiple-choice test by adding a "none-of-the-above" response alternative (choice "E") that was incorrect ("E" Incorrect) or correct ("E" Correct). The results from both experiments demonstrated that the positive testing effect was negated when the "none-of-the-above" alternative was the correct response on the initial multiple-choice test, but was still present when the "none-of-the-above" alternative was an incorrect response.

A Non-Canonical Initiation Site Is Required for Efficient Translation of the Dendritically Localized Shank1 mRNA

PubMed Central

Studtmann, Katrin; Ölschläger-Schütt, Janin; Buck, Friedrich; Richter, Dietmar; Sala, Carlo; Bockmann, Jürgen; Kindler, Stefan; Kreienkamp, Hans-Jürgen

2014-01-01

Local protein synthesis in dendrites enables neurons to selectively change the protein complement of individual postsynaptic sites. Though it is generally assumed that this mechanism requires tight translational control of dendritically transported mRNAs, it is unclear how translation of dendritic mRNAs is regulated. We have analyzed here translational control elements of the dendritically localized mRNA coding for the postsynaptic scaffold protein Shank1. In its 5′ region, the human Shank1 mRNA exhibits two alternative translation initiation sites (AUG+1 and AUG+214), three canonical upstream open reading frames (uORFs1-3) and a high GC content. In reporter assays, fragments of the 5′UTR with high GC content inhibit translation, suggesting a contribution of secondary structures. uORF3 is most relevant to translation control as it overlaps with the first in frame start codon (AUG+1), directing translation initiation to the second in frame start codon (AUG+214). Surprisingly, our analysis points to an additional uORF initiated at a non-canonical ACG start codon. Mutation of this start site leads to an almost complete loss of translation initiation at AUG+1, demonstrating that this unconventional uORF is required for Shank1 synthesis. Our data identify a novel mechanism whereby initiation at a non-canonical site allows for translation of the main Shank1 ORF despite a highly structured 5′UTR. PMID:24533096

Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

PubMed

Eickenscheidt, Max; Zeck, Günther

2014-06-01

The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

Intraoperative mapping during repeat awake craniotomy reveals the functional plasticity of adult cortex.

PubMed

Southwell, Derek G; Hervey-Jumper, Shawn L; Perry, David W; Berger, Mitchel S

2016-05-01

OBJECT To avoid iatrogenic injury during the removal of intrinsic cerebral neoplasms such as gliomas, direct electrical stimulation (DES) is used to identify cortical and subcortical white matter pathways critical for language, motor, and sensory function. When a patient undergoes more than 1 brain tumor resection as in the case of tumor recurrence, the use of DES provides an unusual opportunity to examine brain plasticity in the setting of neurological disease. METHODS The authors examined 561 consecutive cases in which patients underwent DES mapping during surgery forglioma resection. "Positive" and "negative" sites-discrete cortical regions where electrical stimulation did (positive) or did not (negative) produce transient sensory, motor, or language disturbance-were identified prior to tumor resection and documented by intraoperative photography for categorization into functional maps. In this group of 561 patients, 18 were identified who underwent repeat surgery in which 1 or more stimulation sites overlapped with those tested during the initial surgery. The authors compared intraoperative sensory, motor, or language mapping results between initial and repeat surgeries, and evaluated the clinical outcomes for these patients. RESULTS A total of 117 sites were tested for sensory (7 sites, 6.0%), motor (9 sites, 7.7%), or language (101 sites, 86.3%) function during both initial and repeat surgeries. The mean interval between surgical procedures was 4.1 years. During initial surgeries, 95 (81.2%) of 117 sites were found to be negative and 22 (18.8%) of 117 sites were found to be positive. During repeat surgeries, 103 (88.0%) of 117 sites were negative and 14 (12.0%) of 117 were positive. Of the 95 sites that were negative at the initial surgery, 94 (98.9%) were also negative at the repeat surgery, while 1 (1.1%) site was found to be positive. Of the 22 sites that were initially positive, 13 (59.1%) remained positive at repeat surgery, while 9 (40.9%) had become negative for function. Overall, 6 (33.3%) of 18 patients exhibited loss of function at 1 or more motor or language sites between surgeries. Loss of function at these sites was not associated with neurological impairment at the time of repeat surgery, suggesting that neurological function was preserved through neural circuit reorganization or activation of latent functional pathways. CONCLUSIONS The adult central nervous system reorganizes motor and language areas in patients with glioma. Ultimately, adult neural plasticity may help to preserve motor and language function in the presence of evolving structural lesions. The insight gained from this subset of patients has implications for our understanding of brain plasticity in clinical settings.

Opportunities and Strategies for Testing and Infusion of ISRU in the Evolvable Mars Campaign

NASA Technical Reports Server (NTRS)

Mueller, Robert P.; Sibille, Laurent; Mantovani, James; Sanders, Gerald B.; Jones, Christopher A.

2015-01-01

HE Evolvable Mars Campaign (EMC) is developing the plans and systems needed for a robust, evolutionary strategy to explore cis-lunar space, the Mars sphere of influence (including the moons of Mars), and the surface of Mars. Recently, the emphasis of NASA's plans has changed to focus on the prolonged pioneering of space, rather than focusing on a single crewed mission as the ultimate goal. A sustainable, pioneering vision of space would include in-situ resource utilization (ISRU) in multiple forms and at multiple destinations: atmospheric capture of Mars CO2 and/or volatiles for consumables and propellants, regolith for bulk and refined materials, and in-situ manufacturing at the Moon, Mars, and other bodies. These resources would enable a reduction in the logistical needs from Earth for future missions, thus preparing the way for a sustained presence on Mars. Although the EMC initially relies only on propellant production for the Mars ascent vehicle via ISRU, one of its primary objectives is to prospect at every EMC destination to understand the potential for ISRU; this will permit true pioneering to be enabled after the first crew arrives at Mars. Recent and ongoing analysis has considered the possible prospecting measurements that can be performed at the asteroid returned to cis-lunar space by the Asteroid Robotic Redirect Mission (ARRM), at the lunar surface, at Phobos and Deimos, and on the surface of Mars to identify available resources for future use. These opportunities will be available on missions currently in the Evolvable Mars Campaign construct, and will also facilitate the testing and demonstration of resource acquisition, processing, storage, and useage technologies that can play a role in later missions. This analysis has also led to the identification of several objectives that should be targeted during the missions building up to and including the initial crewed missions. These objectives are mapped to strategies for incorporating ISRU to support resource cycle closure and reduce mass requirements from Earth. This analysis has yielded engineering constraints, based on ISRU, that impact the evaluation of landing sites for missions to the surface of Mars. The terrain of a particular site must be sufficiently flat to permit ISRU systems, as well as ancillary systems such as power and propellant storage tanks, to be landed, moved into position, set up, and operated. Water must be accessible in a form that can be acquired via ISRU, in quantities that align with demands. The chosen method of acquiring and processing water should align with the available resources at a particular site, and that site must have sufficient quantities to meet the requirements (based on crew consumables and propellant demands). Lower altitude landing sites are preferred, as the increase in density can facilitate carbon dioxide acquisition from the atmosphere. Another preference is for sites with a greater ability to move regolith for civil engineering purposes; for example, this would be conducive to both bulk regolith uses (such as the manufacture of berms), and processed regolith uses (such as microwave sintering).

Mars Surface System Common Capabilities and Challenges for Human Missions

NASA Technical Reports Server (NTRS)

Hoffman, Stephen J.; Toups, Larry

2016-01-01

NASA has begun a process to identify and evaluate candidate locations where humans could land, live and work on the martian surface. These locations are referred to as Exploration Zones (EZs). Given current mission concepts, an EZ is a collection of Regions of Interest (ROIs) that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains a landing site and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. In parallel with this process, NASA continues to make progress on the Evolvable Mars Campaign examining alternatives that can pioneer an extended human presence on Mars that is Earth independent. This involves ongoing assessments of surface systems and operations to enable a permanent, sustainable human presence. Because of the difficulty in getting equipment and supplies to the surface of Mars, part of these assessments involve identifying those systems and processes that can perform in multiple, sometimes completely unrelated, situations. These assessments have been performed in a very generic surface mission carried out at a very generic surface location. As specific candidate EZs are identified it becomes important to evaluate the current suite of surface systems and operations as they are likely to perform for the specific locations and for the types of operations - both scientific and development - that are proposed for these EZs. It is also important to evaluate the proposed EZs for their suitability to be explored or developed given the range of capabilities and constraints for the types of surface systems and operations being considered within the EMC. This means looking at setting up and operating a field station at a central location within the EZ as well as traversing to and exploring the scientific ROIs within the boundaries of the EZ. The proposed paper will describe the current status of common systems and operations as they can be applied to actual EZ locations on Mars. Initially these EZs will be the four locations identified MEPAG's Human Exploration of Mars Science Analysis Group (HEM-SAG) that will be used as representative of the EZs that will emerge from the process that NASA has initiated. An example process that could be commonly applied is an approach for developing a field station site plan that would be demonstrated by applying this process to each of the four HEM-SAG sites. Examples of common systems include (a) mobility systems that can be used to off-load and move payloads to specific locations at the central field station location that could also be used to traverse long distances to reach some of the more remote ROIs or (b) robotic systems that can support various activities (such as system set up and maintenance) at the field station that could also be used to explore scientific ROIs and used to support site-specific ISRU production activities.

40 CFR 63.6611 - By what date must I conduct the initial performance tests or other initial compliance...

Code of Federal Regulations, 2011 CFR

2011-07-01

... reconstructed 4SLB SI stationary RICE with a site rating of greater than or equal to 250 and less than or equal... compliance demonstrations if I own or operate a new or reconstructed 4SLB SI stationary RICE with a site... of HAP emissions? If you own or operate a new or reconstructed 4SLB stationary RICE with a site...

Safinamide.

PubMed

Fariello, Ruggero G

2007-01-01

Safinamide (SAF) ((S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino)propanamide) was initially synthetized by Farmitalia Carlo Erba (Italy). Following initial anticonvulsant screening, safinamide was selected for its potency, broad spectrum of action, and good safety margin. Pharmacodynamic properties probably relevant to its antiepileptic activity are use- and frequency-dependent block of voltage sensitive Na+ channels, block of Ca++ channels, and glutamate release inhibition. Possibly contributing mechanism are also selective and reversible monoamide oxidase B inhibition and dopamine and noradrenaline uptake inhibition. The high selectivity for the sigma-1 receptor site does not entail psychotomimetic or behavioral changes. In several experimental in vitro and in vivo conditions, SAF exerts neurorescuing and neuroprotectant effects. Safinamide is water soluble and suitable for 1 times a day oral administration in humans. In a pilot phase II study in 38 refractory epilepsy patients affected by multiple types of seizures, 41% of subjects obtained > or =50% seizure reduction during a 12-week escalating dose up to 300 mg 1 times day compared with perspective baseline. Safinamide is being developed in phase III for treatment of Parkinson's disease, whereas the development in epilepsy relates to the industrial strategy of the company.

Three-dimensional reconstruction of rat knee joint using episcopic fluorescence image capture.

PubMed

Takaishi, R; Aoyama, T; Zhang, X; Higuchi, S; Yamada, S; Takakuwa, T

2014-10-01

Development of the knee joint was morphologically investigated, and the process of cavitation was analyzed by using episcopic fluorescence image capture (EFIC) to create spatial and temporal three-dimensional (3D) reconstructions. Knee joints of Wister rat embryos between embryonic day (E)14 and E20 were investigated. Samples were sectioned and visualized using an EFIC. Then, two-dimensional image stacks were reconstructed using OsiriX software, and 3D reconstructions were generated using Amira software. Cavitations of the knee joint were constructed from five divided portions. Cavity formation initiated at multiple sites at E17; among them, the femoropatellar cavity (FPC) was the first. Cavitations of the medial side preceded those of the lateral side. Each cavity connected at E20 when cavitations around the anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were completed. Cavity formation initiated from six portions. In each portion, development proceeded asymmetrically. These results concerning anatomical development of the knee joint using EFIC contribute to a better understanding of the structural feature of the knee joint. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Relaxation and thermalization in the one-dimensional Bose-Hubbard model: A case study for the interaction quantum quench from the atomic limit

NASA Astrophysics Data System (ADS)

Heidrich-Meisner, Fabian; Pollet, Lode; Sorg, Stefan; Vidmar, Lev

2015-03-01

We study the relaxation dynamics and thermalization in the one-dimensional Bose-Hubbard model induced by a global interaction quench. Specifically, we start from an initial state that has exactly one boson per site and is the ground state of a system with infinitely strong repulsive interactions at unit filling. The same interaction quench was realized in a recent experiment. Using exact diagonalization and the density-matrix renormalization-group method, we compute the time dependence of such observables as the multiple occupancy and the momentum distribution function. We discuss our numerical results in the framework of the eigenstate thermalization hypothesis and we observe that the microcanonical ensemble describes the time averages of many observables reasonably well for small and intermediate interaction strength. Moreover, the diagonal and the canonical ensembles are practically identical for our initial conditions already on the level of their respective energy distributions for small interaction strengths. Supported by the DFG through FOR 801 and the Alexander von Humboldt foundation.